The IGFR1 inhibitor NVP-AEW541 disrupts a pro-survival and pro-angiogenic IGF-STAT3-HIF1 pathway in human glioblastoma cells.
Inappropriate activation of the IGF (insulin-like growth factor) system has been implicated in the growth and progression of a number of tumor types. Recent evidence indicates a possible role for the IGF system in modulating/mediating tumor cell response to hypoxia, a common occurrence in solid tumors, and particularly in malignant gliomas, causing tumor cells either to die, or to mount a pleiotropic adaptive response that is mainly orchestrated through activation of the hypoxia-inducible transcription factor HIF1. Experimental evidence suggests possible links between IGF- and HIF1-dependent signaling pathways, as well as a role for activated STAT3 in mediating their activities. Interestingly, igf2 is among the target genes transactivated by HIF1, thereby providing the missing link in a hypothetical autocrine self-amplifying circuit. The present study investigates the presence of the IGF-HIF1-VEGF axis in the human glioma cell line U-87 MG, and characterizes its molecular effectors. Our results show that exogenous IGF-I causes IGF1R and STAT3 activation, and increases HIF1alpha protein levels and HIF1 trascriptional activity, inducing VEGF release; a similar response, mediated by IGF-II release, is observed following HIF1alpha stabilization. The existence of an autocrine loop is confirmed by its down-regulation following inactivation of IGF1R (using the IGF1R-specific tyrosine kinase inhibitor NVP-AEW541), STAT3 (transfecting the cells with an expression vector encoding a dominant negative form of STAT3), or HIF1 (using the small molecule inhibitor YC-1). The ability of NVP-AEW541 to block this circuit could be beneficial in suppressing the growth and angiogenic potential of hypoxic glial tumors.


Matching Kidneys and Urines: Establishing Noninvasive Surrogates of Intrarenal Events in Primary Glomerulonephritis.
Kidney biopsy is the gold standard procedure for providing diagnostic and prognostic information for patients with glomerular-based diseases, however, the utility of this procedure for assessing longitudinal disease activity is limited. The intense search for noninvasive biomarkers of kidney disease activity and injury is driven in large part by the inherent risks of the kidney biopsy procedure and limited information derived from the morphologic description of biopsy findings. Furthermore, gaps in our understanding of the core intrarenal molecular processes underlying the development and progression of glomerular-based diseases has limited the development of effective targeted therapy. In this review, we discuss the potential utility of molecular analysis of the urine to provide a dynamic window into intrarenal molecular and morphologic responses. We focus on molecular analysis of the urine to identify noninvasive surrogate markers of kidney responses, with the goal of using these biomarkers as more sensitive indicators of progression and tissue-level responses to therapeutic interventions in patients with primary glomerulonephritis.


[Protective effect of losartan on endothelial cells exposed to high glucose levels in vitro].
To investigate the effect of losartan (an angiotensin II type I receptor antagonist) on endothelial cells exposed to high glucose in vitro and related mechanism. Vascular endothelial cells of human umbilical vein were cultured in media with high glucose levels. The activities of SOD and CAT, the level of MDA were measured by spectrophotometry in the conditioned media of endothelial cells, the VEGF mRNA expression was performed using semi-quantitative reverse transcription PCR (RT-PCR) in the cell lysates, and the protein expression of VEGF was examined by enzyme-linked immunosorbent assay (ELISA) in the supernatants of cultured cells. When endothelial cells were cultured in high glucose, the activities of SOD and CAT were significantly decreased, but the level of MDA was markedly increased. However, the high glucose-induced effects were inhibited by losartan. The application of high glucose upregulated the mRNA and protein expression of VEGF in endothelial cells, which was also attenuated by losartan. High glucose disrupts the oxidative equilibrium and increases the expression of VEGF in endothelial cells, which can be inhibited by losartan.


Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma.
Advanced stage neuroblastoma is an aggressive disease with limited treatment options for patients with drug-resistant tumors. Targeted delivery of chemotherapy for pediatric cancers offers promise to improve treatment efficacy and reduce toxicity associated with systemic chemotherapy. The EnGeneIC Dream Vector (EDVTM) is a nanocell, which can package chemotherapeutic drugs and target tumors via attachment of bispecific proteins to the surface of the nanocell. Phase I trials in adults with refractory tumors have shown an acceptable safety profile. Herein we investigated the activity of EGFR-targeted and doxorubicin-loaded EDVTM (EGFREDVTMDox) for the treatment of neuroblastoma. Two independent neuroblastoma cell lines with variable expression of EGFR protein [SK-N-BE(2), high; SH-SY-5Y, low] were used. EGFREDVTMDox induced apoptosis in these cells compared to control, doxorubicin, or non-doxorubicin loaded EGFREDVTM In three-dimensional tumor spheroids, imaging and fluorescence life-time microscopy revealed that EGFREDVTMDox had a marked enhancement of doxorubicin penetration compared to doxorubicin alone, and improved penetration compared to non-EGFR-targeted EDVTMDox, with enhanced spheroid penetration leading to increased apoptosis. In two independent orthotopic human neuroblastoma xenograft models, short-term studies (28 days) of tumor-bearing mice led to a significant decrease in tumor size in EGFREDVTMDox-treated animals compared to control, doxorubicin, or non-EGFR EDVTMDox There was increased TUNEL staining of tumors at day 28 compared to control, doxorubicin, or non-EGFR EDVTMDox Moreover, overall survival was increased in neuroblastoma mice treated with EGFREDVTMDox (P < 0007) compared to control. Drug-loaded bispecific-antibody targeted EDVsTM offer a highly promising approach for the treatment of aggressive pediatric malignancies such as neuroblastoma. Mol Cancer Ther; 17(5); 1012-23. ©2018 AACR.


Binding of estrogen receptor alpha promoter to nuclear proteins of mouse cerebral cortex: effect of age, sex, and gonadal steroids.
Majority of estrogen actions in the brain are mediated by estrogen receptor (ER) alpha which in turn is regulated by several factors like circulating levels of gonadal steroid hormones 17beta-estradiol and testosterone, sex and age of the organism. The expression of ERalpha is regulated through interaction between cis-elements of its promoter and proteins present in the nuclei. Here, we have used electrophoretic mobility shift assay (EMSA) to analyze the effect of age, sex, 17beta-estradiol, and testosterone on the binding of ERalpha promoter (-91 to +46 bp) to nuclear proteins from the mouse cerebral cortex. EMSA revealed the formation of three specific complexes in all groups. However, the intensity of these complexes varied as a function of age, sex and treatment with 17beta-estradiol and testosterone. Nuclear proteins from the cerebral cortex of both sexes showed reduced binding with promoter fragment in old mice. Further, competition analysis indicated stronger binding in females than males of both ages. The extent of binding was reduced by 17beta-estradiol and testosterone treatment in both ages and sexes. Thus, these findings demonstrate differential binding of nuclear proteins to mouse ERalpha promoter which may account for different functions of estrogen in the brain.


Current status of renal transplantation from HCV-positive donors.
Hepatitis C virus (HCV) infection remains frequent among renal transplant (RT) recipients and has a detrimental effect on patient and graft survival. accelerated progression of liver disease due to HCV has been implicated in increased mortality after kidney transplantation but additional outcomes have been related to HCV after RT. all HCV-infected kidney transplant candidates should be considered for liver biopsy before RT. HCV infection should not be considered an absolute contraindication to renal transplantation, although the course of HCV-related liver disease is often progressive. Numerous organ procurement organizations have introduced the policy of accepting kidneys from HCV-positive donors for HCV-positive recipients, but this is still controversial. Single-center experiences have not reported adverse effects on the short-term patient and graft survival, however information from large databases has suggested that RT recipients of HCV-positive donors are independently at risk of mortality even in the modern era of immunosuppression. Renal transplantation should be considered using HCV-seropositive grafts for qualified patients with chronic kidney disease (CKD) stage 5 and HCV infection since good information indicates that the transplantation of kidneys from HCV-infected donors results in improved survival compared to wait-listed and dialysis-dependent candidates. a potential risk related to the use of donor HCV-positive kidneys cannot be excluded, and kidneys from HCV-infected donors should be restricted to recipients with evidence of active viremia at the time of kidney transplantation.


Prognostic importance of delayed Q-wave evolution 3 to 24 hours after initiation of thrombolytic therapy for acute myocardial infarction.
The timing of Q-wave evolution and its prognostic significance was studied in 201 patients who received thrombolytic therapy for a first acute myocardial infarction (AMI). One hundred forty-one patients (70%) had evidence of a Q-wave AMI within 3 hours of the initiation of thrombolytic therapy, 31 (16%) developed Q waves after 3 hours but before hospital discharge, and 29 (14%) were discharged with a non-Q-wave AMI. Laboratory indicators of myocardial damage and in-hospital morbidity and mortality were greater among patients with Q-wave AMIs than with non-Q-wave AMIs. When these indexes were examined with respect to the timing of Q-wave evolution, the prognosis of patients with delayed Q-wave development was similar to that of patients with non-Q-wave AMIs. Thus, compared to patients with early (less than or equal to 3 hours) Q-wave evolution, patients with delayed Q-wave evolution or with a non-Q-wave AMI had a smaller creatine kinase peak (mean 661 to 1,081 vs 1,251 to 1,541 IU; p = 0.005), better preservation of left ventricular function as measured by radionuclide ventriculography before discharge (mean +/- standard deviation 54 +/- 11% vs 47 +/- 13%; p less than 0.01), and a lower incidence of congestive heart failure at discharge (3 vs 15%; p = 0.02). In-hospital mortality was lower among patients with delayed Q-wave evolution or with a non-Q-wave AMI (5 of 141 vs 0 of 60; difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)


Isoform-selective interactions between estrogen receptors and steroid receptor coactivators promoted by estradiol and ErbB-2 signaling in living cells.
Estrogen receptor (ER)alpha and -beta interact with a variety of coactivator proteins, most notably members of the steroid receptor coactivator (SRC) family, and these interactions have been shown to be regulated by estrogenic ligands and growth factor signaling. Here, using fluorescence resonance energy transfer (FRET), the selectivity of different stimulants on ERalpha and -beta interactions with coactivator receptor interaction domains (RIDs) were examined in living cells. We first show that ERalpha and ERbeta homo- and heterodimers form in vivo independently of the presence of 17beta-estradiol (E2) or antiestrogens. We then demonstrate that E2 enhances interactions between ERalpha and the RIDs of SRC-1 and SRC-3, whereas the interaction between ERalpha with the SRC-2 RID is ligand independent. The transcriptionally inactive mutant ERalphaL539A showed no interaction with all three SRC RIDs. Similarly, treatment with the antagonists 4-hydroxytamoxifen and EM-652 abolished all interactions between ERalpha and the SRC RIDs. FRET data also demonstrate that, in contrast to ERalpha, ERbeta interacts with all three SRC RIDs in a ligand-independent manner. However, these interactions were further enhanced or stabilized by E2, whereas the antiestrogen EM-652 abolished all interactions. In the presence of both ERalpha and ERbeta, E2 treatment led to the recruitment of SRC RIDs to the nuclei. Finally, expression of the oncogenic activated ErbB-2/Neu protein specifically enhanced ERalpha but not ERbeta interactions with SRC RIDs to an extent similar to E2-stimulated interactions. In summary, using FRET, we demonstrated preferential interactions between ER isoforms and coactivators upon hormonal treatment and activation of a growth factor signal transduction pathway in living cells.


