Hexabrix as a contrast agent for hysterosalpingography.
Hexabrix, a monoacidic dimeric iodinated contrast material, was compared with Renografin 60 (diatrizoate meglumine) for safety, tolerance, and efficacy in hysterosalpingography, in a double blind study of 52 patients. No serious adverse reactions were noted in either group of patients. Discomfort during and after the procedure was not statistically different in the two groups. No difference in radiographic quality was seen. It was concluded that Hexabrix, despite reduced osmolality and increased viscosity, offers no significant benefit over Renografin 60, but it is a safe and acceptable contrast agent for hysterosalpingography.


Associations of serum estradiol level, serum estrogen receptor-alpha level, and estrogen receptor-alpha polymorphism with male infertility: A retrospective study.
Estradiol regulates spermatogenesis partly via estrogen receptor-alpha (ESRα). This study aimed to analyze the associations of serum estradiol level, serum ESRα level, and ESRα gene polymorphisms with sperm quality.This retrospective study included infertile men attending the Reproductive Center, Affiliated Hospital of Youjiang Medical University for Nationalities, and a control group without a history of fertility (October, 2016 to March, 2017). Data regarding sperm quality, serum levels of estradiol and ESRα, and rs2234693C/T genotype were extracted from the medical records. Pearson/Spearman correlations (as appropriate) between estradiol level, ESRα level, and sperm quality parameters were evaluated.The analysis included 215 men with infertility and 83 healthy controls. The infertile group had higher serum levels of estradiol (147.57 ± 35.3 vs 129.62 ± 49.11 pg/mL, P < .05) and ESRα (3.02 ± 2.62 vs 1.33 ± 0.56 pg/mL, P < .05) than the control group. For the infertile group, serum estradiol level was negatively correlated with sperm concentration, percentage of progressively motile sperm, and percentage of sperm with normal morphology (r = 0.309, 0.211, and 0.246, respectively; all P < .05). Serum estradiol and ESRα levels were lower in infertile men with normozoospermia than in those with azoospermia, oligozoospermia, mild azoospermia, or malformed spermatozoa (all P < .05). Sperm concentration, percentage of progressively motile sperm, serum ESRα level, and serum estradiol level did not differ significantly among the rs2234693 CC, CT, and TT genotypes.Elevated serum levels of estradiol and possibly ESRα might have a negative impact on sperm quality and fertility, whereas single nucleotide polymorphisms at rs2234693 of the ESRα gene had little or no effect.


A Coupled Mathematical Model of Cell Migration, Vessel Cooption and Tumour Microenvironment during the Initiation of Micrometastases.
We propose a coupled mathematical model for the detailed quantitative analyses of initial microtumour and micrometastases formation by including cancer cell migration, host vessel cooption and changes in microenvironment. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. Migration probability of a migrating cell is assumed to be influenced by local chemical microenvironment. Pre-existing vessel cooption and remodelling are introduced according to the local haemodynamical microenvironment, such as interstitial pressure and vessel wall permeability. After the tumour cells and tumour vessels distribution are updated, the chemical substances are coupled calculated with the haemodynamical environment. The simulation results clearly reproduce the tumour cells migrate and proliferate along the pre-existing vessels at the very early stage of growth, which are consistent with many published experimental observations. In addition, the model demonstrates the interactions of tumour cells with the pre-existing vessels, which are believed to be essential for initial adhesion, proliferation, invasion, and micrometastases establishment. Quantitative analysis of tumour expansion in longitudinal and transverse directions shows that the cooption and migration along host vessels will be inhibited once angiogenesis phase occurs. The influences of the ability of cell migration and the inclusion of vessel cooption on the formation of micrometastases are discussed.


