The prognostic utility of deceased donor implantation biopsy in determining function and graft survival after kidney transplantation.
Uncertainty remains in the prognostic utility of biopsies of deceased donor kidneys in predicting graft outcomes. We examined implantation biopsies for 730 kidney transplant recipients from 491 deceased donors from 1990 to 2004. The median follow-up time was 5.1 years. Of the 730 transplants, 633 (86.7%) had implantation biopsies (wedge 89.1%). Of these 633, 541 (85.5%) could be assessed for % glomerulosclerosis (GS), interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, and fibrous intimal thickening. Independent risk factors for delayed graft function include regraft, longer cold ischemia time, and DR mismatch, but not donor age. Independent risk factors for worse function at 6 months include regraft, older donor and recipient, female donor and recipient, and rejection. Independent risk factors of graft failure include regraft, older donor age, male recipient, and rejection. Of the histologic scores, arteriolar hyalinosis was independently associated with delayed graft function and graft loss, whereas fibrous intimal thickening was associated with decreased 6-month renal function. Importantly, the degree of GS was not independently associated with outcomes. Therefore, although biopsy evidences of vascular pathologic condition, kidney may contribute meaningfully to the assessment of donor quality but the degree of GS does not.


Evolution in microbes.
This review presents a broad survey of experimental microbial evolution, covering diverse topics including trade-offs, epistasis, fluctuating conditions, spatial dynamics, cooperation, aging, and stochastic switching. Emphasis is placed on examples that highlight key conceptual points or address theoretical predictions. Experimental evolution is discussed from two points of view. First, population trajectories are described as adaptive walks on a fitness landscape, whose genetic structure can be probed by experiments. Second, populations are viewed from a physiological perspective, and their nongenetic heterogeneity is examined. Bringing together these two viewpoints remains a major challenge for the future.


Synthesis of biologically active O-substituted derivatives of 1-[(3, 5-dichloro-2-hydroxyphenyl)sulfonyl]piperidine.
In the present work, a series of 2-O-substituted derivatives of 1-[(3,5-dichloro-2-hydroxy phenyl) sulfonyl]piperidine (5a-j) were synthesized. These derivatives were geared up by the coupling of 3,5-dichloro-2-hydroxy benzenesulfonyl chloride (1) with piperidine (2) under dynamic pH control in aqueous media to form parent compound 1-[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]piperidine (3), followed by the substitution at oxygen atom with different electrophiles (4a-j) in the presence of sodium hydride (NaH) and dimethyl formamide (DMF) to give a series of O-substituted derivatives of sulfonamides bearing piperidine nucleus 5a-j. The synthesized O-substituted sulfonamides were spectrally characterized. The bioactivity of all the synthesized compounds were evaluated against lipoxygenase (LOX), acetylcholinesterae (AChE) and butyrylcholinesterase (BChE) enzymes and found to be having talented activity against butyrylcholinesterase enzyme.


Type of terrain and infant and young child feeding practices: cross-sectional study findings on children below 2 years of age from northern Bangladesh.
Optimal feeding practices are vital for the subsistence, adequate nutrition, physical growth and mental development of infants and young children. This study aimed to examine the prevalence of core infant and young child feeding (IYCF) indicators and their associations with the type of terrain, that is, geographical area or zone among the beneficiaries of a large-scale nutrition programme, Suchana, being carried out in the northern part of rural Bangladesh. A cross-sectional study was conducted from November 2016 to February 2017 in Sylhet and Moulvibazar districts of Sylhet Division, Bangladesh. Data pertaining to 5440 children aged below 24 months were analysed for this study. Univariate analysis was carried out to establish the prevalence of the indicators; selected variables were subjected to multiple regression model to identify independent relationships between the IYCF indicators and the type of terrain stratified as plain land, hilly area, flash-flood prone area and haor (wetland). In logistic regression analysis, flash-flood prone areas were significantly associated with higher exclusive breast feeding (1.92, 95% CI 1.12 to 3.30; p=0.019), minimum meal frequency (1.45, 95% CI 1.07 to 1.97; p=0.018) and minimum dietary diversity (1.63, 95% CI 1.01 to 2.63; p=0.046) compared with plain land. Moreover, hilly areas were associated with significantly lower introduction of solid, semisolid or soft foods (0.39, 95% CI 0.18 to 0.82; p=0.013) compared with plain land. The observed prevalence of the indicators can be set as benchmark while prioritising interventions aimed at improving IYCF practices among underprivileged families residing in different types of rural setting in Bangladesh.


Access to orthopedic care for children with medicaid versus private insurance in California.
To compare the availability of timely orthopedic care to a child with a fractured arm insured by Medi-Cal (California state Medicaid) and by private insurance. Fifty randomly chosen offices of orthopedic surgeons were telephoned with the following scenario: "My 10-year-old son broke his arm last week during a vacation" followed by a request for an appointment that week. Each office was called twice with an identical script except for insurance status: once with Medi-Cal and once with private insurance. All 50 offices offered an appointment to see the child with private insurance within 7 days. Only 1 of the same 50 offices offered an appointment to see the child with Medi-Cal within 7 days. Of the offices that would not see a child with Medi-Cal, 87% were unable to recommend an orthopedic office that accepted Medi-Cal. Timely access to orthopedic care was available in 100% of offices polled to a child with private insurance versus in 2% of offices to a child with Medi-Cal. This is a significant difference. Lack of timely orthopedic care may result in poor outcome, ie, if a fracture is not properly aligned in the first few weeks, a permanent deformity may result. Although causation cannot be established from this study, we suspect that Medi-Cal reimbursement rates below the cost of office overhead may be of significance. Although federal guidelines require that payments must be sufficient to enlist enough providers so that services to Medi-Cal recipients are available to the same extent as those available to the general population, this study finds that that children with Medi-Cal insurance have significantly less access to timely orthopedic care.


Antibody-drug conjugates harboring a kinesin spindle protein inhibitor with immunostimulatory properties.
Antibody-drug conjugates (ADCs) are used to target cancer cells by means of antibodies directed to tumor-associated antigens, causing the incorporation of a cytotoxic payload into target cells. Here, we characterized the mode of action of ADC costing of a TWEAKR-specific monoclonal antibody conjugated to a small molecule kinesin spindle protein (KSP) inhibitor (KSPi). These TWEAKR-KSPi-ADCs showed strong efficacy in a TWEAKR expressing CT26 colon cancer model in mice. TWEAKR-KSPi-ADCs controlled the growth of CT26 colon cancers in immunodeficient as well as in immunocompetent mice. However, when treated with suboptimal doses, TWEAKR-KSPi-ADCs were still active in immunocompetent but not in immunodeficient mice, indicating that TWEAKR-KSPi-ADCs act - in addition to the cytotoxic mode of action - through an immunological mechanism. Indeed, in vitro experiments performed with a cell-permeable small molecule KSPi closely related to the active payload released from the TWEAKR-KSPi-ADCs revealed that KSPi was capable of stimulating several hallmarks of immunogenic cell death (ICD) on three different human cancer cell lines: cellular release of adenosine triphosphate (ATP) and high mobility group B1 protein (HMGB1), exposure of calreticulin on the cell surface as well as a transcriptional type-I interferon response. Further, in vivo experiments confirmed that treatment with TWEAKR-KSPi-ADCs activated immune responses via enhancing the infiltration of CD4+ and CD8+ T lymphocytes in tumors and the local production of interferon-γ, interleukin-2, and tumor necrosis factor-α. In conclusion, the antineoplastic effects of TWEAKR-KSPi-ADCs can partly be attributed to its ICD-stimulatory properties.


Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort.
Nutritional factors are essential for the functioning of the immune system and could therefore play a role in COVID-19 but evidence is needed. Our objective was to study the associations between diet and the risk of SARS-CoV-2 infection in a large population-based sample. Our analyses were conducted in the French prospective NutriNet-Santé cohort study (2009-2020). Seroprevalence of anti-SARS-CoV-2 antibodies was assessed by ELISA on dried blood spots. Dietary intakes were derived from repeated 24 h dietary records (at least 6) in the two years preceding the start of the COVID-19 pandemic in France (February 2020). Multi-adjusted logistic regression models were computed. A total of 7766 adults (70.3% women, mean age: 60.3 years) were included, among which 311 were positive for anti-SARS-CoV-2 antibodies. Dietary intakes of vitamin C (OR for 1 SD=0.86 (0.75-0.98), P=0.02), vitamin B9 (OR=0.84 (0.72-0.98), P=0.02), vitamin K (OR=0.86 (0.74-0.99), P=0.04), fibers (OR=0.84 (0.72-0.98), P=0.02), and fruit and vegetables (OR=0.85 (0.74-0.97), P=0.02) were associated to a decreased probability of SARS-CoV-2 infection while dietary intakes of calcium (OR=1.16 (1.01-1.35), P=0.04) and dairy products (OR=1.19 (1.06-1.33), P=0.002) associated to increased odds. No association was detected with other food groups or nutrients or with the overall diet quality. Higher dietary intakes of fruit and vegetables and, consistently, of vitamin C, folate, vitamin K and fibers were associated with a lower susceptibility to SARS-CoV-2 infection. Beyond its established role in the prevention of non-communicable diseases, diet could therefore also contribute to prevent some infectious diseases such as COVID-19.


Nonmedical Use of Benzodiazepines among Immigrant and Native-Born Adolescents in Spain: National Trends and Related Factors.
the nonmedical use of prescribed medications among adolescents has increased significantly in recent years. We aimed to identify the patterns of benzodiazepine nonmedical use and its evolution during the decade 2006-2016 among immigrant and native-born adolescent populations. we used individualized secondary data retrieved from the 2006-2016 Spanish State Survey on Drug Use in Secondary Education (ESTUDES) of the school-aged population. Using logistic multivariate regression models, we estimated the independent effect of each of these variables on nonmedical use. Two models were generated: one for immigrant adolescents and one for native-born adolescents. during the decade 2006-2016, 2.81% of native-born and 3.36% of immigrant adolescent students made nonmedical use of benzodiazepines. Gender and socioeconomic status were found to be related to the nonmedical use of benzodiazepines. Consumption of illegal psychoactive substances, other than marijuana, was the variable of greatest value (aOR = 6.00, 95% CI 3.89-9.27). Perceived risks and drug availability were found to be predictors for the nonmedical use of benzodiazepines in both immigrant and native-born adolescents. in Spain, patterns of benzodiazepine nonmedical use among immigrant and native-born adolescents are similar. The results of this study refute certain stereotypes related to consumption of substances among immigrant adolescents, identifying them as a risk group.