Silicon based tandem cells: novel photocathodes for hydrogen production.
A photovoltaic tandem cell made of amorphous silicon (a-Si) and microcrystalline silicon (μc-Si) was investigated as a photocathode for hydrogen evolution in a photoelectrochemical device. The electronic and electrochemical properties of the samples were characterized using X-ray photoemission spectroscopy (XPS) and cyclic voltammetry (CV), whereas the morphology of the surface in contact with the electrolyte was investigated by scanning electron microscopy (SEM). The electric efficiency of the tandem cell was determined to be 5.2% in a photoelectrochemical (PEC) setup in acidic solution which is only about half of the photovoltaic efficiency of the tandem cell. A significant improvement in efficiency was achieved with platinum as a catalyst which was deposited by physical vapour deposition (PVD) under ultra-high vacuum (UHV) conditions.


Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 4: Cerebrospinal fluid shunt or endoscopic third ventriculostomy for the treatment of hydrocephalus in children.
The objective of this systematic review was to examine the existing literature comparing CSF shunts and endoscopic third ventriculostomy (ETV) for the treatment of pediatric hydrocephalus and to make evidence-based recommendations regarding the selection of surgical technique for this condition. Both the US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words specifically chosen to identify published articles detailing the use of CSF shunts and ETV for the treatment of pediatric hydrocephalus. Articles meeting specific criteria that had been determined a priori were examined, and data were abstracted and compiled in evidentiary tables. These data were then analyzed by the Pediatric Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to consider treatment recommendations based on the evidence. Of the 122 articles identified using optimized search parameters, 52 were recalled for full-text review. One additional article, originally not retrieved in the search, was also reviewed. Fourteen articles met all study criteria and contained comparative data on CSF shunts and ETV. In total, 6 articles (1 Class II and 5 Class III) were accepted for inclusion in the evidentiary table; 8 articles were excluded for various reasons. The tabulated evidence supported the evaluation of CSF shunts versus ETV. Cerebrospinal fluid shunts and ETV demonstrated equivalent outcomes in the clinical etiologies studied. Both CSF shunts and ETV are options in the treatment of pediatric hydrocephalus. Level II, moderate clinical certainty.


[Infantile hepatic hemangioendothelioma of the liver: report of 11 cases].
We report a restrospective study about 11 patients (9 girls) referred from 1980 through 1994. We undertook this study to determine the efficiency of several methods for diagnosis and treatment. We performed ultrasound, computerized tomography (CT) in each one and magnetic resonance (MR) in 4 cases. Six patients were prescribed steroids, 4 cases were not treated and one patient was operated. A solid lesion with variable ecotexture is noted at ultrasound. CT typically shows a low-attenuation solid lesion with peripheral enhancement. At MR imaging performed with T2-weighted pulse secuences the lesion usually has high signal intensity. We obtained completed remission in 5 cases, one patient was out of control and in the other 5 the sonography showed marked regression in tumor size. We believe CT is an specific method for diagnosis hemangioendothelioma. Sonographic control or steroids must be the initial therapy.


The Four S Model in action for de-escalation. An innovative state hospital-university collaborative endeavor.
In this article, the Four S Model is presented as a working clinical framework for generating structured nursing interventions and treatment plans. The de-escalation process, formalized by the De-escalation/Alternative to Restraint Flowsheet, is one way in which the model is being operationalized to reduce seclusion and restraints. As shown by the flowsheet, the model allows for integration of mental health and mental illness. It spans the scope of nursing practice at all levels, from para-professional to advanced practice nurse, by integrating the mental health concepts of communication, leadership, clinical judgement, critical thinking, and caring within its framework. Most important, the flexibility to individualize treatment that is built into the model allows for generalization to all psychiatric presentations.


Synthesis, Radiosynthesis, and Preliminary in vitro and in vivo Evaluation of the Fluorinated Ceramide Trafficking Inhibitor (HPA-12) for Brain Applications.
Ceramide levels are increased in blood and brain tissue of Alzheimer's disease (AD) patients. Since the ceramide transporter protein (CERT) is the only known protein able to mediate non-vesicular transfer of ceramide between organelle membranes, the modulation of CERT function may impact on ceramide accumulation. The competitive CERT inhibitor N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12) interferes with ceramide trafficking. To understand the role of ceramide/CERT in AD, HPA-12 can be a useful tool to modulate ceramide trafficking. Here we first report the synthesis and in vitro properties of HPA-12 radiolabeled with fluorine-18 and present preliminary in vitro and in vivo positron emission tomography (PET) imaging and biodistribution data. In vitro results demonstrated that the fluorination did not alter the biological properties of HPA-12 since the [fluorine-19]HPA-12, interferes with 5-DMB-ceramide trafficking in HeLa cells. Radiolabeled HPA-12, [fluorine-18]HPA-12, was obtained with a radiochemical yield of 90% and a specific activity of 73 MBq/μmol. PET imaging on wild-type mice showed hepatobiliary clearance and a brain uptake on the order of 0.3 standard uptake value (SUV) one hour post injection. Furthermore, the biodistribution data showed that after removal of the blood by intracardial perfusion, radioactivity was still measurable in the brain demonstrating that the [fluorine-18]HPA-12 crosses the blood brain barrier and is retained in the brain.


[The organization of the preventive work in educational institutions: problems and solutions].
Prevention measures are relevant for children and adolescents as among them there is the high prevalence of leading risk factors for chronic diseases. For the improvement of the preventive work it is necessary the introduction of amendments into the legislative documents and orders of the Ministry of Health, governing health care for children and adolescents in educational organizations. The consistent methodology for primary health care must be provided with the appropriate protocols. It is necessary to perform the systematic work on the reduction of the prevalence of risk factors for children's health and a healthy lifestyle. The number of doctors and nurses in the preschool and educational institutions is insufficient, and in organizations of primary and secondary vocational education is disastrous. Medical personnel departments of medical assistance to students due to the excessive load is not capable to fufill all of their functional responsibilities. Due to the low wages there is a constant reduction of health workers in schools and kindergartens. In the paper there are proposed measures aimed at improving the quality of preventive work in educational organizations.


Acoustooptic beam deflection for spatial frequency multiplexing in high speed holocinematography.
Four holograms are recorded superimposed on the same plate at maximum repetition rates of about 10 kHz. A multiply Q-switched ruby laser produces the series of coherent light pulses for hologram exposure. Image separation of different holograms is achieved by spatial frequency multiplexing. The reference beam direction is altered by a unique acoustooptic beam splitter and deflector unit. The operating principle is a sound pulse-light pulse interception technique. Only one ultrasonic transducer is necessary. The quality of the holograms is demonstrated by the reconstructed images taken of laser produced cavitation bubbles following optical breakdown in water.


Identification of a domain of Escherichia coli primase required for functional interaction with the DnaB helicase at the replication fork.
Primase plays a key role in governing the sequence of events required on the lagging strand during a cycle of Okazaki fragment synthesis. To begin to probe the protein-protein interactions necessary for primase function at the replication fork, we have used limited trypsinolysis to separate primase into two functional domains, an N-terminal domain of 49 kDa (p49) and a carboxyl-terminal domain of 16 kDa (p16). p49 retained primase activity in replication assays that utilized bacteriophage M13 DNA carrying the bacteriophage G4 origin of DNA replication as the template, but was inactive during general priming or the conversion of phi X174 single-stranded circular (ss(c))-DNA to the replicative form (RF) and could not support lagging-strand DNA synthesis at replication forks reconstituted with the phi X-type primosomal proteins and the DNA polymerase III holoenzyme. On the other hand, p16 inhibited those replication reactions that included the replication fork helicase, DnaB (general priming, phi X174 ss(c)-->RF, and at the replication fork), but had no effect on those that did not (M13Gori ss(c)-->RF). These results demonstrate that p49 defines a domain of primase required for catalytic activity, that p16 defines a domain of primase required for functional interaction with DnaB, and that it is a protein-protein interaction with DnaB that attracts primase to the replication fork.


Early feeding of an energy dense diet during acute shigellosis enhances growth in malnourished children.
In a controlled clinical trial, we examined the effect of the short-term feeding of an energy-dense milk cereal formula in malnourished children with clinically severe dysentery due to acute shigellosis. Seventy-five malnourished children, aged 12-48 mo, passing blood or blood with mucous in the stool for < or = 96 h, were offered a hospital diet. In addition, study children (n = 36) were offered a milk-cereal formula with an energy of 5 kJ/g (an 11% protein diet); similarly, control children (n = 39) were offered a milk-cereal formula with an energy content of 2.5 kJ/g (an 11% protein diet). Patients were admitted to the metabolic ward of the Clinical Research and Service Centre, Dhaka, at the International Centre for Diarrhoeal Disease Research, Bangladesh. Patients were studied for 10 hospital days and were then followed up at home after 30 d. After 10 d of dietary intervention, children in the study group had a significantly greater increase vs. controls in weight-for-age (6 vs. 3%, P < 0.001) and in weight-for-height (7 vs. 3%, P < 0.001). Serum prealbumin concentrations were significantly higher (study vs. control) after 5 d (0.214 vs. 0.170 g/L, P = 0.01) and after 10 d (0.244 vs. 0.193 g/L, P = 0.006) of the study. Greater weight-for-age was sustained at home 1 mo after discharge (8 vs. 5%, P = 0.005) from the hospital. Similarly, higher weight-for-height was sustained 1 mo after discharge (8 vs. 5%, P = 0.01). During their stay at home, there was no dietary intervention. The results of this study suggest that short-term feeding of an energy-dense diet enhances growth in malnourished children with acute dysentery due to shigellosis.


Interaction of mucosal immune system and infections in infancy: implications in allergy.
The immune responses to viral antigens and other environmental agents to which the mucosal surfaces of the neonate are exposed during the perinatal period and early infancy are intimately related to the mechanism of innate immunologic reactivity of the mother-and, possibly, to the immunologic elements in the products of lactation for a breast-feeding infant-and the nutritional homeostasis of the neonate. The role of these factors in protecting against pathogenicity of viral infections in the respiratory and intestinal tract, and their impact on the development of allergic disease state in childhood will be reviewed.