TiNbN Hard Coating Deposited at Varied Substrate Temperature by Cathodic Arc: Tribological Performance under Simulated Cutting Conditions.
This study focused on investigating the adhesion and tribological properties of niobium-doped titanium nitride (TiNbN) coatings deposited on D2 steel substrates at various substrate temperatures (Ts) under simulated cutting conditions. X-ray diffraction confirmed the presence of coatings with an FCC crystalline structure, where Nb substitutes Ti atoms in the TiN lattice. With increasing Ts, the lattice parameter decreased, and the crystallite material transitioned from flat-like to spherical shapes. Nanoindentation tests revealed an increase in hardness (H) with Ts, while a decrease in the elastic modulus (E) resulted in an improved elastic strain limit for failure (H/E) and plastic deformation resistance (H3/E2), thereby enhancing stiffness and contact elasticity. Adhesion analysis showed critical loads of ~50 N at Ts of 200 and 400 °C, and ~38 N at Ts of 600 °C. Cohesive failures were associated with lateral cracking, while adhesive failures were attributed to chipping spallation. The tribological behavior was evaluated using a pin-on-disk test, which indicated an increase in friction coefficients with Ts, although they remained lower than those of the substrate. Friction and wear were influenced by the surface morphology, facilitating the formation of abrasive particles. However, the absence of coating detachment in the wear tracks suggested that the films were capable of withstanding the load and wear.


Tiagabine-related non-convulsive status epilepticus in partial epilepsy: three case reports and a review of the literature.
There have been several recent reports of non-convulsive status epilepticus during tiagabine therapy in patients with partial epilepsy. We report three cases where elevation of tiagabine dosage was followed by electroclinical features, or electroencephalographic features without clinical signs, of non-convulsive status epilepticus. Administration of clonazepam and/or discontinuation to tiagabine lead to complete remission. In one case after re-exhibition of tiagabine the EEG again showed rhythmic delta waves. We review the other cases reported so far and discuss the different pathophysiological hypotheses about the association in the light of new experimental data.


Lactoferrin as an indicator of septicemia and endotoxemia in pigs.
The levels of plasma lactoferrin (LF) in response to endotoxin and Escherichia coli infusions in piglets were studied to obtain exact time relation of plasma LF increase in relation to start of endotoxin and E. coli infusions. A new enzyme-linked immunoassay of swine LF is presented. 13 piglets had a 10-fold rapid increase of plasma LF concentrations after 0.25 mg/kg endotoxin intravenous infusion. The initial rise was 3.4 mg/l/h. 14 piglets, receiving 1 x 10(11) E. coli intravenously, showed a higher increase of plasma LF concentrations, amounting to 6-9 mg/l/h. Thus, plasma LF was an early marker of septicemia and endotoxemia.


[Dr. Mihovil Milković--a provincial health correspondent and his inaugural dissertation in dentistry].
As capital of Dalmatia, Zadar also was a center of the province health organization. Headquarters of the provincial health correspondent, the most educated and respectable physician in the province, was situated in the town. His duty was to make all efforts for the health status of the population to improve and for the possible epidemics to prevent. Dr Mihovil Milković took over this duty for a certain period of time. At that time, Dalmatians mostly studied medicine in Padua, where Ph. D. in medicine could be obtained after having defended the inaugural dissertation. M. Milković obtained his Padua Ph. D. in 1847, having defended his dissertation in dentistry, entitled "A Brief Review of Pathology and Therapy of Dental Diseases". This dissertation is one of the oldest publications in the field of dentistry in our country, and by its originality and high quality it was on the same level with the medical science in Europe of that time.


Resveratrol improves the mitochondrial function and fertilization outcome of bovine oocytes.
The aim of the present study was to address the effect of resveratrol-mediated upregulation of sirtuin 1 (SIRT1) during oocyte maturation on mitochondrial function, the developmental ability of oocytes and on mechanisms responsible for blockage of polyspermic fertilization. Oocytes collected from slaughterhouse-derived ovaries were cultured in TCM-199 medium supplemented with 10% FCS and 0 or 20 µM resveratrol (Res). We examined the effect of Res on SIRT1 expression in in vitro-matured oocytes (Exp 1); fertilization and developmental ability (Exp 2); mitochondrial DNA copy number (Mt number), ATP content and mitochondrial membrane potential in matured oocytes (Exp 3); and the time required for proteinase to dissolve the zona pellucida following in vitro fertilization (as a marker of zona pellucida hardening), as well as on the distribution of cortical granules before and after fertilization (Exp 4). In Exp 1, the 20 µM Res treatment upregulated protein expression of SIRT1 in oocytes. In Exp 2, Res treatment improved the ratio of normal fertilization and the total cell number of blastocysts. In Exp 3, Res treatment significantly increased the ATP content in matured oocytes. Additionally, Res increased the overall Mt number and mitochondrial membrane potential, but the effect was donor-dependent. In Exp 4, Res-induced zona hardening improved the distribution and exocytosis of cortical granules after in vitro fertilization. In conclusion, Res improved the quality of oocytes by improving mitochondrial quantity and quality. In addition, Res added to the maturation medium enhanced SIRT1 protein expression in oocytes and improved fertilization via reinforcement of the mechanisms responsible for blockage of polyspermic fertilization.


Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68.
Murine gammaherpesvirus is a natural pathogen of wild rodents. In the laboratory it establishes an infection of epithelial cells and persists in B lymphocytes in a latent form. Inbred mice chronically infected with the virus develop a lymphoproliferative disease (LPD) similar to that seen in patients infected with Epstein-Barr virus. The frequency of LPD over a period of 3 years was 9% of all infected animals, with 50% of these displaying high grade lymphomas. The incidence of LPD was greatly increased when infected mice were treated with cyclosporin A. The majority of mice used in the experiments were BALB/c, although lymphomas were detected in mice on other genetic backgrounds, ie, CBA and B10Br. Lymphomas were associated with both lymphoid and nonlymphoid tissues (liver, lung, and kidney). In all cases of lymphomas studied thus far, there was a mixed B cell (B220+ve) and T cell (CD3+ve) phenotype. The B cells were light chain restricted, indicative of a clonal origin. Variable numbers of virus genome-positive cells were detected by in situ hybridization in and around the lymphomas. In contrast, no lytic antigen-positive cells were detected, indicating that genome-positive cells were either latently infected or undergoing an abortive infection. These observations suggest that murine gammaherpesvirus-infected mice may be an important model to study the pathogenesis of LPD associated with other gammaherpesviruses, such as Epstein-Barr virus.


Multiple acid-base and electrolyte disturbances upregulate NBCn1, NBCn2, IRBIT and L-IRBIT in the mTAL.
The roles of the Na+ /HCO3- cotransporters NBCn1 and NBCn2 as well as their activators IRBIT and L-IRBIT in the regulation of the mTAL transport of NH4+ , HCO3- , and NaCl are investigated. Dietary challenges of NH4 Cl, NaHCO3 or NaCl all increase the abundance of NBCn1 and NBCn2 in the outer medulla. The three challenges generally produce parallel increases in the abundance of IRBIT and L-IRBIT in the outer medulla. Both IRBIT and L-IRBIT powerfully stimulate the activities of the mTAL isoforms of NBCn1 and NBCn2 as expressed in Xenopus oocytes. Our findings support the hypothesis that NBCn1, NBCn2, IRBIT and L-IRBIT appropriately promote NH4+ shunting but oppose HCO3- and NaCl reabsorption in the mTAL, and thus are at the nexus of the regulation pathways for multiple renal transport processes. The medullary thick ascending limb (mTAL) plays a key role in urinary acid and NaCl excretion. NBCn1 and NBCn2 are present in the basolateral mTAL, where NBCn1 promotes NH4+ shunting. IRBIT and L-IRBIT (the IRBITs) are two powerful activators of certain acid-base transporters. Here we use western blotting and immunofluorescence to examine the effects of multiple acid-base and electrolyte disturbances on expression of NBCn1, NBCn2 and the IRBITs in rat kidney. We also use electrophysiology to examine the functional effects of IRBITs on NBCn1 and NBCn2 in Xenopus oocytes. NH4 Cl-induced metabolic acidosis (MAc) substantially increases protein expression of NBCn1 and NBCn2 in the outer medulla (OM) of rat kidney. Surprisingly, NaHCO3 -induced metabolic alkalosis (MAlk) and high-salt diet (HSD) also increase expression of NBCn1 and NBCn2 (effect of NaHCO3 > HSD). Moreover, all three challenges generally increase OM expression of the IRBITs. In Xenopus oocytes, the IRBITs substantially increase the activities of NBCn1 and NBCn2. We propose that upregulation of basolateral NBCn1 and NBCn2 plus the IRBITs in the mTAL: (1) promotes NH4+ shunting by increasing basolateral HCO3- uptake to neutralize apical NH4+ uptake during MAc; (2) inhibits HCO3- reabsorption during MAlk by opposing HCO3- efflux via the basolateral anion exchanger AE2; and (3) inhibits NaCl reabsorption by mediating (with AE2) net NaCl backflux into the mTAL cell during HSD. Thus, NBCn1, NBCn2 and the IRBITs are at the nexus of the regulatory pathways for multiple renal transport processes.