Understanding solvent effects in the selective conversion of fructose to 5-hydroxymethyl-furfural: a molecular dynamics investigation.
Selective conversion of fructose to 5-hydroxymethyl-furfural (HMF) involves the participation of high-boiling solvents like dimethyl sulfoxide (DMSO). In order to replace DMSO with low-boiling solvents, it is imperative that we understand the effect of DMSO solvation in protecting (i) HMF from rehydration and humins formation reactions and (ii) fructose from side reactions, other than its dehydration to HMF. In the present work, molecular dynamics simulations of HMF and fructose in water and in water-DMSO mixtures are carried out using the OPLS-AA force field. Radial pair distribution functions, coordination numbers and the hydrogen-bond network between the HMF/fructose molecule and the solvent molecules are analysed. The local 3-dimensional picture of the arrangement of solvent molecules around the solute, which cannot be accessed from pair distribution functions, is also computed. We show preferential coordination of DMSO around HMF and explain how this could provide a shielding effect to the HMF molecule, thus protecting it from further rehydration to levulinic acid and formic acid and from humins formation. In the case of fructose, the presence of DMSO also reduces the number of water molecules in the immediate vicinity of fructose. Though fewer water molecules coordinate around fructose, they are bound strongly to it. Analysis of the local 3-dimensional arrangement of DMSO molecules suggests that it protects the fructose molecule from side reactions that would lead to condensation or reversion products. However, the presence of DMSO molecules does not hamper the water molecules coming into contact with the oxygen atom of the hydroxyl groups of fructose, which is required for a proton transfer from water to fructose, to initiate the dehydration reaction to HMF.


Accomplishments in 2008 in the treatment of metastatic pancreatic cancer.
Overview of the DiseaseIncidencePrognosisCurrent Treatment StandardsCytotoxic TherapyTargeted TherapySalvage TherapyAccomplishments or Lack of AccomplishmentsTherapySalvage TherapyBiomarkersApplication of the AccomplishmentsFuture DirectionsCurrent Basic ResearchOngoing Clinical StudiesMajor Obstacles to Progress in Drug DevelopmentGemcitabine PlatformChoice of Molecular TargetsPatient Selection.


Health expenditures in New York City, 1983.
HIGHLIGHTS OF THE STUDY. Health expenditures in New York City totalled roughly $15.7 billion in 1983. Those expenditures represented 13.5 percent of the gross city product. Expenditures for personal health care services amounted to more than $1,900 per city resident. Despite comparatively high levels of health expenditures in New York City, such expenditures have risen much less dramatically over time than health expenditures nationally; from 1976 to 1983, city expenditures increased by 74.6 percent, compared with a national increase of 137.7 percent. More than one half (55.3%) of health expenditures in the city were accounted for by public funds. Nearly 50 percent of personal care expenditures were associated with the delivery of hospital services, for which expenditures totalled $6.9 billion. Fifty-five percent of Medicaid hospital outlays and 86 percent of Medicare hospital outlays went to private sector hospitals. More than $400 per capita was spent on physicians' services in New York City in 1983. Public sources of funds accounted for more than 80 percent of the $1.7 billion in long term care services expenditures; this contrasts with a much smaller proportion of public funding for such services nationally. More details on health expenditures in New York City follow. Data sources, definitions, study methods, and limitations are described in an appendix to this report.


Urea in aqueous solution studied by quantum mechanical charge field-molecular dynamics (QMCF-MD).
This work presents a quantum mechanical charge field-molecular dynamics (QMCF-MD) simulation of urea in dilute aqueous solution. Detailed data for structure and dynamics are provided and compared to previous works of other groups. Radial and angular distributions are employed, as well as higher degree spatial investigations, two-dimensional particle mapping, volume maps and the previously proposed SLICE formalism. Information on dynamical properties are presented in the form of hydrogen bond correlation functions and mean lifetime analysis based on weighted Voronoi decomposition. Dihedral and tilt/theta angle distributions substantiate the previous findings of other groups, that urea is far from being planar within aqueous solution. In addition to the analysis of the complete hydration shell, several specific regions of hydration have been identified, for which individual analysis has been performed in terms of hydrogen bond lifetime correlation functions and re-orientational times. A decomposition study based on Laguerre tessellation further investigates the structure and dynamics of the individual hydration layers. It is found that urea does not show properties found in the case of typical structure breaking agents, such as Rb(+) or Cs(+), which is in accordance with spectroscopic data of Rezus and Bakker.


Minimizing the risk of chronic allograft nephropathy.
Chronic allograft nephropathy, now defined as interstital fibrosis and tubular atrophy not otherwise specified, is a near universal finding in transplant kidney biopsies by the end of the first decade posttransplantation. After excluding death with functioning graft, caused by cardiovascular disease or malignancy, chronic allograft nephropathy is the leading cause of graft failure. Original assumptions were that this was not a modifiable process but inexorable, likely due to past kidney injuries. However, newer understandings suggest that acute or subacute processes are involved, and with proper diagnosis, appropriate interventions can be instituted. Our method involved a review of the primary and secondary prevention trials in calcineurin inhibitor withdrawal. Some of the more important causes of progressive graft deterioration include subclinical cellular or humoral rejection, and chronic calcineurin inhibitor toxicity. Early graft biopsy, assessment of histology, and changes in immunosuppression may be some of the most important measures available to protect graft function. The avoidance of clinical inertia in pursuing subtle changes in graft function is critical. Modification in maintenance immunosuppression may benefit many patients with early evidence of graft deterioration.


The involvement of ACO3 protein in diabetic retinopathy through the PI3k/Akt signaling pathway.
Diabetic retinopathy (DR) is one of the most common complications of diabetic microvascular disease and its pathogenesis is complicated. The PI3k/Akt signaling pathway plays an important role in the angiogenesis of DR. To explore the molecular mechanisms of the ACO3 protein and related proteins in DR, in order to provide a scientific theoretical basis for the clinical treatment of this disease. A DR rat model was used in this study. One group (anti-ACO3 group, n = 10) was injected with protein ACO3 antagonist; the 2nd study group (the DR group, n = 10) was injected with the same amount of normal saline; the control group (n = 10) did not undergo any procedures. We used hematoxylin and eosin (H&E) staining to observe the pathological features of the eye tissues. Immunohistochemistry was used to analyze the expression of ACO3 and AKT. Western blot was used to analyze the expression of ANGPT1, ANGPT4 and KDR; reverse transcription polymerase chain reaction (RT-PCR) was used to assess the mRNA expression of AKT, ACO3 and SMOX in the eye tissues of the rats. In the anti-ACO3 group, the results of H&E staining showed that there was a decrease in retinal edema and no obvious abnormality in the blood vessels. The immunohistochemistry analysis of proteins proved that ACO3 and AKT were strongly expressed in the DR group. The western blot analysis of ANGPT1, ANGPT4 and KDR expression showed that in the DR group, the expression of all 3 proteins was higher than in the anti-ACO3 group, and much higher than in the control group. The mRNA expression of AKT, ACO3 and SMOX was strong in the DR group, but decreased in the anti-ACO3 group.


Genomic analysis of siderophore β-hydroxylases reveals divergent stereocontrol and expands the condensation domain family.
Genome mining of biosynthetic pathways streamlines discovery of secondary metabolites but can leave ambiguities in the predicted structures, which must be rectified experimentally. Through coupling the reactivity predicted by biosynthetic gene clusters with verified structures, the origin of the β-hydroxyaspartic acid diastereomers in siderophores is reported herein. Two functional subtypes of nonheme Fe(II)/α-ketoglutarate-dependent aspartyl β-hydroxylases are identified in siderophore biosynthetic gene clusters, which differ in genomic organization-existing either as fused domains (IβHAsp) at the carboxyl terminus of a nonribosomal peptide synthetase (NRPS) or as stand-alone enzymes (TβHAsp)-and each directs opposite stereoselectivity of Asp β-hydroxylation. The predictive power of this subtype delineation is confirmed by the stereochemical characterization of β-OHAsp residues in pyoverdine GB-1, delftibactin, histicorrugatin, and cupriachelin. The l-threo (2S, 3S) β-OHAsp residues of alterobactin arise from hydroxylation by the β-hydroxylase domain integrated into NRPS AltH, while l-erythro (2S, 3R) β-OHAsp in delftibactin arises from the stand-alone β-hydroxylase DelD. Cupriachelin contains both l-threo and l-erythro β-OHAsp, consistent with the presence of both types of β-hydroxylases in the biosynthetic gene cluster. A third subtype of nonheme Fe(II)/α-ketoglutarate-dependent enzymes (IβHHis) hydroxylates histidyl residues with l-threo stereospecificity. A previously undescribed, noncanonical member of the NRPS condensation domain superfamily is identified, named the interface domain, which is proposed to position the β-hydroxylase and the NRPS-bound amino acid prior to hydroxylation. Through mapping characterized β-OHAsp diastereomers to the phylogenetic tree of siderophore β-hydroxylases, methods to predict β-OHAsp stereochemistry in silico are realized.


Optimization-Based Image Reconstruction From Low-Count, List-Mode TOF-PET Data.
We investigate an optimization-based approach to image reconstruction from list-mode data in digital time-of-flight (TOF) positron emission tomography (PET) imaging. In the study, the image to be reconstructed is designed as a solution to a convex, non-smooth optimization program, and a primal-dual algorithm is developed for image reconstruction by solving the optimization program. The algorithm is first applied to list-mode TOF-PET data of a typical count level from physical phantoms and a human subject. Subsequently, we explore the algorithm's potential for image reconstruction in low-dose and/or fast TOF-PET imaging of practical interest by applying the algorithm to list-mode TOF-PET data of different, low-count levels from the same physical phantoms and human subject. Visual inspection and quantitative-metric analysis reveal that the optimization reconstruction approach investigated can yield images with enhanced spatial and contrast resolution, suppressed image noise, and increased axial volume coverage over the reference images obtained with a standard clinical reconstruction algorithm especially for low-dose TOF-PET data. The optimization-based reconstruction approach can be exploited for yielding insights into potential quality upper bound of reconstructed images in, and design of scanning protocols of, TOF-PET imaging of practical significance.