Nickel-Catalyzed Cross-Electrophile Coupling of Alkyl Fluorides: Stereospecific Synthesis of Vinylcyclopropanes.
The stereospecific reductive cross-electrophile coupling reaction of 2-vinyl-4-halotetrahydropyrans for vinylcyclopropane synthesis is reported. The nickel-catalyzed reaction occurs with both alkyl fluorides and alkyl chlorides. To the best of our knowledge, this is the first reported cross-electrophile coupling reaction of an alkyl fluoride. Ring contraction proceeds with high stereospecificity, providing selective synthesis of either diastereomer of di- and trisubstituted cyclopropanes. The utility of this methodology is demonstrated by several synthetic applications including the synthesis of the natural product dictyopterene A. 2-Vinyl-4-fluorotetrahydrofurans also undergo stereospecific ring contractions, providing access to synthetically useful hydroxymethyl cyclopropanes.


Dephosphorylation of cofilin accompanies heat shock-induced nuclear accumulation of cofilin.
Cofilin is a widely distributed 21-kDa actin-modulating protein that forms intranuclear actin/cofilin rods in cultured fibroblastic cells exposed to heat shock or 10% dimethyl sulfoxide. In this study, cofilin was shown to be phosphorylated on a serine residue in cultured rat fibroblastic 3Y1 cells. Two-dimensional gel electrophoresis revealed that about 50% of the cofilin was phosphorylated in 3Y1 cells at 37 degrees C. Exposure of the cells to heat shock at 43 degrees C induced dephosphorylation of cofilin. The dephosphorylation of cofilin was detected about 30 min after the temperature shift and was completed within 120 min. Moreover, treatment of cells with 10% dimethyl sulfoxide also caused the dephosphorylation of cofilin. However, incubation of the cells with an isotonic NaCl solution, which induced cytoplasmic actin/cofilin rods, did not induce dephosphorylation of cofilin. Other cellular stress agents such as 6% ethanol or 50 microM sodium arsenite, which caused some heat shock responses in cells, did not induce dephosphorylation of cofilin. Thus, cofilin dephosphorylation was closely correlated with its nuclear accumulation. Incubation of the enucleated 3Y1 cells at 43 degrees C still induced dephosphorylation of cofilin, suggesting that the dephosphorylation occurred mostly in the cytoplasm in intact cells. It is likely that cofilin is dephosphorylated in the cytoplasm prior to its nuclear accumulation.


[Validation of the German version of the Oxford Elbow Score : A cross-sectional study].
Elbow complaints are complex problems leading to severe consequences for affected people and the healthcare system. The German version of the Oxford Elbow Score (OES) is the first German-speaking instrument that specifically measures elbow complaints from the patient's perspective and changes of their health status. The aim of this study is the validation of the German version of the OES. In this context the internal consistency and the construct validity were investigated. 59 patients with elbow complaints completed the German version of the OES, the DASH and the SF-36 in a cross-sectional study. The internal consistency was calculated with Cronbach's alpha coefficients. Spearman's correlation coefficients were used to confirm construct validity. Cronbach's alpha for pain, function and psychological subscales was 0.88, 0.81 and 0.90, respectively. The whole questionnaire presents a Cronbach's alpha value of 0.93. Convergent construct validity was confirmed with correlation coefficients containing values of -0.84, -0.77 and -0.82 compared to DASH and values ranging from 0.41 to 0.80 compared with the physical domains of the SF-36. The divergent construct validity presented values ranging from 0.07 to 0.20 with the SF-36 domains of "general health perception" and "mental health". The German OES is an internal consistent instrument with good convergent and divergent construct validity. Other aspects of the validity, the reliability and the responsiveness should be confirmed through further studies.


[Artistic anatomy. Introduction to a course of lectures].
The subject-matter and concepts of artistic anatomy are illustrated with reference to its philosophical and psychological aspects.


The roles of cyclic AMP-ERK-Bad signaling pathways on 6-hydroxydopamine-induced cell survival and death in PC12 cells.
The roles of cyclic AMP (cAMP)-ERK1/2-Bad signaling pathways in 6-hydroxydopamine (6-OHDA)-induced cell survival and death were investigated. In PC12 cells, 6-OHDA (10-100μM) concentration-dependently increased the intracellular levels of cAMP mediated by the Ca(2+)-CaMKII-adenylyl cyclase system. 6-OHDA at the non-toxic level (10μM) induced transient ERK1/2 phosphorylation and BadSer112 phosphorylation, which maintained cell survival. In contrast, the high levels of cAMP induced by toxic levels (50 and 100μM) of 6-OHDA induced sustained ERK1/2 phosphorylaton and BadSer155 phosphorylation. The cells then moved to cell death process through Bcl2 phosphorylation and caspase-3 activation. BadSer155 phosphorylation by 6-OHDA was inhibited by PKA (H89) and MEK (U0126) inhibitors, indicating that it was mediated via the cAMP-PKA-sustained ERK1/2 system. In SK-N-BE(2)C cells, the non-toxic level of 6-OHDA also showed transient ERK1/2 phosphorylation and BadSer112 phosphorylation, and toxic levels of 6-OHDA exhibited sustained ERK1/2 phosphorylation and BadSer155 phosphorylation. These results suggest that ERK1/2 phosphorylation by 6-OHDA shows biphasic functions on cell survival and death in PC12 cells. It is, therefore, proposed that the cAMP-ERK1/2-Bad signaling pathways incurred by toxic levels of 6-OHDA play a role in dopamine neuron death of animal models of Parkinson's disease.


The comparative synergistic activity of amikacin, gentamicin, netilmicin and azlocillin, mezlocillin, carbenicillin and ticarcillin against Serratia marcescens.
The synergistic activities of netilmicin, gentamicin and amikacin combined with carbenicillin, ticarcillin, azlocillin and mezlocillin were investigated against 32 Serratia marcescens isolates. Synergy could be demonstrated by killing curve technique, isobologram plots as susceptibility data with any of the aminoglycosides and penicillins combinations. No antagonism was shown with any of the combinations. The majority of the isolates were resistant to the aminoglycosides and penicillins. Combination of either ureido-penicillin or carbenicillin with gentamicin or netilmicin did not reduce the MIC values to levels achievable in serum but did reduce the MIC levels of both agents to those achievable in urine. The combination of ureido-penicillins or carbenicillin and ticarcillin with amikacin reduced the inhibitory levels of all isolates to levels achievable in both serum and urine.


Further characterization of the events involved in mitochondrial Ca2+ release and pore formation by prooxidants.
Addition of the prooxidant 3,5-dimethyl-N-acetyl-p-benzoquinone imine (3,5(Me)2NAPQI) to Ca(2+)-loaded mitochondria caused a rapid and extensive release of the sequestered Ca2+. Ca2+ release was accompanied by irreversible NAD(P)H oxidation and was followed by the release of adenine and pyridine nucleotides into the extramitochondrial medium; this is evidence of the opening of the pore in the inner mitochondrial membrane. Preincubation of the mitochondria with ADP, cyclosporin A (CSA), m-iodobenzylguanidine (MIBG) or Mg2+ inhibited the prooxidant-induced Ca2+ release and prevented pore-opening. When mitochondria were preincubated with ruthenium red, Ca2+ release was only minimally stimulated by 3,5(Me)2NAPQI. However, increasing the concentration of the prooxidant caused release of an increasing fraction of the sequestered Ca2+. Alternatively, increasing the intramitochondrial Ca2+ load resulted in a lowering of the concentration of 3,5(Me)2NAPQI required for near complete Ca2+ release to occur. In the presence of ruthenium red, 3,5(Me)2NAPQI-induced Ca2+ release was accompanied by irreversible pyridine nucleotide oxidation and followed by the release of nucleotides into the extramitochondrial medium, events which were prevented on preincubation with CSA. Similarly, the addition of CSA, ADP or MIBG during 3,5(Me)2NAPQI-induced Ca2+ release arrested further Ca2+ release. In addition to their inhibitory effect on the 3,5(Me)2NAPQI-induced Ca2+ release, CSA, ADP or MIBG also decreased the rate of the basal, ruthenium red-induced mitochondrial Ca2+ release by 45-70%. It is proposed that the basal, ruthenium red-induced and the prooxidant-induced mitochondrial Ca2+ release occur through a common component that is sensitive to inhibition by CSA, ADP and MIBG and that is involved in mitochondrial pore formation. Furthermore, 3,5(Me)2NAPQI-induced pore opening does not involve Ca(2+)-cycling, but rather involves a site(s) that is (are) synergistically activated by Ca2+ and the prooxidant.


Mutants of Staphylococcus aureus deficient in recombinational repair. Improved isolation by selecting for mutants exhibiting concurrent sensitivity to ultraviolet radiation and N-methyl-N'-nitro-N-nitrosoguanidine.
Recombination-deficient (rec) mutants of Staphylococcus aureus strains 152 and Ps29 were sought by initially screening mutagenized cultures for mutants exhibiting increased sensitivity to both ultraviolet (UV) radiation and N-methyl-N'-nitro-N-nitrosoguanidine (NG). Mutants thus isolated were analyzed for recombinational ability by transduction, and further characterized in terms of sensitivity to UV, NG, ability to repair UV-irradiated bacteriophage, and spontaneous and UV-induced DNA degradation. Mutagenesis of strain 152 yielded three isolates, one of which was rec, the second potentially lex, and the third possessing an undetermined repair deficiency. Mutagenesis of strain Ps29 resulted in the isolation of one mutant, which exhibited a rec genotype. In searching for rec mutants of S. aureus, the value of initially screening mutagenized cultures for mutants exhibiting concurrent sensitivity to UV and NG, as opposed to screening for UV sensitivity alone, is discussed.