A manual small molecule screen approaching high-throughput using zebrafish embryos.
Zebrafish have become a widely used model organism to investigate the mechanisms that underlie developmental biology and to study human disease pathology due to their considerable degree of genetic conservation with humans. Chemical genetics entails testing the effect that small molecules have on a biological process and is becoming a popular translational research method to identify therapeutic compounds. Zebrafish are specifically appealing to use for chemical genetics because of their ability to produce large clutches of transparent embryos, which are externally fertilized. Furthermore, zebrafish embryos can be easily drug treated by the simple addition of a compound to the embryo media. Using whole-mount in situ hybridization (WISH), mRNA expression can be clearly visualized within zebrafish embryos. Together, using chemical genetics and WISH, the zebrafish becomes a potent whole organism context in which to determine the cellular and physiological effects of small molecules. Innovative advances have been made in technologies that utilize machine-based screening procedures, however for many labs such options are not accessible or remain cost-prohibitive. The protocol described here explains how to execute a manual high-throughput chemical genetic screen that requires basic resources and can be accomplished by a single individual or small team in an efficient period of time. Thus, this protocol provides a feasible strategy that can be implemented by research groups to perform chemical genetics in zebrafish, which can be useful for gaining fundamental insights into developmental processes, disease mechanisms, and to identify novel compounds and signaling pathways that have medically relevant applications.


Directly reprogramming fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by defined factors.
The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types represents a great potential technology for regenerative medicine. In the present study, the potential of key developmental adipogenic, neurogenic and hepatogenic regulators to reprogram human fibroblasts into adipocytes, neurocytes and hepatocytes was investigated. The results demonstrated that direct reprogramming of octamer-binding transcription factor 4 (Oct4) and CCAAT-enhancer-binding protein (C/EBP)β activated C/EBPα and peroxisome proliferator-activated receptor-γ expression, inducing the conversion of fibroblasts into adipocytes. Similarly, direct reprogramming of the transcription factors sex determining region-box 2, trans-acting T-cell specific transcription factor (GATA-3) and neurogenic differentiation 1 in fibroblasts may induce neurogenic differentiation through hemagglutinating virus of Japan envelope (HVJ-E) transfection. Moreover, hepatogenic differentiation was induced by combining the direct reprogramming of Oct4, GATA-3, hepatocyte nuclear factor 1 homeobox α and forkhead box protein A2 in fibroblasts. These results demonstrate that specific transcription factors and reprogramming factors are able to directly reprogram fibroblasts into adipogenic, neurogenic and hepatogenic differentiation lineages by HVJ-E transfection.


Surgical site infection and validity of staged surgical procedure in emergent/urgent surgery for ulcerative colitis.
Although restorative proctocolectomy is recognized as a standard procedure for ulcerative colitis, infectious complications after surgery cannot be disregarded. The aim of this study was to define predictors of surgical site infection (SSI) in urgent/emergent surgery for ulcerative colitis. We performed prospective SSI surveillance for 90 consecutive patients. Possible risk factors were analyzed by logistic regression analyses. Incidences of incisional SSI (i-SSI) and organ/space SSI were 31.1% and 6.9%, respectively, and increased significantly with higher wound class (P < 0.01). Multivariate analysis showed wound class ≥3 as an independent risk factor for i-SSI. In univariate analysis, although the mucous fistula procedure was a risk factor for i-SSI (odds ratio, 3.45; P < 0.01), Hartmann procedure also represented a risk factor for o-SSI (odds ratio, 12.8; P < 0.01). Urgent restorative proctocolectomy for patients without high wound class and emergent total colectomy with mucous fistula for patients with high wound class appear to represent feasible options.


Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway.
The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 μM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5-2 μM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway.