PBL implementation of Kathmandu University Curriculum - Is It Quo Vadis?
The history of the implementation of PBL which started in 1978 is long and there have been many ups and downs in the process of getting it to work. Of course there are many reasons for this, starting with the fact that basically it is a method of learning of medicine that is being tried out in various parts of the world. What is envisaged by KU is a hybrid form of the process to be implemented for the MBBS course that KUSMS conducts at its campus at Chaukot, Kavre and at its seven affiliated medical colleges. Various points regarding this are discussed in this article. The information provided in the MBBS curriculum of KU was analysed and comments made there on. The syllabi of IoM, BPKIHS and PAHS were also referred to, to note the existing differences.


From Gaudin Integrable Models to d-Dimensional Multipoint Conformal Blocks.
In this work, we initiate an integrability-based approach to multipoint conformal blocks for higher-dimensional conformal field theories. Our main observation is that conformal blocks for N-point functions may be considered as eigenfunctions of integrable Gaudin Hamiltonians. This provides us with a complete set of differential equations that can be used to evaluate multipoint blocks.


The C. elegans Intestine As a Model for Intercellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis at the Single-cell Level: Labeling by Antibody Staining, RNAi Loss-of-function Analysis and Imaging.
Multicellular tubes, fundamental units of all internal organs, are composed of polarized epithelial or endothelial cells, with apical membranes lining the lumen and basolateral membranes contacting each other and/or the extracellular matrix. How this distinctive membrane asymmetry is established and maintained during organ morphogenesis is still an unresolved question of cell biology. This protocol describes the C. elegans intestine as a model for the analysis of polarized membrane biogenesis during tube morphogenesis, with emphasis on apical membrane and lumen biogenesis. The C. elegans twenty-cell single-layered intestinal epithelium is arranged into a simple bilaterally symmetrical tube, permitting analysis on a single-cell level. Membrane polarization occurs concomitantly with polarized cell division and migration during early embryogenesis, but de novo polarized membrane biogenesis continues throughout larval growth, when cells no longer proliferate and move. The latter setting allows one to separate subcellular changes that simultaneously mediate these different polarizing processes, difficult to distinguish in most polarity models. Apical-, basolateral membrane-, junctional-, cytoskeletal- and endomembrane components can be labeled and tracked throughout development by GFP fusion proteins, or assessed by in situ antibody staining. Together with the organism's genetic versatility, the C. elegans intestine thus provides a unique in vivo model for the visual, developmental, and molecular genetic analysis of polarized membrane and tube biogenesis. The specific methods (all standard) described here include how to: label intestinal subcellular components by antibody staining; analyze genes involved in polarized membrane biogenesis by loss-of-function studies adapted to the typically essential tubulogenesis genes; assess polarity defects during different developmental stages; interpret phenotypes by epifluorescence, differential interference contrast (DIC) and confocal microscopy; quantify visual defects. This protocol can be adapted to analyze any of the often highly conserved molecules involved in epithelial polarity, membrane biogenesis, tube and lumen morphogenesis.


[An unusual displacement fracture of the 1st metacarpal bone. Apropos of a case reviewed after 3 years].
An unusual fracture of the base of the first metacarpal with in contrast with Bennett's fracture displacement of the thumb and avulsion of the Abductor Pollicis Longus tendon is described after a "Rugby" trauma. Immediate repair and stabilization of the injured structures followed by specific rehabilitation, produced a satisfactory result with normal function of the thumb three years after the injury.


[Prognosis analysis of surgical treatment for cancer of stomach fundus and cardia with invasion to body and tail of the pancreas].
To investigate the prognostic factors of surgical treatment for the cancer of stomach fundus and cardia with invasion to body and tail of the pancreas. A total of 135 patients with cancer of stomach fundus and cardia invading body and tail of the pancreas undergone surgical treatment were enrolled in this study. Twenty of them underwent laparotomy, while 115 underwent gastrectomy with pancreaticosplenectomy, even combined with the resection of other organs for macroscopic invasion to adjacent organs during surgery. The 3-,5-year survival rates, morbidity of postoperative complications and mortality were followed up. The prognostic factors were evaluated by univariate and multivariate analyses. The median survival time of the patients undergone laparotomy was 4.7 months, of patients treated by gastrectomy combined with pancreaticosplenectomy was 30.5 months,and the difference was significant (chi(2)=403.8, P<0.01). The cumulative 3- and 5-year survival rates of the patients treated by gastrectomy combined with pancreaticosplenectomy were 48.3% and 26.6% respectively. Univariate analysis revealed that significant differences in prognosis of 115 patients undergone combined resection were demonstrated for the following factors: maximal dimension of tumor, macroscopic type, extent of lymph node metastasis according to the Japanese classification, No.10 or No.11 lymph node metastasis,curability and number of invaded organs.And histological depth of invasion, extent of lymph node metastasis according to the Japanese classification, number of invaded organs and curability were significant prognostic factors, examined as variables by multivariate analysis (Cox's proportional hazard model, forward stepwise selection LR method). The postoperative complication rate and mortality of 135 patients were 20.0% and 3.5% respectively. For cancer located in stomach fundus and cardia with limited invasion to distal pancreas, gastrectomy combined with pancreaticosplenectomy should be performed to improve long-term outcomes. Best long-term survival outcomes would be attained if there are no lymph node metastases, or no incurable factors, or no other organ invasions.


Exercise training normalizes elevated firing rate of hypothalamic presympathetic neurons in heart failure rats.
Exercise training (ExT) normalizes elevated sympathetic nerve activity in heart failure (HF), but the underlying mechanisms are not well understood. In this study, we examined the effects of 3 wk of ExT on the electrical activity of the hypothalamic presympathetic neurons in the brain slice of HF rats. HF rats were prepared by ligating the left descending coronary artery. The electrophysiological properties of paraventricular nucleus neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) were examined using the slice patch-clamp technique. The neuronal firing rate was elevated in HF rats, and ExT induced a reduction in the firing rate ( P < 0.01). This ExT-induced decrease in the firing rate was associated with an increased frequency of spontaneous and miniature inhibitory postsynaptic current (IPSCs; P < 0.05). There was no significant change in excitatory postsynaptic current. Replacing Ca2+ with Mg2+ in the recording solution reduced the elevated IPSC frequency in HF rats with ExT ( P < 0.01) but not in those without ExT, indicating an increase in the probability of GABA release. In contrast, ExT did not restore the reduced GABAA receptor-mediated tonic inhibitory current in HF rats. A GABAA receptor blocker (bicuculline, 20 μM) increased the firing rate in HF rats with ExT ( P < 0.01) but not in those without ExT. Collectively, these results show that ExT normalized the elevated firing activity by increasing synaptic GABA release in PVN-RVLM neurons in HF rats. Our findings provide a brain mechanism underlying the beneficial effects of ExT in HF, which may shed light on the pathophysiology of other diseases accompanied by sympathetic hyperactivation.


A distinct mechanism for coactivator versus corepressor function by histone methyltransferase G9a in transcriptional regulation.
Histone methyltransferase G9a has been understood primarily as a corepressor of gene expression, but we showed previously that G9a positively regulates nuclear receptor-mediated transcription in reporter gene assays. Here, we show that endogenous G9a contributes to the estradiol (E(2))-dependent induction of some endogenous target genes of estrogen receptor (ER)α in MCF-7 breast cancer cells while simultaneously limiting the E(2)-induced expression of other ERα target genes. Thus, G9a has a dual and selective role as a coregulator for ERα target genes. The ERα binding regions associated with the pS2 gene, which requires G9a for E(2)-induced expression, are transiently occupied by G9a at 15 min after beginning E(2) treatment, suggesting that G9a coactivator function is by direct interaction with ERα target genes. Transient reporter gene assays with deletion mutants of G9a demonstrated that domains previously associated with the corepressor functions of G9a (C-terminal methyltransferase domain, ankyrin repeat domain, and cysteine-rich domain) were unnecessary for G9a coactivator function in ERα-mediated transcription. In contrast, the N-terminal domain of G9a was necessary and sufficient for enhancement of ERα-mediated transcription and for E(2)-induced occupancy of G9a on ERα binding sites associated with endogenous target genes of ERα. In addition to a previously identified activation domain, this region contains a previously uncharacterized ligand-dependent ERα binding function, indicating how G9a is recruited to the target genes. Therefore, the coactivator and corepressor functions of G9a involve different G9a domains and different molecular mechanisms.


What works in implementation of integrated care programs for older adults with complex needs? A realist review.
A realist review of the evaluative evidence was conducted on integrated care (IC) programs for older adults to identify key processes that lead to the success or failure of these programs in achieving outcomes such as reduced healthcare utilization, improved patient health, and improved patient and caregiver experience. International academic literature was searched in 12 indexed, electronic databases and gray literature through internet searches, to identify evaluative studies. Inclusion criteria included evaluative literature on integrated, long-stay health and social care programs, published between January 1980 and July 2015, in English. Data were extracted on the study purpose, period, setting, design, population, sample size, outcomes, and study results, as well as explanations of mechanisms and contextual factors influencing outcomes. A total of 65 articles, representing 28 IC programs, were included in the review. Two context-mechanism-outcome configurations (CMOcs) were identified: (i) trusting multidisciplinary team relationships and (ii) provider commitment to and understanding of the model. Contextual factors such as strong leadership that sets clear goals and establishes an organizational culture in support of the program, along with joint governance structures, supported team collaboration and subsequent successful implementation. Furthermore, time to build an infrastructure to implement and flexibility in implementation, emerged as key processes instrumental to success of these programs. This review included a wide range of international evidence, and identified key processes for successful implementation of IC programs that should be considered by program planners, leaders and evaluators.


Partial characterization of two lymphocyte-specific natural autoantibodies isolated from newborn mice.
The early antibody-repertoire is mainly composed of multi- and polyreactive IgM autoantibodies. Some of them (about 10%) also react with cell surface antigens. It is supposed that these latter antibodies promote--particularly under the maturation of the immune system--the expansion of different lymphocyte populations and subpopulations, namely the filling of the secondary lymphoid organs by immunocompetent cells. In order to verify this hypothesis we established hybridoma clones from newborn Balb/c mice. Almost all IgM antibodies produced by these hybridomas (94%) were found to be polyreactive, but only two--the 4/5 and the 8/8--react with cell surface structures. The 4/5 IgM recognizes a glicerin-phosphathydil-inositol (GPI)-anchored membrane component expressed on the early thymocytes. The 8/8 antibody reacts with resting splenic B lymphocytes as well as B and T cell blasts via an about 40 kD protein. They do not influence the spontaneous or the mitogen induced proliferation of the lymphocytes. Therefore we cannot confirm the hypothesis that increase of the expansion of peripheral lymphocytes would be the main function of these neonatal natural autoantibodies.


Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging.
To study the validity of both rheumatological and orthodontic examinations and ultrasound (US) as screening methods for early diagnosis of TMJ arthritis against the gold standard MRI. Thirty consecutive juvenile idiopathic arthritis (JIA) patients were included in this pilot study. Rheumatological and orthodontic examinations as well as US were performed within 1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast enhancement of synovium or bone were considered signs of active arthritis on MRI. A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ involvement on MRI. This was associated with condylar deformity in 9/19 (47%) patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients, respectively, as having no signs of inflammation. The best predictor for active arthritis on MRI was a reduced maximum mouth opening. None of the methods tested was able to reliably predict the presence or absence of MRI-proven inflammation in the TMJ in our cohort of JIA patients. US was the least useful of all methods tested to exclude active TMJ arthritis.


Glomerular filtration rate after alpha-radioimmunotherapy with 211At-MX35-F(ab')2: a long-term study of renal function in nude mice.
Besides bone marrow, the kidneys are often dose-limiting organs in internal radiotherapy. The effects of high-linear energy transfer (LET) radiation on the kidneys after alpha-radioimmunotherapy (alpha-RIT) with the alpha-particle emitter, (211)At, were studied in nude mice by serial measurements of the glomerular filtration rate (GFR). The renal toxicity was evaluated at levels close to the dose limit for the bone marrow and well within the range for therapeutic efficacy on tumors. Astatinated MX35-F(ab')(2) monoclonal antibodies were administered intravenously to nude mice. Both non-tumor-bearing animals and animals bearing subcutaneous xenografts of the human ovarian cancer cell line, OVCAR-3, were used. The animals received approximately 0.4, 0.8, or 1.2 MBq in one, two, or three fractions. The mean absorbed doses to the kidneys ranged from 1.5 to 15 Gy. The renal function was studied by serial GFR measurements, using plasma clearance of (51)Cr-EDTA, up to 67 weeks after the first astatine injection. A dose-dependent effect on GFR was found and at the time interval 8-30 weeks after the first administration of astatine, the absorbed doses causing a 50% decrease in GFR were 16.4 +/- 3.3 and 14.0 +/- 4.1 Gy (mean +/- SEM), tumor- and non-tumor-bearing animals, respectively. The reduction in GFR progressed with time, and at the later time interval, (31-67 weeks) the corresponding absorbed doses were 7.5 +/- 2.4 and 11.3 +/- 2.3 Gy, respectively, suggesting that the effects of radiation on the kidneys were manifested late. Examination of the kidney sections showed histologic changes that were overall subdued. Following alpha-RIT with (211)At-MX35-F(ab')(2) at levels close to the dose limit of severe myelotoxicity, the effects found on renal function were relatively small, with only minor to moderate reductions in GFR. These results suggest that a mean absorbed dose to the kidneys of approximately 10 Gy is acceptable, and that the kidneys would not be the primary dose-limiting organ in systemic alpha-RIT when using (211)At-MX35-F(ab')(2).


Search for improved host architectures: application of de novo structure-based design and high-throughput screening methods to identify optimal building blocks for multidentate ethers.
This paper presents a computational approach to the deliberate design of improved host architectures. The approach, which involves the use of computer-aided design software, is illustrated by application to cation hosts containing multiple aliphatic ether oxygen binding sites. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential bidentate building block structures. Enhanced cation binding affinity can be achieved when highly organized building blocks are used to construct macrocyclic hosts.


Molecular dynamics in protein-single stranded DNA complexes. Two distinct nucleoside mobilities in poly(deoxythymidylic acid)-gene 5 protein complexes.
A set of differently spin labeled (dT)n is used to evaluate thymidine dynamics and some of the structural features in a (dT)n-gene 5 protein complex. ESR evidence is presented that only one of the four thymidine residues bound in the DNA binding channel shows strong immobilization, whereas the other three display significant mobility of the order of nanoseconds. It is hypothesized that the accessability of such mobile bases could be critical to the recognition of the (dT)n-gene 5 protein complex in auxiliary interactions with other proteins and competitive DNAs.


Inhibition of farnesyl pyrophosphate synthase prevents angiotensin II-induced cardiac fibrosis in vitro.
Farnesyl pyrophosphate synthase (FPPS)-catalysed isoprenoid intermediates are important for the activation of Ras homologue gene family, member A (RhoA) in angiotensin (Ang) II-induced cardiac fibrosis. This study was designed to investigate the specific role of FPPS in the development of cardiac fibrosis. We demonstrated that FPPS expression was elevated in both in-vivo and in-vitro models of Ang II-mediated cardiac fibrosis. FPPS inhibition by zolendronate and FPPS knock-down by a silencing lentivirus decreased the expression of cardiac fibrosis marker genes, including collagen I, collagen III and transforming growth factor (TGF)-β1. FPPS inhibition was reversed by geranylgeraniol (GGOH) and mimicked by RhoA knock-down with siRhoA. The antagonistic effect of GGOH on the zolendronate-mediated modulation of RhoA activation in Ang II-stimulated cardiac fibroblasts was demonstrated by a pull-down assay. Furthermore, FPPS knock-down also prevented RhoA activation by Ang II in vitro. In conclusion, FPPS and RhoA may be part of a signalling pathway that plays an important role in Ang II-induced cardiac fibrosis in vitro.


Ligand Design in Ligand-Protected Gold Nanoclusters.
The design of surface ligands is crucial for ligand-protected gold nanoclusters (Au NCs). Besides providing good protection for Au NCs, the surface ligands also play the following two important roles: i) as the outermost layer of Au NCs, the ligands will directly interact with the exterior environment (e.g., solvents, molecules and cells) influencing Au NCs in various applications; and ii) the interfacial chemistry between ligands and gold atoms can determine the structures, as well as the physical and chemical properties of Au NCs. A delicate ligand design in Au NCs (or other metal NCs) needs to consider the covalent bonds between ligands and gold atoms (e.g., gold-sulfur (Au-S) and gold-phosphorus (Au-P) bond), the physics forces between ligands (e.g., hydrophobic and van der Waals forces), and the ionic forces between the functional groups of ligands (e.g., carboxylic (COOH) and amine group (NH2 )); which form the underlying chemistry and discussion focus of this review article. Here, detailed discussions on the effects of surface ligands (e.g., thiolate, phosphine, and alkynyl ligands; or hydrophobic and hydrophilic ligands) on the synthesis, structures, and properties of Au NCs; highlighting the design principles in the surface engineering of Au NCs for diverse emerging applications, are provided.


Screening for proteinuria in patients with hypertension or diabetes mellitus.
Proteinuria is an early indication of renal disease. This study was conducted to evaluate the usefulness of dipstick urinalysis in patients with chronic diseases including hypertension and diabetes mellitus. At a university family practice center, patients without urinary tract disorders underwent dipstick urinalysis. Of the 796 patients evaluated, increased proteinuria, possibly indicating early renal disease, was detected in 4% of healthy patients, 16% of patients with hypertension, 29% of patients with diabetes, and 53% of patients with both hypertension and diabetes. A higher incidence of proteinuria was found among African American patients with hypertension or diabetes or both than among white patients. Regular dipstick evaluation for proteinuria may be indicated in patients with hypertension or diabetes mellitus or both, particularly African American patients with these disorders.


Role of lysine 173 in heparin binding to heparin cofactor II.
Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits alpha-thrombin in a reaction that is dramatically enhanced by heparin and other glycosaminoglycans/polyanions. We investigated the glycosaminoglycan binding site in HC by: (i) chemical modification with pyridoxal 5'-phosphate (PLP) in the absence and presence of heparin and dermatan sulfate; (ii) molecular modeling; and (iii) site-directed oligonucleotide mutagenesis. Four lysyl residues (173, 252, 343, and 348) were protected from modification by heparin and to a lesser extent by dermatan sulfate. Heparin-protected PLPHC retained both heparin cofactor and dermatan sulfate cofactor activity while dermatan sulfate-protected PLPHC retained some dermatan sulfate cofactor activity and little heparin cofactor activity. Molecular modeling studies revealed that Lys173 and Lys252 are within a region previously shown to contain residues involved in glycosaminoglycan binding. Lys343 and Lys348 are distant from this region, but protection by heparin and dermatan sulfate might result from a conformational change following glycosaminoglycan binding to the inhibitor. Site-directed mutagenesis of Lys173 and Lys343 was performed to further dissect the role of these two regions during HC-heparin and HC-dermatan sulfate interactions. The Lys343----Asn or Thr mutants had normal or only slightly reduced heparin or dermatan sulfate cofactor activity and eluted from heparin-Sepharose at the same ionic strength as native recombinant HC. However, the Lys173----Gln or Leu mutants had greatly reduced heparin cofactor activity and eluted from heparin-Sepharose at a significantly lower ionic strength than native recombinant HC but retained normal dermatan sulfate cofactor activity. Our results demonstrate that Lys173 is involved in the interaction of HC with heparin but not with dermatan sulfate, whereas Lys343 is not critical for HC binding to either glycosaminoglycan. These data provide further evidence for the determinants required for glycosaminoglycan binding to HC.