Transplacental effects of a 15% olive-oil diet on chemically-induced tumorigenesis in offspring.
We evaluated whether feeding pregnant female rats a diet high in olive-oil, that showed a tumor-preventive effect in adults, has a similar preventive effect on chemically-induced cancer in offspring (i.e. mammary glands and colon cancer in rats). The control group was fed the same 7% corn-oil diet as their mothers. Experimental group I was fed a 7% corn-oil diet while their mothers received a 15% olive-oil diet. Experimental group II was fed the same 15% olive-oil diet as their mothers. Female offspring were twice administered 7,12-dimethylbenz(a)antracene (DMBA) in doses of 10 mg/rat. Male offspring were injected 6 times with 1, 2-dimethylhydrazine (DMH) in doses of 20 mg/kg body weight. Effect of DMBA was manifested in a high rate of tumorigenesis: the number of tumor-bearing rats in control offspring reached 52.0%. This effect increased to 60.6% among offspring of experimental group II and to 67.7% in offspring of experimental group I. The mean tumor size increased significantly in control offspring. Following administration of DMH number of tumor-bearing rats was similar in all groups of offspring: 36.7%, 40.7% and 42.8%. Tumor types differed: the majority of tumors in the control group were benign polyps and adenomas (72.1%) and the number of adenocarcinomas was low (27.9%). The number of malignant tumors increased to 37.5% in offspring of experimental group II and to 45.5% in offspring of experimental group I. In control group offspring, a distinct tendency to increased body weight and a significant increase in spleen weight were seen. The findings indicate that feeding mothers a diet high in fat concentrations, even those with known tumor preventive significance in adults, lose this cancer-inhibiting role in offspring.


Epidemiology of cerebral malaria and its mortality.
Over the past 5 years, 1620 comatosed patients of both sexes aged 1-75 years were screened for cerebral malaria. Of these, 505 (31.2%) were positive for Plasmodium falciparum. During this period frequency of malaria increased from 22.1% in 1991 to 44.4% in 1995. Sixty-four percent cases of cerebral malaria were seen in children and thirty-six percent in adults. Mortality was also higher (41%) in children than in adults (25%). As cerebral malaria is particularly prevalent in Pakistan and is a major community problem, accurate and easier methods of its diagnosis are needed at primary health care level, in all febrile comatose patients, without focal neurological findings.


High-density lipoprotein and coronary heart disease: lessons from recent intervention trials.
Epidemiologic studies have consistently implicated low plasma high-density lipoprotein cholesterol as an important, independent risk factor for the development of coronary heart disease. However, clinical trials specifically designed to evaluate the role of lipid therapy in patients with low high-density lipoprotein cholesterol have only been recently reported. They include two trials with angiographic end points, the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial, and three clinical end points trials, the Air Force/Texas Coronary Atherosclerosis Prevention study, the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, and the Bezafibrate Infarction Prevention study. These and other trials clearly indicate that persons with coronary heart disease and high low-density lipoprotein cholesterol (>130 mg/dL [3.36 mmol/L]), with or without low high-density lipoprotein cholesterol, benefit from statin therapy. The Air Force/Texas Coronary Atherosclerosis Prevention study showed that persons at high risk of coronary heart disease but without known disease, who have moderate levels of low-density lipoprotein cholesterol as well as low levels of high-density lipoprotein cholesterol, also appear to benefit from statin therapy although the cost effectiveness of this approach is unclear. The results from the Department of Veterans Affairs High Density Lipoprotein Intervention Trial provide convincing evidence that patients without high low-density lipoprotein cholesterol and with established coronary heart disease and low high-density lipoprotein cholesterol benefit from gemfibrozil. This drug may be particularly beneficial for patients who, in addition to low high-density lipoprotein cholesterol, present with other features of the metabolic syndrome, such as obesity, glucose intolerance, and high triglycerides. Whether other fibrates, niacin, or statins lower coronary heart disease risk in persons with low high-density lipoprotein cholesterol in the absence of high or moderately high low-density lipoprotein cholesterol is unknown. (c)2000 by CHF, Inc.


Vascular virtual endoluminal visualization of invasive colorectal cancer on MDCT colonography.
The purpose of this study was to assess the utility of vascular views for visualization of invasive colorectal cancers on contrast-enhanced MDCT colonography. By means of Hounsfield-transparency settings, we obtained virtual endoluminal images that show vascular structures and delineate invasive cancers of the colorectal wall, and we call these images "vascular views." Using this technique for contrast-enhanced MDCT colonography, we found that the increase in flow and pooling of blood related to angiogenesis of cancerous lesions is easy to identify and that this finding is useful in the detection of invasive colorectal cancers.


Should blunt arterial trauma to the extremities be treated with endovascular techniques?
Endovascular techniques are making progress in most aspects of vascular disease. Penetrating or blunt trauma to large arteries can in many cases be managed elegantly with endovascular techniques. However when it comes to arterial trauma of the extremities things are more complicated. There are no reports hitherto in the literature on endovascular treatment of blunt injuries to the arteries of the extremities. In the present report we describe two cases of blunt trauma to the brachial artery treated with balloon angioplasty (PTA) to fixate the dissected intima to the vessel wall. The "glueing" was effective in giving a long lasting patency.We anticipate that there may be a role, though limited, for using PTA as a means of "glueing" the intima. More advanced techniques such as insertion of stents or stent-grafts in traumatized extremity arteries would rarely be indicated.


Antagonists to the Wnt cascade exhibit sex-specific expression in gonads of sexually mature shovelnose sturgeon.
Little is known regarding molecular mechanisms involved in sex determination and differentiation in sturgeon species. We addressed this knowledge gap by using next generation pyrosequencing technology to provide transcript libraries and species-specific sequences for mature gonads of shovelnose sturgeon, Scaphirhynchus platorynchus. We then mined these libraries to identify gender-specific transcripts and quantified relative transcript abundance using quantitative real-time polymerase chain reaction (qPCR). We detected a limited number of genes known to play a role in sex differentiation in other species. The sequence for dmrt1 was found only in the testes library. The abundance of dmrt1 differed slightly between the sexes, but the melt curve suggests that there may be different isoforms of dmrt1 in ovaries and testes of shovelnose sturgeon. The transcription factor foxl2 was 5.3-fold greater in ovaries than in testes. Two antagonists to the Wnt cascade, dickkopf-1 (dkk1) and dapper-1 (dact1), were found only in the ovary library. Results from qPCR indicated that dkk1 and dact1 were upregulated 1,819.1- and 207.5-fold, respectively, in ovaries compared with testes. These results suggest that antagonists to the Wnt cascade may play significant roles in sex differentiation and gonadal development in sturgeon and could serve as sex markers in this group of ancient fish.


Yessotoxin inhibits phagocytic activity of macrophages.
Yessotoxin (YTX) is a sulphated polyether compound produced by some species of dinoflagellate algae, that can be accumulated in bivalve mollusks and ingested by humans upon eating contaminated shellfish. Experiments in mice have demonstrated the lethal effect of YTX after intraperitoneal injection, whereas its oral administration has only limited acute toxicity, coupled with an alteration of plasma membrane protein turnover in the colon of the animals. In vitro studies have shown that this effect is due to the inhibition of endocytosis induced by the toxin. In this work, we investigated the effects of YTX on phagocytosis by using the J774 macrophage cell line. We found that macrophages exposed to 10 or 1 nM YTX display a reduced phagocytic activity against Candida albicans; moreover, phagosome maturation is also inhibited in these cells. Such results were confirmed with resident peritoneal macrophages from normal mice. The inhibition of both phagocytosis and phagosome maturation likely involves cytoskeletal alterations, since a striking rearrangement of the F-actin organization occurs in YTX-treated J774 macrophages. Surprisingly, YTX also enhances cytokine production (TNF-alpha, MIP-1alpha and MIP-2) by J774 macrophages. Overall, our results show that low doses of YTX significantly affect both effector and secretory functions of macrophages.


R2eD AVM Score.
Background and Purpose- The management of unruptured brain arteriovenous malformations remains unclear. Using a large cohort to determine risk factors predictive of hemorrhagic presentation of arteriovenous malformations, this study aims to develop a predictive tool that could guide hemorrhage risk stratification. Methods- A database of 789 arteriovenous malformation patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model validation was used, whereby the data was randomly split in half into training and validation data sets. Factors significant at the univariable level in the training data set were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves on the training, validation, and complete data sets. The predictors and the complete data set were then used to derive a risk prediction formula and a practical scoring system, where every risk factor was worth 1 point except race, which was worth 2 points (total score varies from 0 to 6). The factors are summarized by R2eD arteriovenous malformation (acronym: R2eD AVM). Results- In 755 patients with complete data, 272 (36%) presented with hemorrhage. From the training data set, a model was derived containing the following risk factors: nonwhite race (odds ratio [OR]=1.8; P=0.02), small nidus size (OR=1.47; P=0.14), deep location (OR=2.3; P<0.01), single arterial feeder (OR=2.24; P<0.01), and exclusive deep venous drainage (OR=2.07; P=0.02). Area under the curve from receiver operating curve analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete data sets, respectively. In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6). Conclusions- The final model derived from this study can be used as a predictive tool that supplements clinical judgment and aids in patient counseling.


Expression of bone formation-related molecules in a newly established protein-independent osteosarcoma.
Protein-independent cells are useful for analysis of proteins that are produced by the cells themselves without any consideration of exogenous proteins. This experimental protein-independent tumor system provides new biology of the autonomous nature of neoplastic cells during their evolution. We established a Dunn protein-free osteosarcoma (DPF) cell line, which was derived from parental fetal calf serum (FCS)-dependent murine Dunn osteosarcoma (DOS) cells. The DPF cells grew in a chemically defined protein-free medium at the high seeding density of 1x10(4) cells/well of a 96-well-plate with a similar doubling time to that of cells growing in the presence of FCS, while the cells did not grow at a density lower than 1x10(3)/well. Furthermore, addition of conditioned medium stimulated the growth in a dose-dependent manner. In contrast, DOS did not grow in the protein-free condition at all. Morphological examination revealed that DPF cells exhibited a more round shape than DOS cells. RT-PCR analysis exhibited the augmentation of the RNA message of bone morphogenetic protein-4 (BMP-4) and osteocalcin in DPF cells. Enhanced expression of BMP-4 protein was also demonstrated by immunoblot analysis. Furthermore, alkaline phosphatase (ALP) activity was higher in DPF cells, indicating that bone-formation related molecules may be overexpressed in protein-independent osteosarcoma cells. These results suggest that putative growth factors may play a role in the DPF cell growth in an autocrine fashion, and the acquisition of autonomous growth independent of exogenous proteins may be coupled to the osteogenic differentiation.