Effect of the PTHrP(1-34) analog abaloparatide on inducing chondrogenesis involves inhibition of intracellular reactive oxygen species production.
Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of articular cartilage. Mesenchymal stem cells transplanted to damaged tissues are promising for OA cartilage repair. However, these cells are poor survival after transplantation and acquire hypertrophic properties during chondrogenic induction. Parathyroid hormone-related protein (PTHrP) promotes chondrogenesis and suppresses chondrocyte hypertrophic differentiation. Additionally, PTHrP was reported to have anti-oxidant effects. The synthetic PTHrP(1-34) analog abaloparatide (ABL) is a newly approved drug for osteoporosis therapy. It is unknown whether ABL stimulates chondrogenesis and affects intracellular reactive oxygen species (ROS) production. By using mouse embryonic limb bud mesenchymal stem cells in micromass culture as an in vitro model of chondrogenic differentiation, we found that mesenchymal stem cells in micromass cultures spontaneously produced ROS, and N-acetyl-l-cysteine, a potent antioxidant, enhanced chondrogenesis. The effect of ABL on stimulation of chondrogenesis is involved in its inhibition of intracellular ROS generation. These novel findings support the use of ABL for the damaged cartilage regeneration.


Photophysics of the platinum(II) terpyridyl terpyridylacetylide platform and the influence of Fe(II) and Zn(II) coordination.
The synthesis, structural characterization, and photoluminescence (PL) properties of the square-planar terpyridylplatinum(II) complex [ ( t )Bu 3tpyPtCCtpy] (+) ( 1) and the octahedral trinuclear Fe (II) and Zn (II) analogues [Fe( ( t )Bu 3tpyPtCCtpy) 2] (4+) ( 2) and [Zn( ( t )Bu 3tpyPtCCtpy) 2] (4+) ( 3) are described. The photophysical properties of the mononuclear Pt (II) complex 1 are consistent with a charge-transfer excited-state parentage producing a large Stokes shift with a concomitant broad, structureless emission profile. The Fe-based ligand-field states in 2 provide an efficient nonradiative deactivation pathway for excited-state decay, resulting in a nonemissive compound at room temperature. Interestingly, upon chelation of 1 with Zn (II), a higher energy charge-transfer emission with a low-energy shoulder and a 215 ns excited-state lifetime is produced in 3. A spectroscopically identical species relative to 3 was produced in control experiments when 1 was reacted with excess protons (HClO 4) as ascertained by UV-vis and static PL spectra measured at room temperature and 77 K. Therefore, the chelation of Zn (II) to 1 is acid-base in nature, and its Lewis acidity renders the highest occupied molecular orbital level in 1 much less electron-rich, which induces a blue shift in both the absorption and emission spectra. At 77 K, complexes 1, 3, and protonated 1 display at least one prevalent vibronic component in the emission profile (1360 cm (-1)) resembling PL emanating from a ligand-localized excited-state, indicating that these emitting states are inverted relative to room temperature. These results are qualitatively confirmed by the application of time-dependent theory using only the 1360 cm (-1) mode to reproduce the low-temperature emission spectra.


Liver- and placenta-like alkaline phosphatases (EC 22.214.171.124) isoenzymes in normal human neutrophils.
Alkaline phosphatase (AP) has been characterized in the neutrophil polymorphonuclear leukocytes (PMN) from 14 healthy adults. The biochemical properties of the isoenzymes were analyzed by the following methods: enzyme assays, slab gel electrophoresis, thermostability, inhibition pattern using four chemical inhibitors, and immunological specificity. In normal PMNs, two types of AP have been found: a thermolabile isoenzyme identical to the liver/bone/kidney type and a thermostable isoenzyme with respect to its electrophoretic properties, its level of thermostability, its immunological specificity, the thermostable isoenzyme resembles the placental form more closely than the intestinal form. These results are consistent with the proposal that granulocyte AP is a heterogeneous enzyme. Two enzyme forms appear to be expressed in this blood cell.


Dopaminergic modulation and rod contribution in the generation of oscillatory potentials in the tiger salamander retina.
The roles of rod and cone input and of dopamine in the generation of oscillatory potentials were studied in tiger salamander retina. Under scotopic conditions, oscillations were elicited with a green, but not a red stimulus. With mesopic background illumination, both stimuli caused oscillations. Addition of quinpirole to a mesopic retina eliminated oscillations while SKF-38393 had no effect. Similarly, addition of sulpiride to a light-adapted retina elicited oscillatory activity, but SCH 22390 had no effect. These results suggest that oscillatory potentials are elicited through activation of the rod pathway and are modulated by dopamine through D2-receptors.