Seroprevalence and risk factors for peste des petits ruminants in sheep and goats in Djibouti.
Despite the occurrence of peste des petits ruminants (PPR) in all other countries in the Horn of Africa, which engage in free animal movement, to date, PPR has not been reported in Djibouti. The objective of this study was to estimate the seroprevalence of PPR and its associated risk factors in sheep and goats in that country. A cross-sectional method was used with proportional sampling to allocate the number of small ruminants to be sampled from each of the country's regions (Ali Sabieh, Arta, Dikhil, Djibouti, Obock and Tadjourah). From a total of 1,516 serum samples tested, using a competitive enzyme-linked immunosorbent assay (cELISA), 91 were positive, with an overall 6% (95% confidence interval [CI] = 4.8-7.2) prevalence of antibodies to the PPR virus (PPRV). Antibodies to PPRV were detected in small ruminants from all the regions, excluding Obock. Seroprevalence was highest in the Tadjourah region (8.92%), whereas the lowest prevalence was observed in the Djibouti region (1.28%). The species, age and sex of the animals and the herd size were identified as risk factors for PPR seropositivity. The risk of goats testing positive for PPRV antibodies was2.95 (CI = 1.39-6.35) times that of sheep. Moreover, the risk of animals younger than two years testing positive for PPRV antibodies was 2.29 (CI = 1.47-3.56) times that of animals older than two years. Similarly, it was shown that female animals were more frequently infected (odds ratio [OR] = 3.82; CI = 1.51 to 9.67) than their male counterparts. In addition, small ruminants from small herds/flocks were more likely to be seropositive (OR = 2.06; CI = 1.10-3.83) than those from medium-sized herds/flocks. The present study revealed, for the first time, the widespread occurrence of PPRV antibodies in small ruminants in Djibouti with low prevalence.


Detection and Molecular Characterization of Babesia canis vogeli and Theileria annulata in Free-Ranging Dogs and Ticks from Shahriar County, Tehran Province, Iran.
We aimed to detect and characterize vector-borne parasites of Babesia and Theileria in dog and ticks by PCR assay. Canine babesiosis is a significant tick-borne disease caused by different Babesia species. As the infection has not been reported in Shahriar region Tehran, Iran, molecular techniques allowed us to identify tick-borne parasites in asymptomatic dogs. The number of 40 dog peripheral blood samples and 27 skin attached ticks were analyzed by molecular PCR assay. The specific primers were used for detecting Babesia canis, B. gibsoni and T. annulata. B. c. vogeli was detected in 10 dog blood samples (25%). Additionally, T. annulata infection was identified in 13 dog blood samples (32.5%) and 18 isolated tick DNAs (66.7%). The results of PCR were confirmed by 18S rRNA and Tams1 gene sequence analyzing and have been registered in GenBank under following accession numbers for B. c. vogeli (MH793502) and T. annulata (MK105284). Conclusion: The verification of T. annulata infection in free-ranging dogs and ticks shows dogs might be considered as important natural carriers/reservoirs for T. annulata in enzootic region for bovine theileriosis. The obtained data may be useful for veterinary practitioners and dog owners to aware of Babesia and Theileria infection in dog and tick to establish the effective preventive measures.


Evolution of the coronary care unit: clinical characteristics and temporal trends in healthcare delivery and outcomes.
To describe long-term temporal trends in patient characteristics, processes of care, and in-hospital outcomes among unselected admissions within the contemporary coronary care unit. Hospital administrative database that records both payment and operation data. Coronary care unit of a large, academic, tertiary-care medical institution. A total of 29,275 patients admitted from January 1, 1989 through December 31, 2006. Unadjusted time-trend plots were created for all variables of interest, and multivariable modeling of coronary care unit death was performed. Temporal trends in Coronary Care Unit and in-hospital mortality, length-of-stay, demographic characteristics, discharge diagnoses, Coronary Care Unit procedures, and Charlson comorbidity scores were evaluated. Admission severity increased significantly over time (p < .001), but hospital length-of-stay decreased (p < .001). The proportion of coronary care unit admissions with non-ST-segment elevation myocardial infarction increased (p < .001), whereas ST-segment elevation myocardial infarction decreased (p < .001). The prevalence of non-cardiovascular diagnoses increased, with the rate greatest for comorbid critical illnesses, including sepsis, acute kidney injury, and respiratory failure (all p < .001). The use of non-cardiac procedures, such as mechanical ventilation and central venous catheterization, also increased over time (p < .001). Unadjusted coronary care unit and in-hospital mortality did not change during the study period, although death did decrease in the adjusted setting. Substantial changes have occurred over time in patient characteristics, diagnoses, and procedures within the coronary care unit of a large, academic medical center. In particular, there have been significant increases in noncardiovascular critical illness, the results of which may be influencing patient outcomes. These findings underscore an existing need to clarify the role of the coronary care unit in contemporary cardiovascular care and to develop strategies for optimal training, staffing, and clinical investigation.


Effects of Doping Ni on the Microstructures and Thermoelectric Properties of Co-Excessive NbCoSn Half-Heusler Compounds.
The half-Heusler (HH) compound NbCoSn with 18 valence electrons is a promising thermoelectric (TE) material due to its appropriate electrical properties as well as its suitable thermal and chemical stability. Nowadays, doping/substitution and tailoring of microstructures are common experimental approaches to enhance the TE performance of HH compounds. However, detailed theoretical insights into the effects of doping on the microstructures and TE properties are still missing. In this work, the microstructure of NbCoSn was tailored through precipitating the full-Heusler phases in the matrix by changing the nominal ratio of Co and Ni on the Co sites, focusing on the resulting TE properties. Further, first-principles calculations were employed to understand the relationship between the microstructure and the TE properties from the thermodynamic point of view. Detailed analysis of the electronic structure reveals that the presence of excess Co/Ni contributes to the increasing carrier concentration. Through an increase in the electrical conductivity and a reduction in the thermal conductivity, the TE performance is improved. Therefore, the present work offers a new pathway and insights to enhance the TE properties by modifying the microstructure of HH compounds via tailoring the chemical compositions.


The effectiveness of teaching a relaxation technique to patients undergoing elective cardiac catheterization.
The effects of a relaxation technique (RT) on anxiety, vital signs, procedure length, and amount of diazepam given were examined in patients undergoing cardiac catheterization (CC). Forty patients were randomly assigned to an experimental (RT) or a control (no RT) group. No significant differences were found between groups in pre-CC or post-CC State-Trait Anxiety Inventory (STAI) scores, vital signs, or procedure length. The experimental group received significantly less diazepam, and their STAI scores declined significantly.


Self-Collected Saline Gargle Samples as an Alternative to Health Care Worker-Collected Nasopharyngeal Swabs for COVID-19 Diagnosis in Outpatients.
We assessed the performance, stability, and user acceptability of swab-independent self-collected saliva and saline mouth rinse/gargle sample types for the molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults and school-aged children. Outpatients who had recently been diagnosed with COVID-19 or were presenting with suspected COVID-19 were asked to have a nasopharyngeal (NP) swab collected and provide at least one self-collected sample type. Participants were also asked about sample acceptability using a five-point Likert scale. For those previously diagnosed with COVID-19, all samples underwent real-time PCR testing using a lab-developed assay, and the majority were also tested using an FDA-authorized assay. For those presenting with suspected COVID-19, only those with a positive nasopharyngeal swab sample went on to have other samples tested. Saline mouth rinse/gargle and saliva samples were tested daily at time zero, day 1, and day 2 to assess nucleic acid stability at room temperature. Fifty participants (aged 4 to 71 years) were included; of these, 40 had at least one positive sample and were included in the primary sample yield analysis. Saline mouth rinse/gargle samples had a sensitivity of 98% (39/40), while saliva samples had a sensitivity of 79% (26/33). Both saline mouth rinse/gargle and saliva samples showed stable viral RNA detection after 2 days of room temperature storage. Mouth rinse/gargle samples had the highest (mean, 4.9) and health care worker (HCW)-collected NP swabs had the lowest acceptability scores (mean, 3.1). In conclusion, saline mouth rinse/gargle samples demonstrated higher combined user acceptability ratings and analytical performance than saliva and HCW-collected NP swabs. This sample type is a promising swab-independent option, particularly for outpatient self-collection in adults and school-aged children.


Intra-articular injection versus portal infiltration of 0.5% bupivacaine following arthroscopy of the knee: a prospective, randomised double-blinded trial.
The administration of intra-articular local anaesthetic is common following arthroscopy of the knee. However, recent evidence has suggested that bupivacaine may be harmful to articular cartilage. This study aimed to establish whether infiltration of bupivacaine around the portals is as effective as intra-articular injection. We randomised 137 patients to receive either 20 ml 0.5% bupivacaine introduced into the joint (group 1) or 20 ml 0.5% bupivacaine infiltrated only around the portals (group 2) following arthroscopy. A visual analogue scale was administered one hour post-operatively to assess pain relief. Both patients and observers were blinded to the treatment group. A power calculation was performed. The mean visual analogue score was 3.24 (sd 2.20) in group I and 3.04 (sd 2.31) in group 2. This difference was not statistically significant (p = 0.62). Infiltration of bupivacaine around the portals had an equivalent effect on pain scores at one hour, and we would therefore recommend this technique to avoid the possible chondrotoxic effect of intra-articular bupivacaine.


Evaluation of MGIT 960 and the colorimetric-based method for tuberculosis drug susceptibility testing.
Dr Cetrángolo Hospital, Buenos Aires Province, Argentina. Evaluation of the BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 system and the colorimetric-based method (CMM) for first- and second-line drug susceptibility testing (FL-DST, SL-DST) against Mycobacterium tuberculosis. FL-DST was studied using SIRE MGIT 960. Minimal inhibitory concentrations (MICs) for isoniazid (INH), streptomycin, rifampicin (RMP), ethambutol (EMB) and levofloxacin (LVX) were also determined by CMM using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT). MICs for amikacin (AMK), kanamycin (KM), capreomycin (CPM), ethionamide (ETH), cycloserine, ofloxacin (OFX), linezolide (LZ) and moxifloxacin (MFX) were determined on 94 multidrug-resistant M. tuberculosis isolates by MGIT 960 and CMM. Statistical methods were applied to define drug-susceptible and drug-resistant isolates on the basis of the comparison between results obtained by gold standards. A total of 1626 clinical isolates were studied. Critical drug concentrations could be defined in less than 10 days for both CMM and MGIT 960. CMM was cheaper but more laborious than MGIT 960. The highest performances of both methods were achieved for AMK, RMP, OFX, LZ and MFX, followed by INH, ETH, KM, CPM and LVX (tested only by CMM). Both methods could be implemented as rapid diagnostic tools to detect drug-resistant isolates in clinical practice.