Feasibility of the extracardiac conduit Fontan procedure in patients weighing less than 10 kilograms.
The extracardiac conduit Fontan procedure has led to improved outcomes. We performed the procedure in patients weighing less than 10 kg and evaluated its feasibility. Since January 1999, 72 patients weighing less than 20 kg underwent extracardiac conduit Fontan procedure with polytetrafluoroethylene conduits. The patients were divided into 2 groups: 36 patients weighing less than 10 kg in group S and 36 weighing more than 10 kg in group L. Mean weight, median age, and median follow-up period in groups S and L were 8.5 +/- 1.1 and 14.0 +/- 3.0 kg, 18.9 and 42.0 months, and 29.2 (1.7-79.7) and 42.1 (2.8-94.2) months, respectively. Postoperatively, most patients received peritoneal drainage catheters. We reviewed data precatheterization and postcatheterization and postoperative course. Conduit sizes in groups S and L were 17.0 +/- 1.3 and 17.9 +/- 1.9 mm, respectively (P = .03). Five patients required fenestrations. There were 2 hospital deaths, 1 in each group, and 2 late deaths in group S. The postoperative course was identical in both groups, except for median length of stay in the intensive care unit and peritoneal drainage volume. Group S versus L: ventilator support, 11 versus 7 hours; pleural drainage, 9 days each; pleural drainage greater than 14 days, 6 versus 5 cases; peritoneal drainage, 8 versus 7 days; intensive care unit stay, 7 versus 4 days (P = .01), peritoneal drainage volume, 26.1 versus 14.1 mL x kg x d(-1) (P = .0007). The early outcome of the extracardiac conduit Fontan procedure was satisfactory in patients weighing less than 10 kg. However, the required size of the conduit remains debatable.


Cardiac and noncardiac atrial natriuretic factor (ANF) biosynthesis and storage and plasma ANF in the rat model of chronic ventricular dysfunction.
To evaluate the role of atrial natriuretic factor (ANF) in chronic heart failure (HF), the biosynthesis and storage of ANF in cardiac and noncardiac tissues and the level of plasma ANF were measured in rats exhibiting minimal [2-fold rise in left ventricular end diastolic pressure; myocardial infarct (MI) scar length, 25% left ventricle (LV)] and moderate-severe (3-fold rise in left ventricular end diastolic pressure; decreased contractility (dp/dtmax); MI scar length, 47% LV) chronic HF 30 and 60 days after coronary arterial ligation. In rats with moderate-severe HF (30 days post-MI), the cardiac ANF mRNA concentration (determined by dot blot analysis) increased in three heart chambers [LV, 6-fold; left atria (LA), 3-fold; right ventricle (RV), 2-fold], cardiac immunoreactive ANF (IRANF; determined by RIA) concentration increased on the left side (LV, 7-fold; LA, 33%), but was unchanged (RV) or reduced on the right side (right atria, 33%), and plasma IRANF increased 3-fold above sham control values. Excluding the LV (used for MI scar length), the pattern and magnitude of change in ANF mRNA concentration in moderate-severe HF at 60 days were similar to those at 30 days; the cardiac IRANF concentration at this time was the same (LA) or less than (RV, 66%) sham values, and plasma IRANF increased 6-fold above respective sham values. Generally, the changes in the concentrations of cardiac ANF message and peptide and levels of circulating ANF peptide were smaller in rats with minimal HF. The minute quantities of ANF mRNA and IRANF detected in noncardiac tissues (lung, liver, pituitary, aortic arch, brain, kidney, and salivary gland) were unaltered by HF. These findings show that chronic HF, as defined by hemodynamic and histological measurements, specifically and continuously stimulates atrial as well as ventricular ANF biosynthesis; levels of plasma and cardiac ANF are increased early in HF, but with time are subject to modulation. The cardiac ANF system is the prime locus for the effects of HF, as noncardiac ANF biosynthesis and storage are undisturbed by chronic HF.


[Superficial pyoderma requiring oral antibiotic therapy: fusidic acid versus pristinamycin]].
This study was aimed to compare the clinical and antibacterial efficacy of fusidic acid 500 mg twice a day, per os, over 7.5 days) to pristinamycin 1 g twice a day, per os, over 10 days). Patients aged over 18, suffering from a superficial pyoderma requiring antibiotherapy and having given their informed consent were enrolled in a controlled, multicentre, double blind double dummy, parallel groups study. From day 0 to day 10, the patients received the randomised treatment. Those who were cured at day 11 had a visit at day 25 without any treatment between day 11 and day 25. A swab was performed on days 0, 11 and 25. The two treatment groups were compared in terms of efficacy, safety and global cost. 334 patients seen in dermatologic consultation were included in the study. 313 patients were analysed on an intent-to-treat basis. 158 received fusidic acid (FA) and 155 were treated with pristinamycin (P). At D11, 126 patients were cured in the FA group (79.7%) and 118 in the P group (76.1%) (p = 0.44). The bacteriological success rate was 85.2% in the FA group and 82.7 in the P group (p = 0.67). The recovery was confirmed in 92.6% of the FA patients and 90.4% of the P patients at D25 (p = 0.56). Digestive tolerance was better with fusidic acid than with pristinamycin. In economic terms, fusidic acid was cheaper than pristinamycin: 443 French francs in the FA group versus 545 FF in the P group. Therefore we conclude that an oral course of 7.5 days with fusidic acid is an efficient and cheaper alternative to a treatment with pristinamycin over 10 days.


Discriminant Analyses Of Preschool Masculinity And Femininity.
The nature of masculinity and femininity in the preschool years was investigated. Four criterion groups, Most Masculine boys, Least Masculine boys, Most Feminine girls, and Least Feminine girls, were selected from teachers' judgments of masculinity and femininity made by the method of pair comparisons. A covariance matrix of the teachers' personality ratings of these children was factor analyzed. Four factors were identified : Extraversion- Introversion, Social Adjustment, Competence, and an unnamed factor. A discriminant analysis on these factors indicated that MM boys were more extraverted, somewhat more competent and slightly more socially adjusted than LM boys. A second discriminant analysis indicated that M F girls were more socially adjusted, somewhat more competent and slightly more introverted than LF girls. The coefficient of congruence between the discriminant pat- terns for masculinity and femininity indicated that these constructs are not opposite ends of a continuum.


Does hybrid fixation prevent junctional disease after posterior fusion for degenerative lumbar disorders? A minimum 5-year follow-up study.
Medium- to long-term retrospective evaluation of clinical and radiographic outcome in the treatment of degenerative lumbar diseases with hybrid posterior fixation. Thirty patients were included with the mean age of 47.8 years (range 35 to 60 years). All patients underwent posterior lumbar instrumentation using hybrid fixation for lumbar stenosis with instability (13 cases), degenerative spondylolisthesis Meyerding grade I (6 cases), degenerative disc disease of one or more adjacent levels in six cases and mild lumbar degenerative scoliosis in five patients. Clinical outcomes were evaluated using Oswestry disability index (ODI), Roland and Morris disability questionnaire (RMDQ), and the visual analog scale (VAS) pain scores. All patients were assessed by preoperative, postoperative and follow-up standing plain radiographs and lateral X-rays with flexion and extension. Adjacent disc degeneration was also evaluated by magnetic resonance imaging (MRI) at follow-up. At a mean follow-up of 6.1 years, we observed on X-rays and/or MRI 3 cases of adjacent segment disease (10.0 %): two of them (6.6 %) presented symptoms and recurred a new surgery. The last patient (3.3 %) developed asymptomatic retrolisthesis of L3 not requiring revision surgery. The mean preoperative ODI score was 67.6, RMDQ score was 15.1, VAS back pain score was 9.5, and VAS leg pain score was 8.6. Postoperatively, these values improved to 28.1, 5.4, 3.1, and 2.9, respectively, and remained substantially unchanged at the final follow-up: (27.7, 5.2, 2.9, and 2.7, respectively). After 5-year follow-up, hybrid posterior lumbar fixation presented satisfying clinical outcomes in the treatment of degenerative disease.


Effect of static pressure on the disappearance rate of specific echocardiographic contrast agents.
Contrast echocardiography has been applied to identify cardiac structures, shunts, and perfusion territories. Most recently, quantification of flow has been proposed based on disappearance of contrast intensity. This requires that contrast agents are stable and produce a predictable effect. To assess the possible effect of pressure on their stability, the rates of backscatter decay of four echocardiographic contrast agents (Albunex, Levovist, agitated Angiovist, and agitated saline solution) exposed to constant pressures (0, 50, 100, 150, and 200 mm Hg) were quantitated. Contrast was recorded by echocardiography and measured to construct time-intensity curves. The peak decay rate for each agent at each pressure was determined. For all four agents, contrast intensity (I) decreased over time and could be described by the sigmoid function: I = a [e-lambda(t-ts)/1 + e-lambda(t-ts)] + C. Peak decay rate was significantly affected by pressure (p < 0.005) in a proportionate fashion. At pressures of 0, 100, and 200 mm Hg, the rates increased for each agent in the following fashion: Albunex, 0.144 +/- 0.109 to 0.410 +/- 0.142 to 1.442 +/- 0.309; Levovist, 0.060 +/- 0.023 to 0.162 +/- 0.049 to 0.495 +/- 0.142; Angiovist, 0.089 +/- 0.028 to 0.166 +/- 0.057 to 0.224 +/- 0.027; and saline solution, 0.068 +/- 0.039 to 0.110 +/- 0.036 to 0.154 +/- 0.057. The effect of pressure on the peak rate of contrast disappearance (lambda) was significantly different among agents (p < 0.001). Thus attempts to quantitate blood flow with contrast agents must take into account the influence of pressure.


Effects of 2 brief interventions on women's understanding of moderate-intensity physical activity.
Women's understanding of "moderate-intensity" physical activity (MPA) as presented in the media is not well-understood. This study assessed whether women who are presented a mass-media message about MPA can demonstrate a moderate-intensity walking pace without practicing this pace first. Insufficiently active women (n = 75, age 40 +/- 12 years, 76% White) were shown a mass-media description of a MPA recommendation. Forty-one were randomized to also practice a moderate-intensity (55%-70% of maximum heart rate) walk. One month later, participants were asked to demonstrate a 10-minute moderate-intensity walk. Groups were compared on the proportion of participants who walked > or = 10 minutes at a moderate intensity. At posttest, more participants who received practice at baseline walked at a moderate-intensity > or = 10 minutes than those who received no practice (P < .05). To understand MPA, it is not enough to simply hear and read a description of MPA. It is essential to practice MPA.


Long-Term Efficacy of Oral Vancomycin Prophylaxis for the Prevention of Clostridium difficile Recurrence.
Limited evidence suggests that prophylactic oral vancomycin may be beneficial in preventing Clostridium difficile infection (CDI) recurrence, but long-term efficacy is unknown. To evaluate the long-term efficacy of oral vancomycin prophylaxis (OVP) in preventing CDI recurrence in subjects who require subsequent antibiotic exposure. A retrospective cohort study was conducted at a community hospital. A total of 91 subjects with a history of CDI between January 2013 and December 2015 who had a subsequent hospitalization requiring systemic antibiotics within 12 months were evaluated. Thirty-two subjects who received prophylaxis with oral vancomycin were compared to 59 subjects who did not receive prophylaxis. CDI recurrence within 12 months was significantly lower in subjects receiving OVP compared to those who did not receive OVP (6.3% vs 28.8%; odds ratio [OR]: 0.16; 95% confidence interval [CI]: 0.04-0.77; P = .011) including patients whose previous CDI was an initial episode (3.7% [1/27] vs 28.3% [15/53]; OR: 10.3; 95% CI: 1.28-82.6; P = .009). Use of OVP in subjects with a history of CDI up to 12 months prior to subsequent antibiotic exposure appears to reduce the risk of CDI recurrence for up to 12 months.