Within arm's reach: The role of proximity in speech generating device use of ambulatory children with autism.
Purpose: Augmentative and Alternative Communication (AAC) provides an alternative means of communication for individuals who are unable to effectively communicate using spoken language. The present study seeks to investigate the role of proximity in facilitating AAC (specifically Speech Generating Devices; SGD) use in a homogeneous population: ambulatory school-aged children with autism spectrum disorder (ASD).Method: Twelve school-age children with ASD who use an SGD as their primary mode of communication participated in the study. The percentage of time the child was within the proximity of their device was calculated over nine videotaped sessions and data logging provided information regarding device use over an 18-week period.Result: Children were in proximity to their device 65% of the time. There was a significant positive correlation between percentage of time in proximity to device and the average minutes of device use on the day video recorded. Exploratory analyses revealed that communicative abilities may be more connected to proximity than school context.Conclusion: These results support the importance of developing a program for assuring device proximity in order to encourage consistent device use in minimally verbal ambulatory school-age children with ASD.


Building a regional health equity movement: the grantmaking model of a local health department.
The Boston Public Health Commission's Center for Health Equity and Social Justice provides grant funding, training, and technical assistance to 15 organizations and coalitions across New England to develop, implement, and evaluate community-based policy and systems change strategies that address social determinants of health and reduce racial and ethnic health inequities. This article describes Boston Public Health Commission's health equity framework, theory of change regarding the elimination of racial and ethnic health inequities, and current grantmaking model. To conclude, the authors evaluate the grant model and offer lessons learned from providing multiyear regional grants to promote health equity.


Assessing the quality of democratic deliberation: a case study of public deliberation on the ethics of surrogate consent for research.
"Deliberative democracy" is an increasingly popular method for soliciting public input on health care policies. There are a number of ways of organizing deliberative democracy (DD) sessions, but they generally involve gathering a group of citizens, supplying them with information relevant to the policy in question, giving them time to interact with each other and with experts in the policy area, and collecting their informed and considered opinions. As the method has become more widely used, some have questioned the quality of the public input it generates. Although theorists of DD agree that "good" input - i.e., input that is the product of careful and thorough reflection - is an essential aspect of useful and effective deliberation, few have actually measured the quality of deliberative sessions. As part of a DD project organized to help guide policies on the morally complex question of allowing surrogate permission to enroll persons with dementia in medical research, we developed and tested measures of "quality of deliberation." After a brief discussion of the substantive results of our research - survey data from participants in the DD sessions and control groups showed a significant change in participants' attitudes toward surrogate consent - we examine the process by which this change occurred, describing and assessing the characteristics of our DD sessions. We use both quantitative and qualitative data from our DD sessions, conducted in southeastern Michigan, United States, to examine four dimensions of the quality of deliberation: 1) equal participation by all members of the session, 2) respect for the opinions of others, 3) a willingness to adopt a societal perspective on the issue in question (rather than a focus on what is best for participants as individuals), and 4) reasoned justification of one's positions. We demonstrate that DD can be reliably used to elicit opinions of the public and show how analysis of the quality of deliberations can offer insight into the ways opinions about ethical dilemmas are formed and changed.


Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer.
The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, Interferon (IFN)-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors. Ligand-independent regulation of ISGs was also observed, as basal transcript levels were markedly higher in cells with PR knockdown. PR repressed ISG transcription in response to IFN treatment, the canonical mechanism through which these genes are activated. Liganded PR is robustly recruited to enhancer regions of ISGs, and ISG transcriptional repression is dependent upon PR's ability to bind DNA. In response to PR activation, key regulatory transcription factors that are required for IFN-activated ISG transcription, STAT2 and IRF9, exhibit impaired recruitment to ISG promoter regions, correlating with PR/ligand-dependent ISG transcriptional repression. IFN activation is a critical early step in nascent tumor recognition and destruction through immunosurveillance. As the large majority of breast tumors are PR positive at the time of diagnosis, PR-dependent downregulation of IFN signaling may be a mechanism through which early PR-positive breast tumors evade the immune system and develop into clinically relevant tumors.Implications: This study highlights a novel transcriptional mechanism through which PR drives breast cancer development and potentially evades the immune system. Mol Cancer Res; 15(10); 1331-40. ©2017 AACR.