Dedifferentiated classic adamantinoma of the tibia: a report of a case with eventual complete revertant mesenchymal phenotype.
Adamantinomas of the long bones are low-grade malignant tumours. They seem to be related to osteofibrous dysplasia with a mesenchymal-to-epithelial transformation. We report a case of an adamantinoma with a revertant sarcomatoid transformation that showed a complete loss of epithelial differentiation. It corresponded to a 41-year-old male presented with an 8-cm multilobated lesion in the centre of the distal tibia. On the en bloc resection specimen, areas of classic adamantinoma were found but most of the tumor corresponded to a high-grade neoplasm with 2 histologic patterns: one made up by epithelial nests with a basaloid arrangement and positive for pankeratins and so-called glandular keratins, and a second sarcomatoid component, negative for these epithelial markers. Five months after surgery the patient had a massive relapse that consisted solely of the second sarcomatous component also negative for epithelial antibodies.Three cases of adamantinomas with sarcomatoid transformation of the epithelial component have been described but the tumours still preserved an epithelial immunophenotype. However, our case represents the extreme end of the sarcomatoid dedifferentiation of a classic adamantinoma with complete sarcomatoid transformation and total loss of epithelial markers. To our knowledge this has not been described previously.


Patellar tilt and subluxation in total knee arthroplasty. Relationship to pain, fixation, and design.
Two hundred thirty-four primary total knee prostheses were evaluated with a 45 degrees merchant view to examine patellar position and fixation. Despite a standardized technique for obtaining roentgenographs, patellar position varied with leg position. Overall, 54.7% tracked centrally, 31.2% tilted, and 14.5% displaced. The incidence of these findings was the same whether the patella was domed or congruent. Neither pain scores nor fixation were affected by position. Postoperative tilt and displacement were more common in patellae that were tilted preoperatively. The incidence of postoperative tilt or displacement was not significantly different in knees in which a lateral release was performed. Patellar tilt in some patients seems inevitable despite careful technique because intraoperative tests are static and postoperative function is dynamic. This does not bode well for wear in a metal-backed patella. Tilt caused increased loading at the periphery of the component where most metal-backed prostheses have thin polyethylene.


Sexual system, sex ratio, and group living in the shrimp Thor amboinensis (De Man): relevance to resource-monopolization and sex-allocation theories.
The sexual system of the symbiotic shrimp Thor amboinensis is described, along with observations on sex ratio and host-use pattern of different populations. We used a comprehensive approach to elucidate the previously unknown sexual system of this shrimp. Dissections, scanning electron microscopy, size-frequency distribution analysis, and laboratory observations demonstrated that T. amboinensis is a protandric hermaphrodite: shrimp first mature as males and change into females later in life. Thor amboinensis inhabited the large and structurally heterogeneous sea anemone Stichodactyla helianthus in large groups (up to 11 individuals) more frequently than expected by chance alone. Groups exhibited no particularly complex social structure and showed male-biased sex ratios more frequently than expected by chance alone. The adult sex ratio was male-biased in the four separate populations studied, one of them being thousands of kilometers apart from the others. This study supports predictions central to theories of resource monopolization and sex allocation. Dissections demonstrated that unusually large males were parasitized by an undescribed species of isopod (family Entoniscidae). Infestation rates were similarly low in both sexes (≈11%-12%). The available information suggests that T. amboinensis uses pure search promiscuity as a mating system. This hypothesis needs to be formally tested with mating behavior observations and field measurements on the movement pattern of both sexes of the species. Further detailed studies on the lifestyle and sexual system of all the species within this genus and the development of a molecular phylogeny are necessary to elucidate the evolutionary history of gender expression in the genus Thor.


Medication errors recovered by emergency department pharmacists.
We assess the impact of emergency department (ED) pharmacists on reducing potentially harmful medication errors. We conducted this observational study in 4 academic EDs. Trained pharmacy residents observed a convenience sample of ED pharmacists' activities. The primary outcome was medication errors recovered by pharmacists, including errors intercepted before reaching the patient (near miss or potential adverse drug event), caught after reaching the patient but before causing harm (mitigated adverse drug event), or caught after some harm but before further or worsening harm (ameliorated adverse drug event). Pairs of physician and pharmacist reviewers confirmed recovered medication errors and assessed their potential for harm. Observers were unblinded and clinical outcomes were not evaluated. We conducted 226 observation sessions spanning 787 hours and observed pharmacists reviewing 17,320 medications ordered or administered to 6,471 patients. We identified 504 recovered medication errors, or 7.8 per 100 patients and 2.9 per 100 medications. Most of the recovered medication errors were intercepted potential adverse drug events (90.3%), with fewer mitigated adverse drug events (3.9%) and ameliorated adverse drug events (0.2%). The potential severities of the recovered errors were most often serious (47.8%) or significant (36.2%). The most common medication classes associated with recovered medication errors were antimicrobial agents (32.1%), central nervous system agents (16.2%), and anticoagulant and thrombolytic agents (14.1%). The most common error types were dosing errors, drug omission, and wrong frequency errors. ED pharmacists can identify and prevent potentially harmful medication errors. Controlled trials are necessary to determine the net costs and benefits of ED pharmacist staffing on safety, quality, and costs, especially important considerations for smaller EDs and pharmacy departments.


Labeling the endoplasmic reticulum with DiO-C6(3) for imaging.
The eukaryotic cell has evolved to compartmentalize its functions and transport various metabolites among cellular compartments. Therefore, in cell biology, the study of organization and structure/function relationships are of great importance. The endoplasmic reticulum is a highly convoluted, single membrane that is continuous with the outer nuclear membrane and is believed to form a contiguous closed sac within the cell cytosol. Although a probe specific for the endoplasmic reticulum currently does not exist, the DiO-C(6)(3) probe, a cationic dye, is an effective label because of the distinctive intracellular morphology of the endoplasmic reticulum that distinguishes it from other intracellular organelles. This protocol describes the labeling of the endoplasmic reticulum with DiO-C(6)(3).


Laxative abuse among women with eating disorders: an indication of psychopathology?
The results of the scant research on laxative abuse among women with eating disorders suggest that laxative abuse is a diagnostic indicator of greater psychopathology. We further investigated the relationship of history of laxative abuse to eating and related attitudes, impulsivity, and personality pathology. Women assessed in an outpatient clinical setting and diagnosed with anorexia nervosa, binge-eating/purging type (n = 51) or bulimia nervosa, purging type (n = 280) completed measures of laxative abuse, eating and related attitudes, and personality psychopathology at intake. More than one-half of both groups had abused laxatives at some point. History of laxative abuse was unrelated to eating disorder diagnostic category, current age or body weight, history of stealing, self-induced injury, having attempted suicide, interpersonal distrust, maturity fears, or compulsive or dependent personality features. Compared to nonabusers, laxative abusers demonstrated more perfectionism and avoidant personality features. Significant statistical interactions among variables revealed that bulimia nervosa patients who had abused laxatives exhibited the most pathological scores on scales measuring drive for thinness, body dissatisfaction, ineffectiveness, lack of interoceptive awareness, and passive-aggressive and borderline personality features. Anorexia nervosa patients who had abused laxatives had the highest scores on the histrionic scale. Results are discussed with regard to past research and clinical implications. We propose that laxative abuse among eating disordered women may serve different functions depending on diagnosis and underlying personality dynamics.


Collagen production in fat-storing cells after carbon tetrachloride intoxication in the rat. Immunoelectron microscopic observation of type I, type III collagens, and prolyl hydroxylase.
Monospecific antibodies directed against type I, type III collagens, and prolyl hydroxylase were used to clarify the process of liver fibrosis after CCl4 intoxication in rats by the direct immunoperoxidase method. In acute CCl4 intoxication, fat-storing cells (FSCs) were increased in number in the areas of necrosis around the central veins. These FSCs exhibited intense positive stainings for type I, type III collagens, and prolyl hydroxylase in well-developed rough endoplasmic reticula and Golgi apparatus. This was the direct evidence that the collagens formed after CCl4 intoxication are produced by FSCs. In chronic CCl4 intoxication, increased FSCs in and around the fibers also contained strong immunoreactive materials of both collagens and prolyl hydroxylase mainly in the rough endoplasmic reticula. These collagens were also present in the Golgi apparatus and vesicles close to the cytoplasmic membrane, demonstrating the exocytic process of collagen formation of FSCs. In contrast, faint immunoreactions of both collagens were found in the rough endoplasmic reticula and Golgi apparatus of hepatocytes during the process of fibrosis. These findings indicate that FSCs play an important role in fibrogenesis after acute and chronic CCl4 intoxication in the rat.


Microembolization during carotid artery stenting in patients with high-risk, lipid-rich plaque. A randomized trial of proximal versus distal cerebral protection.
The goal of this study was to compare the rate of cerebral microembolization during carotid artery stenting (CAS) with proximal versus distal cerebral protection in patients with high-risk, lipid-rich plaque. Cerebral protection with filters partially reduces the cerebral embolization rate during CAS. Proximal protection has been introduced to further decrease embolization risk. Fifty-three consecutive patients with carotid artery stenosis and lipid-rich plaque were randomized to undergo CAS with proximal protection (MO.MA system, n = 26) or distal protection with a filter (FilterWire EZ, n = 27). Microembolic signals (MES) were assessed by using transcranial Doppler during: 1) lesion wiring; 2) pre-dilation; 3) stent crossing; 4) stent deployment; 5) stent dilation; and 6) device retrieval/deflation. Diffusion-weighted magnetic resonance imaging was conducted before CAS, after 48 h, and after 30 days. Patients in the MO.MA group had higher percentage diameter stenosis (89 ± 6% vs. 86 ± 5%, p = 0.027) and rate of ulcerated plaque (35% vs. 7.4%; p = 0.019). Compared with use of the FilterWire EZ, MO.MA significantly reduced mean MES counts (p < 0.0001) during lesion crossing (mean 18 [interquartile range (IQR): 11 to 30] vs. 2 [IQR: 0 to 4]), stent crossing (23 [IQR: 11 to 34] vs. 0 [IQR: 0 to 1]), stent deployment (30 [IQR: 9 to 35] vs. 0 [IQR: 0 to 1]), stent dilation (16 [IQR: 8 to 30] vs. 0 [IQR: 0 to 1]), and total MES (93 [IQR: 59 to 136] vs. 16 [IQR: 7 to 36]). The number of patients with MES was higher with the FilterWire EZ versus MO.MA in phases 3 to 5 (100% vs. 27%; p < 0.0001). By multivariate analysis, the type of brain protection was the only independent predictor of total MES number. No significant difference was found in the number of patients with new post-CAS embolic lesion in the MO.MA group (2 of 14, 14%) as compared with the FilterWire EZ group (9 of 21, 42.8%). In patients with high-risk, lipid-rich plaque undergoing CAS, MO.MA led to significantly lower microembolization as assessed by using MES counts.