Association Assessment among Risk Factors and Breast Cancer in a Low Income Country: Bangladesh.
In the low incoming country Bangladesh, breast cancer is second most common neoplasm and is increasing at an alarming rate among females. Lack of awareness and illiteracy are contributory factors for late presentation and therefore mortality. To examine associations of different factors with breast cancer mortality and to raise awareness among the women of society in Bangladesh. This descriptive case-control study was conducted on 160 participants from April 2011 till July 2014. Through a valid questionnaire covering personal and family history, data were collected by face to face interview. For analyzing correlations among factors with breast cancer data, binary logistic regression, Pearson's χ2- value, odd ratios and p-value tests were conducted with SPSS version 20. The mean age of the patients was 43.0 (SD= ± 11.12). In ascending order the leading significant factors were hormone therapy (p<0.0000, OR=4.897), abortion (p<0.0001, OR=3.452), early start menarche (p<0.0002, OR=3.500), family history (p<0.0022, OR=3.235), and late menopause (p<0.0093, OR=3.674) with both χ2 test and logistic regression analyses. Non-significant factors were cancer experience, fatty food habits, marital status and taking alcohol. Regarding the investigation of this study, significant and insignificant factor's correlation visualization with breast cancer will be helpful to increase awareness among Bangladeshi women as well as all over the world.


[Short-term outcomes of robot-assisted transanal total mesorectal excision].
To explore the feasibility and safety of Da Vinci robot-assisted transanal total mesorectal excision (taTME). From May 2017 to July 2018, six rectal cancer patients underwent Da Vinci robot-assisted taTME at our hospital. The clinical data and short-term follow-up results were retrospectively analyzed. The patient was placed in a Trendelenburg lithotomy position and sutured with purse string 1-2 cm from the anus to the distal end of the tumor. A self-made platform for transanal surgery was installed and the robot was connected. The rectum was transected circumferentially 0.5 cm from the distal end of the purse. The robot entered the " holy plane" and separated upward between the visceral parietal fasciae to the level of the third sacrum posteriorly and the peritoneal refcection anteriorly. The abdominal trocar was repositioned and connected to the robot. Through the abdominal cavity, the Toldt space of the posterior sigmoid mesentery was entered, and the D3 lymph nodes were dissected proximally. Separation was performed distally to join the perineal approach. Specimen was pulled out from the anus and excised. The cut end of sigmoid colon was anastomosed with the distal rectum or anal canal. Operative status, postoperative pathology and short-term efficacy were analyzed. Mesorectum of specimen was evaluated as complete, near complete and incomplete according to the Nagtegaal criteria. Anastomotic leakage was evaluated according to the criteria developed by the International Rectal Cancer Research Group. All the 6 patients received Da Vinci robot-assisted taTME and sigmoid-anal anastomosis. In the 6 patients, 3 were male and 3 female; mean age was (62.6±2.6) years old; body mass index was (20.5±3.0) kg/m2; distance from tumor to anal edge was (39.4±12.0) mm; length of tumor was (33.6±9.2) mm. Four patients received neoadjuvant therapy before surgery. All the patients completed operations successfully without conversion to laparotomy perioperative, severe complications or death. The mean total operative time was (245.8±24.2) minutes; transition interval of two procedures was (21.2±2.6) minutes; time of transanal robotic dissection of mesorectum was (72.3±15.2) minutes; intra-operative blood loss was (86.7±59.9) ml; the height of anastomosis was (16.0±6.1) mm. There were no intra-operative complications including accidental hemorrhage or urethral injury in any patients. The length of the specimens was (177.0±33.3) mm, and the mesorectum was complete in 5 cases, and near complete in 1 case. The mean distal margin was (20.2±3.2) mm, and the proximal, distal and circumferential margins were all negative. Postoperative pathological staging: T0N0 in 1 case, T0N1 in 1 case , T2N0 in 2 cases , T4N1 in 1 case, T3N0 in 1 case. The former 5 cases received clear fluit diet on the first day, and received fluid diet on the second day after operation. The drainage tube was removed 3 to 6 days after operation. The postoperative hospital stay was 5 to 7 days. The sixth case developed grade B anastomotic leakage on the third day after operation and healed by conservative treatment. No postoperative death, and no serious complications such as intra-abdominal hemorrhage, intestinal obstruction were found. All the patients were followed up for 5 to 19 months, and no local recurrence and death were observed. The robotic system is safe and feasible for taTME procedure in rectal cancer with good short-term efficacy. However, the long-term outcomes require further observation.


Blindness in the intensive care unit: possible role for vasopressors?
Blindness caused by ischemic optic neuropathy in the hospital setting occurs perioperatively and in critically ill patients, but its etiology remains ill defined. We describe four critically ill patients who developed blindness within 1 mo of one another. Three cases occurred outside of the operative arena. Potential risk factors for the development of ischemic optic neuropathy, such as use of vasopressors, venous congestion, and hypotension, are described.


The impact of multimodality therapy of distal esophageal and gastroesophageal junction adenocarcinomas on treatment-related toxicity and complications.
The benefit of multimodality therapy is clearly established for adenocarcinomas of the distal esophagus and gastroesophageal junction, but its impact on toxicity is not well defined. We reviewed data from prospective randomized trials to better define the risks of multimodality therapy. The rates of surgical mortality and complications range from 0% to 10% and 23% to 49%, respectively. Multimodality therapy increases acute toxicity. The rate of severe acute hematologic toxicity varies considerably between trials (3%-78%) and appears to be primarily attributable to chemotherapy. Common severe acute nonhematologic toxicities include esophagitis (16%-63%), infection (2%-30%), pain (3%-24%), and gastrointestinal (6%-60%) and cardiac (3%-19%) events. The individual contribution of each modality to nonhematologic toxicities is unclear, but toxicity is increased when adding radiosensitizing chemotherapy to radiotherapy. There is an acute decrease in quality of life with multimodality therapy; however, quality of life usually returns to, or exceeds, baseline by 12 months after therapy. Late toxicities are less well defined, but commonly include esophageal, pulmonary, and cardiac toxicities.


Surgery for Obesity- An Update of a Randomized Trial.
BACKGROUND: A prospective, randomized trial comparing vertical banded gastroplasty (VBG) and gastric bypass (GB) was performed on 106 patients between 1987 and 1990. METHODS AND RESULTS: Failures of these two operations (manifested by failure to lose weight, late weight gain or intolerance of adequate oral intake) were treated by means of a third operation, isolated gastric bypass (IGB), in which the small gastric pouch was isolated from the gastric fundus. The latter operation was significantly better than VBG or GB and achieved a 63% success rate, i.e. body mass index (BMI) < 35 kg m(2) and less than 50% excess weight. During the year following this trial an additional 54 patients underwent IGB. When this operation was performed for morbid obesity and was the Initial procedure, 96% of the patients achieved a successful result. If IGB was performed as a revision procedure or for super obesity (BMI > 50 kg m(2)), the success rate was 63% with 100% follow-up at 40 months. Major morbidity occurred in six of the 160 patients who underwent 195 operations (the trial period and subsequent year). There were no deaths and follow-up was 98%. CONCLUSIONS: The ideal gastric operation based on this study emphasizes the following requirements: a small pouch (< 15 ml) totally separated from the stomach, a pouch not dependent on staples, placed in the dependent position to prevent stasis, constructed without foreign material and with an anastomosis which permits ingestion of solid food.


Algesiogenic and analgesic activities of synthetic substance P.
The objective of our study was to determine whether the pure synthetic substance P(SP) is algesiogenic or analgesic when administered centrally or peripherally. The relationships between SP-induced analgesia and the content of morphine-like factor (MLF) in the brain were also studied. Intracarotid arterial administration of SP (20-200 microgram) produced no pseudoaffective responses to pain in six out of nine rats, but in the remaining three, there was an exhibition of these responses. Chlorpheniramine pretreatment antagonized these responses. On cantharidin blister base experiments in humans, SP (10(-3) g/ml) produced slight pain and an itchy sensation. SP given intracerebroventricularly produced an analgesia in mice in a dose of 5 ng/mouse, as determined by the acetic acid-induced writhing and hot plate methods. These SP-induced analgesia were antagonized by naloxone pretreatment. SP did not alter the content of MLF in the mouse whole brain. However, SP5-11 not only produced an analgesia but also increased the content of MLF. These results suggest that SP has a slight algesiogenic activity which might be mediated by histamine and a slight analgesic activity which might be mediated by MLF.


Risk factors for spontaneous abortion from a prevention perspective in rural China: a population-based follow-up study.
Objectives: We conducted this study to investigate the risk factors for spontaneous abortion among rural Chinese women. Methods: Risk factors prior to pregnancy associated with spontaneous abortion were identified among 17,248 rural women enrolled in a prospective population-based follow-up study. The risk of spontaneous abortion was estimated with odds ratio (OR) and 95% confidence interval (CI) for several factors. A nonconditional logistic regression analysis was then performed to identify the independently associated factors. Results: The total sample of this study population consisted of 17,248 pregnant women including 921 of them whose pregnancies resulted in spontaneous abortion and the incidence of spontaneous abortion was 5.04%. After the adjustment of confounding factors, menarche age, serum creatinine, family genetic diseases or maternal congenital defects was associated with an increased risk of spontaneous abortion while folic acid supplementation reduced the risk among rural Chinese women. Conclusions: The findings of our study suggest that multiple modifiable factors may increase the risk of spontaneous abortion which may help relevant departments better to guide detailed effectively prevention strategies toward spontaneous abortion to improve the reproductive quality of rural population. Further studies are required to elaborate these risk factors for spontaneous abortion.


Asymptomatic anomalous origin of the left coronary artery from the pulmonary artery.
Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital anomaly of the coronary arteries which usually presents with heart failure in early infancy. We describe the unusual occurrence of this in an older child with no signs of cardiac ischemia.


Effects of social class differences and social mobility on growth in height, weight and body mass index in a British cohort.
By longitudinally linking follow-up restudies of the National Child Development Study it has been possible to examine not only the well-known association of social class with the size of the child, but also with longitudinal growth, and, in addition the effect of social mobility on growth. The relation of type of occupation of the male head of household to height and weight of the child is seen at all ages (7, 11 and 16) but class influence on growth from 7 years onward is minimal. Social mobility is a significant factor especially in relation to stature but is not significantly related to growth after age 7 so the effect of underlying conditions on the children precedes the change of type of occupation by their fathers.