Area postrema and alcohol: effects of area postrema lesions on ethanol self-administration, pharmacokinetics, and ethanol-induced conditioned taste aversion.
An investigation was carried out to test the hypothesis that the area postrema (AP) may detect ethanol as a blood-borne toxin and thereby mediate aversive postingestinal effects of the drug. These aversive effects in turn may impose an upper limit on the amount of drug that can be consumed. In Experiment 1 rats had continuous access to water and a 4% ethanol solution. Animals with AP lesions drank more ethanol than sham-operated controls. No differences in drug disposition or metabolism were found when these rats were injected with ethanol and blood ethanol levels were measured. If the AP lesions resulted in increased ethanol drinking because of a reduction in the aversive effects of the drug, then the lesions might also be expected to attenuate a conditioned taste aversion induced by ethanol. In Experiment 2, groups of lesioned and sham-operated rats drank a novel tasting fluid and then were given i.p. injections of ethanol (0.9, 1.2, or 1.6 g/kg) or vehicle. Similar degrees of aversion to the taste of the fluid developed in both the lesioned and the sham-control groups. Since the AP lesion did not result in the attenuation of the ethanol-induced conditioned taste aversion, it was suggested that the AP may not mediate the aversive consequences of ethanol and that the increased ethanol self-administration observed in Experiment 1 may be due to other effects of the lesion.


Characterization of a spray-dried candidate HPV L2-VLP vaccine stored for multiple years at room temperature.
HPV infections are associated with human cancers. Although three prophylactic vaccines have been approved to protect against HPV infections, the vaccines require cold-chain storage and may not be suitable for third world countries with less developed refrigeration facilities. We previously developed a bacteriophage L2 virus-like particle (VLP)-based candidate vaccine, which elicited broadly protective antibodies against diverse HPV types. Spray-drying of MS2-16L2 VLPs into a dry powder enhanced the stability of these VLPs. Building on these studies, we assessed the long-term stability and immunogenicity of the spray-dried VLPs. Mice immunized with a single dose of spray-dried MS2-16L2 VLPs, which had been stored for 14 months at room temperature (RT), were partially protected from challenge with a high dose of HPV16, one year after immunization. However, immunization with two doses of MS2-16L2 VLPs stored at RT for 34 months elicited high titer anti-HPV antibodies. More importantly, this group of mice showed significant protection from HPV16, 4 months after immunization. These results suggest that spray-dried MS2-16L2 VLPs retain their effectiveness after long-term storage at RT, and may be suitable in third world countries with less developed refrigeration facilities.


Surelease as granulating liquid in preparation of sustained release matrices of ethylcellulose and theophylline.
Use of Surelease as a granulation liquid in preparation of granules and matrices of theophylline and ethylcellulose was evaluated. Physical mixtures (at 1:1 or 1:1.5 drug:polymer) were granulated using water, Surelease or diluted Surelease as granulating liquid. The granule characteristics (shape, size, flow rate, mechanical properties, friability and release profile) were studied. Afterwards, matrices were manufactured and their crushing strengths, friability and release profiles were determined. Granulation produced agglomerated particles with better flowability than physical mixtures. Change of granulation liquid from water to Surelease or diluted Surelease led to the marginal increase in size of granules at 1:1 drug:polymer, however, the flow rate and Carr's index were considerably improved. The hardness, elastic modulus, friability and rate of drug release were not affected by granulation liquid. Increase in polymer content resulted in reduction in size of granules, flow rate, elastic modulus and rate of drug release. However hardness of the granules was unaffected. Granulation process and granulation liquid did not affect the hardness, and dissolution rate of matrices at 1:1 drug:polymer, while the use of Surelease or diluted Surelease as a granulating liquid, increased the hardness and decreased drug release rate at 1:1.5 drug:polymer. Matrices prepared from Surelease or diluted Surelease showed similar characteristics. Surelease is a suitable granulating liquid for preparation of ethylcellulose matrices especially when high amount of polymer is used and could not only improve the flow and compatibility of the granules, but also help in reducing the rate of drug release.


A new condensable composite for the restoration of posterior teeth.
Undoubtedly the greatest resistance of clinicians to use composite resins in posterior teeth relates to technique sensitivity, time consumption, and complexity. Placing conventional posterior composite resins does not take into account that composites differ considerably from amalgam. This is particularly true with respect to its physical characteristics, especially insertion and packing properties. The development of a posterior composite resin that can be placed by an amalgam carrier and subsequently packed or condensed as an amalgam, should assist clinicians greatly in their ability to successfully restore class II cavity preparations. Acknowledgment is expressed to Bruce Small, DMD, for the clinical dentistry and slides.