Sport injuries: a review of outcomes.
Injuries can counter the beneficial aspects related to sports activities if an athlete is unable to continue to participate because of residual effects of injury. We provide an updated synthesis of existing clinical evidence of long-term follow-up outcome of sports injuries. A systematic computerized literature search was conducted on following databases were accessed: PubMed, Medline, Cochrane, CINAHL and Embase databases. At a young age, injury to the physis can result in limb deformities and leg-length discrepancy. Weight-bearing joints including the hip, knee and ankle are at risk of developing osteoarthritis (OA) in former athletes, after injury or in the presence of malalignment, especially in association with high impact sport. Knee injury is a risk factor for OA. Ankle ligament injuries in athletes result in incomplete recovery (up to 40% at 6 months), and OA in the long term (latency period more than 25 years). Spine pathologies are associated more commonly with certain sports (e.g. wrestling, heavy-weight lifting, gymnastics, tennis, soccer). Evolution in arthroscopy allows more accurate assessment of hip, ankle, shoulder, elbow and wrist intra-articular post-traumatic pathologies, and possibly more successful management. Few well-conducted studies are available to establish the long-term follow-up of former athletes. To assess whether benefits from sports participation outweigh the risks, future research should involve questionnaires regarding the health-related quality of life in former athletes, to be compared with the general population.


Nutrition and diet for healthy lifestyles in Europe: the 'Eurodiet' Project.
The aims of this project are to formulate a strategy and action plan for developing and implementing European dietary guidelines. The project is supported by DGV/F/3 and was initiated in October 1998. The work plan has entailed the formation of Working Parties composed of prominent experts from the member states to prepare consensus documents on the state of the art in Europe and the added value of European population-based guidelines. These groups are addressing 4 inter-linked components of the project: (1) evaluation of the role of diet and lifestyles in health & disease patterns in Europe; (2) the feasibility of developing an EU-wide framework for food-based dietary guidelines; (3) public health nutrition strategies for implementing FBDGs and for enhancing physically active lifestyles in Europe and (4) an evaluation of policy, trade, economic and technological aspects to improving nutritional status and lifestyles in the EU. Stakeholders from the spectrum of interests involved are invited to assess and debate the science and policy implications of these documents, which will be presented at a European Conference in May 2000. Recommendations in the form of a practical, evidence based policy document will be presented to the European Commission, the Council of Ministers and the European Parliament.


The efficacy of parent training for promoting positive parent-toddler relationships.
The effectiveness of a parent training program for promoting positive parent-child relationships was examined among families of 2-year-olds. Forty-six mothers and fathers and their toddlers were assigned to either an intervention or comparison group. Intervention group parents participated in a 10-week program that focused on principles for effectively interacting with their toddlers. Parents completed measures of parenting self-efficacy, depression, stress, and perceptions of their toddler's behaviors and were videotaped playing with their toddlers preintervention, postintervention, and 3 months following the intervention. Repeated measures ANOVAs showed that the parent training program led to significant increases in maternal self-efficacy, decreases in maternal stress, and improvements in the quality of mother-toddler interactions. No significant effects were found among fathers. Explanations for obtaining different outcomes for mothers and fathers are discussed and directions for future research are recommended.


Factors that may explain interstate differences in certificate-of-need decisions.
A major difficulty in conducting studies of the impact of certificate-of-need programs is in accounting for interstate differences in program characteristics. This paper addresses this problem by examining the empirical relationship between various characteristics of certificate-of-need programs and program decisions, measured in terms of the approvals of hospital capital projects. Aggregate data on capital expenditure approvals and net bed change approvals for 28 States are correlated with an index of each State's regulatory characteristics that was developed in an earlier study. In addition, a multivariate model of certificate-of-need approvals is estimated in which certain measures associated with the need for hospital capital in a State are introduced, along with the indices of regulatory characteristics, to explain interstate differences in regulatory characteristics, to explain interstate differences in program decisions. The results of this analysis indicate that although regulatory characteristics are significantly correlated with the relative number of new beds approved, they have little correlation with total capital expenditure approvals. Moreover, variables reflecting the need for new hospital capital in a State, such as past population growth and existing hospital capacity, appear to be more important than regulatory characteristics in explaining the relative amount of capital approvals.


Regulation of pea mitochondrial pyruvate dehydrogenase complex : does photorespiratory ammonium influence mitochondrial carbon metabolism?
Inactivation of the pyruvate dehydrogenase complex catalyzed by pyruvate dehydrogenase kinase was studied using intact mitochondria purified from green leaf tissue of pea (Pisum sativum L.) and dialyzed mitochondrial extracts. Thiamine pyrophosphate was inhibitory in dialyzed extracts but not in intact mitochondria, except in the presence of high concentrations of Na(+). NH(4) (+), at concentrations as low as 20 micromolar, markedly stimulated inactivation in dialyzed extracts. K(+) in the range 1 to 10 millimolar also enhanced inactivation. In contrast, Na(+) was without affect at lower concentrations but was inhibitory at 10 to 100 millimolar levels. The effect of NH(4) (+) is discussed in relation to a possible regulatory interaction between photorespiratory NH(4) (+) production and the entry of carbon into the tricarboxylic acid cycle by way of the pyruvate dehydrogenase complex.


Co-circulation of Plasmodium and Bacterial DNAs in Blood of Febrile and Afebrile Children from Urban and Rural Areas in Gabon.
Malaria is considered to be the most common etiology of fever in sub-Saharan Africa while bacteremias exist but are under assessed. This study aimed to assess bacteremias and malaria in children from urban and rural areas in Gabon. DNA extracts from blood samples of 410 febrile and 60 afebrile children were analyzed using quantitative polymerase chain reaction. Plasmodium spp. was the microorganism most frequently detected in febrile (78.8%, 323/410) and afebrile (13.3%, 8/60) children, (P < 0.001). DNA from one or several bacteria were detected in 15 febrile patients (3.7%) but not in the controls (P = 0.1). This DNA was more frequently detected as co-infections among febrile children tested positive for Plasmodium (4.6%, 15/323) than in those tested negative for Plasmodium (0%, 0/87; P = 0.04). The bacteria detected were Streptococcus pneumoniae 2.4% (10/410), Staphylococcus aureus 1.7% (7/410), Salmonella spp. 0.7% (3/410), Streptococcus pyogenes 0.2% (1/410) and Tropheryma whipplei 0.2% (1/410) only in febrile children. Coxiella burnetii, Borrelia spp., Bartonella spp., Leptospira spp., and Mycobacterium tuberculosis were not observed. This paper reports the first detection of bacteremia related to T. whipplei in Gabon and shows that malaria decreases in urban areas but not in rural areas. Co-infections in febrile patients are common, highlighting the need to improve fever management strategies in Gabon.


Use of autogenous bone graft compared with RhBMP in high-risk patients: a comparison of fusion rates and time to fusion.
A retrospective study. To evaluate whether recombinant human bone morphogenetic protein (rhBMP-2) can improve fusion rates and time to fusion in high-risk patients when compared with autograft in lumbar posterolateral fusion. The use of rhBMP-2 in the general population for posterolateral fusion has resulted in relatively good reported outcomes; however, it is currently considered "off-label" use. Few studies, however, have determined the outcomes of rhBMP-2 when used in patients with numerous risk factors for a pseudarthrosis. One hundred ninety-five patients were divided into 4 groups depending on fusion material and the presence/absence of fusion-related risk factors for nonunions; group A was defined as rhBMP-2 used in the presence of high-risk factors (FRRF), group B was defined as rhBMP-2 used in the absence of FRRF, group C was defined as autograft used in the presence of FRRF, and group D was defined as autograft used in the absence of FRRF. The time to fusion, fusion rate were compared between each group. The time to fusion was significantly faster in group B than in group D in patients with no history of smoking (P<0.05), hypertension (P<0.01), or other significant comorbidity (P<0.05). The time to complete fusion was also significantly faster in group B than in group D in patients under the age of 65 (P<0.05), patients undergoing primary surgery (P<0.05), single-level surgery (P<0.01), no smoking history (P<0.05), no diabetes mellitus (P<0.01), no hypertension (P=0.001), no osteoporosis (P<0.01), and no significant comorbidity (P<0.01). Although the fusion rate was higher in group B than in group D, with the exception of sex and single-level surgery, there were no significant differences between groups B and D. Although initial fusion mass and time to solid fusion was faster in group A than in group C, there were no significant differences between groups A and C. In addition, fusion rates were higher in group C than in group A, looking at all factors except revision surgery, but the differences were not statistically significant. With relative low dosage of rhBMP-2 compared with the dose used in Food and Drug Administration trial, in patients without fusion-related risk factors, rhBMP-2 may lead to acceptable fusion rates and faster fusion time when compared with autograft. Therefore, rhBMP-2 may serve as an acceptable alternative to autogenous bone graft in patients without fusion-related risk factors undergoing instrumented posterolateral lumbar fusions. When compared with patients with fusion-related risk factors, the use of rhBMP-2 was comparable with autograft but was not sufficient to overcome all aspects of the weakened osteoinductive capacity encountered in patients with these risk factors.


In vitro and in vivo pharmacodynamic properties of the fluoroquinolone ibafloxacin.
The pharmacodynamic properties of a new veterinary fluoroquinolone antimicrobial agent, ibafloxacin, were evaluated. Minimal inhibitory concentrations (MIC), time-kill kinetics, postantibiotic effect (PAE) and postantibiotic subminimal inhibitory concentration effects (PA-SME) were determined against pathogenic canine Gram-negative and Gram-positive bacterial isolates from dermal, respiratory and urinary tract infections. The synergistic interactions between ibafloxacin and its main metabolite, 8-hydroxy-ibafloxacin were investigated. Finally, the efficacy of ibafloxacin was tested in in vivo canine infection models. Ibafloxacin had good activity against Pasteurella spp., Escherichia coli, Klebsiella spp., Proteus spp. and Staphylococcus spp. (MIC90=0.5 microg/mL), moderate activity against Bordetella bronchiseptica, Enterobacter spp. and Enterococcus spp. (MIC50=4 microg/mL) and low activity against Pseudomonas spp. and Streptococcus spp. The time-killing analysis confirmed that ibafloxacin was bactericidal with a broad spectrum of activity. The PAE and PA-SME were between 0.7-2.13 and 1-11.5 h, respectively. Finally, studies in dog models of wound infection and cystitis confirmed the efficacy of once daily oral ibafloxacin at a dosage of 15 mg/kg. Additional studies are needed to better define the importance of AUC/MIC (AUIC) and Cmax/MIC ratios on the outcome of fluoroquinolone therapy in dogs.