Intra-Abdominal Adhesions Make the Interpretation of Magnetic Resonance Enterography in Crohn's Disease More Difficult.
The present study compares preoperative magnetic resonance enterography (MRE) accuracy in diagnosing stenoses, abscesses and fistulas to intraoperative findings in Crohn's disease patients, and determines whether discordance between these methods alter surgical plans. Our study included 55 consecutive patients scheduled for elective surgery due to Crohn's disease in a single institution between January 2011 and May 2015, whose surgical findings were also compared to preoperative MREs. Data were retrospectively analyzed. Among these 55 patients, we found 80 stenoses, 5 abscesses and 18 fistulas during surgery. The MRE sensitivity, specificity and accuracy, respectively, reached 100, 77.8 and 96.4% for stenoses; 80.0, 90.0 and 89.1% for abscesses; and 77.8, 83.8 and 81.8% for fistulas. The operative plan was modified for 7 patients (12.7%) due to erroneous MRE diagnoses. No patient needed conversion or an unplanned stoma placement due to an incorrect diagnosis using MRE. The MRE diagnosis did not agree with the surgical findings for 36 lesions, 16 of which resulted from adhesions that explained the incorrect MRE diagnoses. Hence, while MRE is a useful diagnostic tool preoperatively in Crohn's disease patients, the presence of intra-abdominal adhesions may cause erroneous diagnosis through MRE.


Endoscopic measurement of Barrett's esophagus length is unreliable - a prospective comparative biopsy study.
Endoscopic assessment of the length and area of Barrett's esophagus (BE) has become crucial in assessing its spontaneous course as well as any effect of pharmacological or endoscopic treatment. Little, however, is known about the extent to which the endoscopic assessment of BE length and area correlates with the histopathological confirmation of BE epithelium. 75 consecutive patients (mean age 60 years; 58 men, 17 women) were included in a prospective study on the basis of the endoscopic suspicion of BE. BE was endoscopically defined as gastric-type epithelium between the proximal cardiac folds and the Z line, on moderate air insufflation. Stepwise four-quadrant biopsies (4QB) were then taken, beginning at the proximal cardiac folds and then every 2 cm up to the Z line. Among the 75 study patients, BE was histologically verified in 57 cases (group 1) and not confirmed in any of the endoscopic biopsy samples in 18 cases (group 2). In group 1, the mean difference between the endoscopic and histological assessment of BE length was + 1 cm (range 0 - 5 cm); when determining the BE area histologically from 4QB the mean difference to the endoscopic determination was + 36 % (range 0 - 93 %). These differences were independent of the presence and degree of hiatal hernia or the presence of long or short BE. In the majority of patients, there is only a moderate correlation between the endoscopic and the histological extent of BE. However, we also found a substantial individual variability in endoscopic-histological correlation; therefore studies on the effects of treatment on BE must consider both the endoscopic and histopathological BE lengths.


Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes.
There is a need for noninvasive methods to detect liver steatosis, which can be a factor of liver fibrosis progression. This work aims to evaluate a novel ultrasonic controlled attenuation parameter (CAP) devised to target, specifically, liver steatosis using a sophisticated process based on vibration control transient elastography (VCTE™). CAP was first validated as an estimate of ultrasonic attenuation at 3.5 MHz using Field II simulations and tissue-mimicking phantoms. Performance of the CAP was then appraised on 115 patients, taking the histological grade of steatosis as reference. CAP was significantly correlated to steatosis (Spearman ρ = 0.81, p < 10(-16)). Area under receiver operative characteristic (ROC) curve (AUC) was equal to 0.91 and 0.95 for the detection of more than 10% and 33% of steatosis, respectively. Furthermore, results show that CAP can efficiently separate several steatosis grades. These promising results suggest that CAP is a noninvasive, immediate, objective and efficient method to detect and quantify steatosis.


Interventions for obstructive sleep apnea in children: a systematic review.
Obstructive sleep apnea (OSA) is characterized by habitual snoring, heavy breathing, sleep-related hypoxia and arousals from sleep, and is found in approximately 3% of children. To review the efficacy of medical, behavioral, mechanical and surgical interventions in improving OSA in children. Bibliographic databases, relevant conference proceedings and trial registers were searched. Randomized controlled trials assessing interventions in children with objectively diagnosed OSA (as per polysomnography; apnea/hypopnea index (AHI) or respiratory disturbance index (RDI) > or = 1/h) were considered. The search identified 1690 potentially relevant studies. The five trials that met the inclusion criteria investigated seven different interventions (intranasal steroids, adenotonsillectomy, maxillary distraction, temperature-controlled radiofrequency ablation, oral appliances, continuous and bilevel positive airway pressure therapy). Intranasal steroids had a significant advantage over placebo in decreasing the AHI (one study). Temperature-controlled radiofrequency ablation and adenotonsillectomy were equally effective in reducing the RDI (one study). Continuous and bilevel positive airway pressure therapy was equally effective in reducing the AHI (one study). There was insufficient evidence to support the use of oral appliances. Despite a broad array of treatment options for OSA, there is limited evidence to support their use. More research is needed before general recommendations can be made.


Accurate Interactive Visualization of Large Deformations and Variability in Biomedical Image Ensembles.
Large image deformations pose a challenging problem for the visualization and statistical analysis of 3D image ensembles which have a multitude of applications in biology and medicine. Simple linear interpolation in the tangent space of the ensemble introduces artifactual anatomical structures that hamper the application of targeted visual shape analysis techniques. In this work we make use of the theory of stationary velocity fields to facilitate interactive non-linear image interpolation and plausible extrapolation for high quality rendering of large deformations and devise an efficient image warping method on the GPU. This does not only improve quality of existing visualization techniques, but opens up a field of novel interactive methods for shape ensemble analysis. Taking advantage of the efficient non-linear 3D image warping, we showcase four visualizations: 1) browsing on-the-fly computed group mean shapes to learn about shape differences between specific classes, 2) interactive reformation to investigate complex morphologies in a single view, 3) likelihood volumes to gain a concise overview of variability and 4) streamline visualization to show variation in detail, specifically uncovering its component tangential to a reference surface. Evaluation on a real world dataset shows that the presented method outperforms the state-of-the-art in terms of visual quality while retaining interactive frame rates. A case study with a domain expert was performed in which the novel analysis and visualization methods are applied on standard model structures, namely skull and mandible of different rodents, to investigate and compare influence of phylogeny, diet and geography on shape. The visualizations enable for instance to distinguish (population-)normal and pathological morphology, assist in uncovering correlation to extrinsic factors and potentially support assessment of model quality.


Characterization of a 5HS-7DS.7DL wheat-barley translocation line and physical mapping of the 7D chromosome using SSR markers.
A spontaneous wheat-barley translocation line was previously detected in the progenies of the Mv9kr1 × 'Igri' wheat-barley hybrid and the translocation was identified as 5HS-7DS.7DL. Multicolor genomic in situ hybridization (mcGISH) with D and H genomic DNA probes and three-color fluorescence in situ hybridization (FISH) with repetitive DNA probes (Afa-family, pSc119.2, and pTa71) were performed to characterize the rearranged chromosome. The effect of 5HS and the deleted 7DS fragment on the morphological traits (plant height, fertility, yield, and spike characteristics) of wheat was assessed. Despite the non-compensating nature of the translocation, the plants showed good viability. The aim of the study was to physically localize SSR markers to the telomeric and subtelomeric regions of the 7DS chromosome arm. Of the 45 microsatellite markers analyzed, ten (Xbarc0184, Xwmc0506, Xgdm0130, Xgwm0735, Xgwm1258, Xgwm1123, Xgwm1250, Xgwm1055, Xgwm1220, and Xgwm0635) failed to amplify any 7DS-specific fragments, signaling the elimination of a short chromosome segment in the telomeric region. The breakpoint of the 5HS-7DS.7DL translocation appeared to be more distal than that of reported deletion lines, which provides a new physical landmark for future deletion mapping studies.


Expression of aquaporin water channels in rat taste buds.
In order to gain insight into the molecular mechanisms that allow taste cells to respond to changes in their osmotic environment, we have used primarily immunocytochemical and molecular approaches to look for evidence of the presence of aquaporin-like water channels in taste cells. Labeling of isolated taste buds from the fungiform, foliate, and vallate papillae in rat tongue with antibodies against several of the aquaporins (AQPs) revealed the presence of AQP1, AQP2, and AQP5 in taste cells from these areas. AQP3 antibodies failed to label isolated taste buds from any of the papillae. There was an apparent difference in the regional localization of AQP labeling within the taste bud. Antibodies against AQP1 and AQP2 labeled predominantly the basolateral membrane, whereas the AQP5 label was clearly evident on both the apical and basolateral membranes of cells within the taste bud. Double labeling revealed that AQP1 and AQP2 labeled many, but not all, of the same taste cells. Similar double-labeling experiments with anti-AQP2 and anti-AQP5 clearly showed that AQP5 was expressed on or near the apical membranes whereas AQP2 was absent from this area. The presence of these 3 types of AQPs in taste buds but not in non-taste bud-containing epithelia was confirmed using reverse transcription-polymerase chain reaction. Experiments using patch clamp recording showed that the AQP inhibitor, tetraethylammonium, significantly reduced hypoosmotic-induced currents in rat taste cells. We hypothesize that the AQPs may play roles both in the water movement underlying compensatory mechanisms for changes in extracellular osmolarity and, in the case of AQP5 in particular, in the gustatory response to water.


[Treatment of fractures of the base of the finger tip (Busch's injury)].
The validity of surgical treatment about "Mallet finger" with avulsion of tendon insertion (Bush lesion's) is presented. Are exposed 25 cases treated from 1980 to January 1983 with optimal results.