Synthesis and structural, electrochemical and photophysical studies of triferrocenyl-substituted 1,3,5-triphenylbenzene: a cyan-light emitting molecule showing aggregation-induced enhanced emission.
Triferrocenyl-substituted 1,3,5-triphenylbenzene was successfully synthesized in high yield. Single-crystal X-ray diffraction experiments revealed that the internal rotations of the ferrocenyl moieties are significantly restricted in the solid phase and that there are no significant π stacking interactions therein. The photoluminescence of the crystals is essentially the same as that of dilute chloroform solutions. However, studies of this cyan-light emitting substance in mixtures of chloroform and methanol revealed the aggregation-induced enhanced emission (AIEE) feature that boosts its fluorescence quantum yield from 13% up to 74%. We demonstrate the AIEE effect for a new class of easy-to-prepare aromatic molecules containing several metallocene units for the first time.


Can 'Hebb' Be Distracted? Testing the Susceptibility of Sequence Learning to Auditory Distraction.
Sequence learning plays a key role in many daily activities such as language and skills acquisition. The present study sought to assess the nature of the Hebb repetition effect-the enhanced serial recall for a repeated sequence of items compared to random sequences-by examining the vulnerability of this classical sequence-learning phenomenon to auditory distraction. Sound can cause unwanted distraction by either interfering specifically with the processes involved in the focal task (interference-by-process), or by diverting attention away from a focal task (attentional capture). Participants were asked to perform visual serial recall, in which one to-be-remembered sequence was repeated every four trials, while ignoring irrelevant sound. Whereas both changing-state (Experiment 1) and deviant sounds (Experiment 2) disrupted recall performance compared to steady-state sounds, performance for the repeated sequence increased across repetitions at the same rate regardless of the sound condition. Such findings suggest that Hebbian sequence learning is impervious to environmental interference, which provides further evidence that the Hebb repetition effect is an analogue of word-form learning.


Calculation Model of Regional Economic Growth Efficiency by Intelligently Optimized Interunit Layout.
With the development of the economy, especially since the reform and opening up, the actual conditions that China's economic development faces have also changed, and the development goals have also been adjusted accordingly. However, since the reform and opening up, China's economy has still largely relied on the extended reproduction of the extension type. It basically develops along a high-input, low-efficiency path. The effectiveness of regional economic development has always been one of the most important debates in economics, and it has attracted great attention in different countries and regions around the world. So far, people have conducted a lot of theoretical and practical research on the effectiveness of regional development and put forward many practical countermeasures. However, it has achieved little in practice, and the original form of high growth and low efficiency has not been effectively reversed. In this paper, economic development is divided into two parts. The first part consists of the impact of changes in the quantity of factors of production on economic growth and the impact of the efficiency of economic growth on the entire economy. The second part consists of the annual average efficiency of economic growth. The average annual contribution of various production factors to economic growth and the economic growth efficiency of changes in the allocation of capital industries were 6.21%, 5.02%, 4.05%, 3.9%, and 3.3%, respectively in the past five years.


[The human genome--chromosome 20].
There is an increasing interest on one of the smallest human chromosomes as it is shown by the First International Symposium on the Human Chromosome 20 and by the genetic map prepared by EUROGEN. The conserved part of the long arm of human chromosome 20 is synthenic with the distal part of the mouse chromosome 2 allowing for some analogies between them. Human chromosome 20 contains several important genes for the human pathology. Mutations of one of them, the vasopressin-neurophysin II gene, are responsible for hereditary neurohypophyseal diabetes insipidus. Severe combined immunodeficiency due to adenosin deaminase deficiency is the first human disorder successfully treated by somatic gene therapy. Spongiform encephalopathies are related to mutation and/or polymorphisms of the PRNP amyloid gene. One form of benign familiar neonatal convulsions is mapped to a specific locus on chromosome 20. In some families, maturity onset diabetes of the young (MODY) is caused by alterations of a hypothetical gene closely linked to the ADA locus. Allegile syndrome is often associated with deletions and microdeletions of the short arm of the chromosome. Finally, deletions of the long arm of the chromosome is a frequent finding in several hematologic malignities, specifically in myeloproliferative disorders and myelodysplastic syndromes.


Demonstration of prolactin at the ultrastructural level in a pituitary adenoma by the use of colloidal gold labelling.
A prolactin-secreting pituitary adenoma was removed in a 38-year-old man. The tumor was classified as a chromophobe adenoma on the basis of tinctorial staining, but immunocytochemistry revealed that cells reacted with anti-PRL serum. Electron microscopy showed secretory granules and evidence of high metabolic activity (well developed Golgi apparatus and rough endoplasmic reticulum). Immunoelectron microscopy by the immunogold staining method allowed a clear definition of prolactin containing granules.


Obstetrics and perinatal outcome of pregnancies after the age of 45.
We set out to describe the maternal and perinatal outcome of pregnancies in women >/= 45 years old at the time of delivery. A retrospective review of hospital deliveries after 28 weeks of pregnancy was performed at the Princess Badeea Teaching Hospital (PBTH) in North Jordan for patients delivered between 1 April 1994 and 31 December 1997. During the study period, there were 114 women aged >/= 45 years at delivery at the PBTH. The incidence was 3.3 per 1000 births. The median maternal age was 45 years. The majority of women (81.6%) were 45-46 years old. Maternal ages were 45 (n =64), 46 (n =29), 47 (n =9), 48 (n =8), 49 (n =2) and 50 (n =2) years. Median gravidity was 10, median parity was seven. Forty-four (38.6%) patients had obstetric complications. The most frequent complication was diabetes mellitus (9.6%), followed by hypertension (4.4%). Caesarean section was performed in 32.5%. There were nine stillbirths and four early neonatal deaths, the perinatal mortality rate was 114/1000 births. We conclude that women >/= 45 years old at delivery have high perinatal mortality rate and we also noted a higher incidence of placental abruption, placenta praevia and caesarean delivery, compared with a younger group of women.


Mental health problems in the Gomel region (Belarus): an analysis of risk factors in an area affected by the Chernobyl disaster.
The epidemiology of mental problems in the Gomel region in the republic of Belarus was studied in a two-stage survey of a broad based population sample (N = 1617), using the General Health Questionnaire (12-item version) and the Munich Diagnostic Checklist for DSM-III-R. The Gomel region is one of the areas that was most severely affected by the Chernobyl nuclear disaster in 1986. In the studied population sample 64.8% had a GHQ-score above the threshold of 2. A DSM-III-R psychiatric disorder was present in 35.8%, with especially high rates for affective (16.5%) and anxiety disorders (12.6%). Dysthymia, general anxiety disorder, adjustment disorders and 'not otherwise specified syndromes' made up almost two-thirds of the observed morbidity (22.9%). A higher prevalence of mental health problems, both in terms of the GHQ and the DSM-III-R was observed among people who have been evacuated and in mothers with children under 18 years of age. These data indicate that the Chernobyl nuclear disaster may be partly responsible for the high prevalence of (milder) psychiatric disorders and psychological distress in the Gomel region, even 6 years after the event. Future studies comparing the data from Gomel region with an unexposed area will have to provide a more definite answer concerning the impact of this nuclear disaster on mental health.


Mechanical analysis of femoral neck fracture fixation with dynamic condylar screw in synthetic bone.
To analyze statistically results in biomechanical testing of fixation of femoral neck Pauwels type III fractures, on synthetic bone, with dynamic condylar screw (DCS) and control group. Ten synthetic bones of a national brand were used. Test Group: fixation was performed after osteotomy at 70(o) tilt using DCS plate with four holes. We analyzed the resistance of this fixation with 5 mm displacement and rotational deviation (Step 1) and with10 mm (Step 2). the models were tested in their integrity until the femoral neck fracture occurred. The values of the test group in Step 1 showed a mean of 974N and SD = 114N. In Stage 2, we obtained on average 1335N and SD = 98N. The values in the control group were: 1544N, 1110N, 1359N, 1194N, 1437N, respectively. Statistical analysis using the Mann-Whitney test for comparison of the maximum force (N) between the test group and the control, in Step 2, demonstrated that there is no significant difference between the DCS and control plates (p = 0.91). There is no significant difference between the DCS boards and the control group exposed to full resistance. Level of Evidence III, Case Control.


Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.
The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)


The zebrafish colourless gene regulates development of non-ectomesenchymal neural crest derivatives.
Neural crest forms four major categories of derivatives: pigment cells, peripheral neurons, peripheral glia, and ectomesenchymal cells. Some early neural crest cells generate progeny of several fates. How specific cell fates become specified is still poorly understood. Here we show that zebrafish embryos with mutations in the colourless gene have severe defects in most crest-derived cell types, including pigment cells, neurons and specific glia. In contrast, craniofacial skeleton and medial fin mesenchyme are normal. These observations suggest that colourless has a key role in development of non-ectomesenchymal neural crest fates, but not in development of ectomesenchymal fates. Thus, the cls mutant phenotype reveals a segregation of ectomesenchymal and non-ectomesenchymal fates during zebrafish neural crest development. The combination of pigmentation and enteric nervous system defects makes colourless mutations a model for two human neurocristopathies, Waardenburg-Shah syndrome and Hirschsprung's disease.


Effect of chronic administration of antidepressants on duration of immobility in rats forced to swim.
Chronic administration of imipramine and desipramine significantly reduced the duration of immobility in rats forced to swim in comparison with acute administration. However, amitriptyline did not potentiate the reductive effect of chronic administration. Chlorimipramine, a selective serotonin uptake inhibitor, did not affect the duration of immobility in both the acute and chronic administration. On the other hand, the chronic administration of chlorpromazine, haloperidol and diazepam enhanced the duration of immobility, whereas their acute administration had no effect on it. Sulpiride reduced and enhanced the duration of immobility by the acute and chronic administration, respectively. The present results suggest that the chronic administration of drugs to rats in a forced swimming test can clarify the characteristics of the psychotropic drugs.