Ontogeny and effects of thyroid hormone on beta1-adrenergic receptor mRNA expression in ovine fetal kidney cortex.
Previous studies indicate that thyroidectomy (TX) decreases renin gene expression in ovine fetal renal cortex in late gestation. Fetal ovine renin-containing renocortical cells become increasingly responsive to beta-adrenergic stimulation as gestation proceeds. Increases in plasma thyroid hormone concentrations parallel this change, suggesting that there is a positive developmental relationship between the two. To examine this hypothesis, we determined the ontogeny of beta1-adrenergic receptor (beta1R) mRNA expression, and the effect of thyroid hormone on in vivo and in vitro expression in fetal sheep. Renocortical tissue was obtained from naive, TX, and sham-operated fetuses to determine beta1R mRNA levels. Renin-containing renocortical cells from TX or sham fetuses were treated with isoproterenol (Iso) or forskolin (FSK) for analysis of cellular cyclic adenosine monophosphate (cAMP) levels. Renocortical cells from naive fetuses were treated with triiodothyronine (T3) to assess cellular beta1R mRNA levels. Fetal plasma thyroxine (T4) level was determined. Renocortical beta1R mRNA expression increased significantly between 100 and 140 days' gestational age (dGA), while TX attenuated this increase (P <.01). Renocortical cellular cAMP levels were higher in sham compared to TX fetuses following incubation with Iso or FSK (P <.05). Cells incubated with T3 exhibited significantly increased beta1R mRNA expression (P <.05). The data suggest that thyroid hormone may be involved in modulating ovine fetal renocortical beta1R gene expression during development. We speculate that the increased beta1R mRNA expression in renal cortical cells as development progresses may mediate the increases in renin gene response to beta-adrenergic stimulation in late gestation.


Two new polymorphisms in the coding sequence of the LDL receptor (LDLR) gene.
We identified by polymerase chain reaction/single-strand conformation polymorphism analysis two unreported polymorphisms in the low density lipoprotein receptor gene, located in exons 11 and 15. The exon 15 sequence variation can also be readily detected since it abolishes an MspI site.


Medicine and nursing in the Spanish Civil War: women who served in the health services of the International Brigades (1936-1939).
The outbreak of the Spanish Civil War in 1936 had repercussions throughout the world. Even though Western democracies had signed a Non-Intervention Agreement, thousands of foreign volunteers fought on the Republican side. This paper briefly summarizes the issues that directly led to the war, and focuses on the intervention of the International Brigades, the origins of the International Sanitary Service (ISS) and the role played by women at the ISS. These women implemented and collaborated in important and innovative procedures in military medicine, that we analyze below.


Modified model for the regulation of the tryptophan operon in Escherichia coli.
This article proposes a modification of the model developed by Sinha (1988) and Sen and Liu (1990) for the regulation dynamics of the tryptophan operon in E. coli based on a consistent overall balance of the agent repressing the mRNA transcription. The dynamics of the model are analyzed by means of continuation techniques and the influence of periodic fluctuations in the intracellular demand for tryptophan is addressed. The analysis provides deeper insight into the dynamics of this operon system and the results obtained may be a useful starting point for the optimization of tryptophan yield in bacterial cultures.


The therapeutic efficacy of endoscopic optic nerve decompression and its effects on the prognoses of 96 cases of traumatic optic neuropathy.
Traumatic optic neuropathy (TON) is an important cause of severe loss of vision due to blunt or penetrating head trauma. The pathogenesis of TON remains unclear, and there are several potential causes for the observed loss in vision. Endoscopic optic nerve decompression (EOND) has been reported to improve the visual prognosis in TON cases, but its efficacy remains controversial. It is important to investigate the therapeutic efficacy of EOND in the treatment of TON and to evaluate the relevant prognostic factors. A retrospective study was conducted to analyze the clinical characteristics and prognoses of 96 TON cases. The χ(2) test and multiple logistic regression analyses were used to evaluate potential prognostic factors. : The overall rate of EOND effectiveness was 40.6% (39 of 96). A significantly higher effective rate (83.3%) was observed for patients with light perception compared with those without light perception (26.4%, p < 0.05). Univariate and multiple logistic regression analyses identified three variables (no light perception, undergoing EOND 3 days after trauma, and hemorrhage within the ethmoid and/or sphenoid sinus) that were significantly associated with unrecovered visual acuity. Age, loss of consciousness, optic canal fracture, preoperative steroid megadose treatment, and optic nerve sheath incision were all factors that showed no significant correlation with therapeutic efficacy. However, patients with fractures in a single medial wall of the optic canal appeared to have better prognoses than patients with multiple fractures or those with a single fracture in a lateral wall. The overall therapeutic efficacy of EOND for the treatment of TON is far from satisfactory, especially for patients without light perception. The factors that impact TON prognoses are complex and may be interrelated. The indication for EOND must be individualized. III, epidemiological study.


[Leg edema detected on comprehensive geriatric assessment for elderly outpatients and its associated risk factors].
Leg edema, observed on comprehensive geriatric assessment (CGA) of 142 elderly outpatients with a variety of chronic diseases, was studied clinically to clarify its incidence and its associated risk factors. The severity of pitting edema was assessed at 3 points, namely, the pretibial edge, medial malleolus, and the dorsum of the foot. On palpation, edema was graded as 0 to 3 for each point on one leg, the sum of which was used as the edema score. According to the edema score, subjects were divided into 3 groups; the moderate to severe (MS) group, the slight to mild (SM) group, and the group without pitting edema. The MS group was defined as having an edema score of 4 or more or edema of grade 2 or more, while the SM group was defined as having an edema score of 2 to 3 points without edema of grade 2 or more. The status of underlying disease, vascular risks, varicose veins, medications, daily activity, nutrition, total protein (TP), albumin, brain natriuretic peptide (BNP), and the estimated glomerular filtration rate (eGFR) were compared among the 3 groups. There were 36 subjects in the MS group and 19 subjects in the SM group. Diabetes, atrial fibrillation, varicose veins, and polypharmacy were more frequent in the MS group than in the control group. Sedentary life style, house-bound, and gait trouble were significantly more frequent in the MS and SM groups. There were no significant differences in the scores of the Mini-Nutritional Assessment Short Form among the groups, although both the body weight and calf circumference in the MS group were significantly greater than those in the group without pitting edema. Low serum TP, albumin and eGFR were seen in the MS group as well as high BNP levels. Multiple regression analysis revealed diabetes, varicose veins, sedentarism, and hypoalbuminemia as risk factors associated with leg edema (R(2)=0.365, p<0.0001). Leg edema was frequent in the elderly outpatients and was associated strongly with diabetes, varicose veins, sedentarism, and hypoalbuminemia. These findings suggest that advising against a sedentary life style could help the resolution of edema, and also indicates the clinical usefulness of CGA. Furthermore, leg edema should be seriously considered along with nutritional assessment because edema could influence various anthropometric parameters.


Photoperiodic regulation of leptin sensitivity in the Siberian hamster, Phodopus sungorus, is reflected in arcuate nucleus SOCS-3 (suppressor of cytokine signaling) gene expression.
We present the first evidence that suppressor of cytokine signaling-3 (SOCS3), a protein inhibiting Janus kinase/signal transducer and activator of transcription (STAT) signaling distal of the leptin receptor, conveys seasonal changes in leptin sensitivity in the Siberian hamster. Food deprivation (48 h) reduced SOCS3 gene expression in hamsters acclimated to either long (LD) or short (SD) photoperiods, suggesting that leptin signals acute starvation regardless of photoperiod. However, SOCS3 mRNA levels were substantially lower in the hypothalamic arcuate nucleus of hamsters acclimated to SD than in those raised in LD. In juveniles raised in LD, a rapid increase in SOCS3 mRNA was observed within 4 d of weaning, which was completely prevented by transfer to SD on the day of weaning. The early increase in SOCS3 gene expression in juvenile hamsters in LD clearly preceded the establishment of different body weight trajectories in LD and SD. In adult LD hamsters, SOCS3 mRNA was maintained at an elevated level despite the chronic food restriction imposed to lower body weight and serum leptin to or even below SD levels. A single injection of leptin in SD hamsters elevated SOCS3 mRNA to LD levels, whereas leptin treatment had no effect on SOCS3 gene expression in LD hamsters. Our results suggest that the development of leptin resistance in LD-acclimated hamsters involves SOCS3-mediated suppression of leptin signaling in the arcuate nucleus. Increased SOCS3 expression in LD hamsters is independent of body fat and serum leptin levels, suggesting that the photoperiod is able to trigger the biannual reversible switch in leptin sensitivity.


Novel chalcone and flavone derivatives as selective and dual inhibitors of the transport proteins ABCB1 and ABCG2.
During cancer chemotherapy, certain cancers may become cross-resistant to structurally diverse antineoplastic agents. This so-called multidrug resistance (MDR) is highly associated with the overexpression of ATP-binding cassette (ABC) transport proteins. These membrane-bound efflux pumps export a broad range of structurally diverse endo- and xenobiotics, including chemically unrelated anticancer agents. This translocation of drugs from the inside to the outside of cancer cells is mediated at the expense of ATP. In the last 40 years, three ABC transporters - ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP) - have mainly been attributed to the occurrence of MDR in cancer cells. One of the strategies to overcome MDR is to inhibit the efflux transporter function by small-molecule inhibitors. In this work, we investigated new chalcone- and flavone-based compounds for selective as well as broad-spectrum inhibition of the stated transport proteins. These include substituted chalcones with variations at rings A and B, and flavones with acetamido linker at position 3. The synthesized molecules were evaluated for their inhibitory potential against ABCB1, ABCC1, and ABCG2 in calcein AM and pheophorbide A assays. In further investigations with the most promising candidates from each class, we proved that ABCB1- and ABCG2-mediated MDR could be reversed by the compounds. Moreover, their intrinsic toxicity was found to be negligible in most cases. Altogether, our findings contribute to the understanding of ABC transport proteins and reveal new compounds for ongoing evaluation in the field of ABC transporter-mediated MDR.


Lipoid-cell variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of five cases.
Invasive urothelial carcinoma may present with many deceptive morphologic variants. We report the clinicopathologic and immunohistochemical features of 5 cases of the so-called lipid-cell variant of urothelial carcinoma. The tumors occurred in 4 men and 1 women aged from 56 to 80 years. Four cases were developed in the bladder and 1 case in the renal pelvis. All cases were revealed by a macroscopic hematuria. The tumors were composed of sheets and nests of large epithelial cells with an abundant clear multivacuolated cytoplasm mimicking lipoblasts. Nuclei were irregular, hyperchromatic, eccentric, and frequently indented by cytoplasmic vacuoles. Mucin stains (PAS, Alcian Blue) were negative. Tumor cells were strongly stained with cytokeratin 7, cytokeratin 20, and EMA but were negative with S-100 protein. In all cases, a usual high-grade urothelial carcinoma component was admixed with lipoid tumor cells. Two tumors infiltrated the bladder muscle, 2 cases invaded the bladder submucosa, and 1 case invaded the renal parenchyma. In the follow-up, despite appropriate surgical treatment, 4 patients died of the disease and 1 patient is alive without recurrence. Because of its rarity and the tumor cells' appearance, the lipoid-cell variant may be misdiagnosed and must be distinguished from liposarcoma or signet-ring cell carcinoma. In the present series, the lipoid-cell variant of urothelial carcinoma was associated with an aggressive behavior and a poor prognosis.