A comparison of interalar width and intercanine distance in Malay males and females.
The interalar width of the nose and the intercanine distance were measured in 266 Malay subjects (111 males and 155 females) randomly selected from the students of the School of Medical Sciences. University Sains Malaysia in Kota Bharu, Malaysia. The mean interalar width of the nose in male subjects was 39.8 +/- 2.3 mm (range 34-45 mm) and in female subjects 36.2 mm +/- 2.2 mm (range 30-41 mm). There is a statistically significant difference (t = 12.9: p < 0.05) in the nasal width between male and female Malay subjects. This agrees with the findings of other similar studies that males have wider noses than females. The mean maxillary intercanine distance in male subjects was 36.7 = 2.6 mm (range 30-42 mm) and in female subjects 36.2 = 2.3 mm (range 30-42 mm). The anterior maxillary arch is significantly wider in Malay subjects compared to Chinese from Singapore (Keng 1986) as p < 0.05 and to Caucasians (Sawiris 1977) as p < 0.05. There is a significant correlation (r = 0.312; p < 0.05) between the nasal width and the intercanine distance in female subjects but not in male subjects.


Photoabsorption and photofragmentation of isolated cationic silver cluster-tryptophan hybrid systems.
We present a theoretical study of the size and structure selective absorption properties of cationic silver cluster-tryptophan Trp-Ag(n)(+) (n = 2-5,9) hybrid systems supported by photofragmentation experiments. Our time-dependent density functional theory calculations provide insight into the nature of excitations in interacting nanoparticle-biomolecule subunits and allow to determine characteristic spectral features as fingerprints of two different classes of structures: charge solvated and zwitterionic. Moreover, different types of charge transfer transitions have been identified. Charge transfer from pi system of tryptophan to silver cluster occurs for charge solvated structures while charge transfer from silver to the NH(3) (+) group takes place for zwitterionic structures. This has been confirmed by experimentally measured photofragmentation channels and molecular dynamics simulations. Our findings provide fundamental insight into the structure- and size-dependent mechanism responsible for the enhanced absorption and emission in nanoparticle-biomolecular hybrid systems.


Identification of monoclonal antibodies that recognize novel epitopes in native chondroitin/dermatan sulfate glycosaminoglycan chains: their use in mapping functionally distinct domains of human skin.
Five monoclonal antibodies (MAb), 7D4, 4C3, 6C3, 4D3, and 3C5, were produced in mice immunized with high buoyant density embryonic chick bone marrow proteoglycans (PGs) as antigen. All of these MAb recognized epitopes in native chick bone marrow and cartilage PGs which could be selectively removed by chondroitinase ABC and chondroitinase AC II, indicating that their epitopes were present in chondroitin sulfate glycosaminoglycans (GAGs). These MAb recognized epitopes present in purified cartilage PGs obtained from a wide variety of different vertebrate species. However, none of the new MAb detected epitopes in Swarm rat chondrosarcoma PG. On the basis of these results, we propose that these MAb recognize novel epitopes located in chondroitin sulfate/dermatan sulfate glycosaminoglycan (CS/DS GAG) chains, representing at least four and possibly five different structures. Immunocytochemical studies have shown that the epitopes identified by these new MAb are differentially distributed in tissues. All of these MAb immunocytochemically detected epitopes in embryonic chick cartilage and bone marrow. Three of them (4C3, 7D4, and 6C3) recognized epitopes in adult human skin. All three detected epitopes in the epidermis, one (6C3) strongly detected epitopes in the papillary dermis, and two (4C3, 7D4) detected epitopes in the reticular dermis. Immunostaining patterns in skin using the new MAb directed against native CS/DS structures were distinctly different from those obtained using MAb against the common CS isomers. The distribution of these CS epitopes in functionally distinct domains of different tissues implies that these structures have functional and biological significance.


Volumetric interpretation of protein adsorption: competition from mixtures and the Vroman effect.
A Vroman-like exchange of different proteins adsorbing from a concentrated mixture to the same hydrophobic adsorbent surface is shown to arise naturally from the selective pressure imposed by a fixed interfacial-concentration capacity (w/v, mg/mL) for which protein molecules compete. A size (molecular weight, MW) discrimination results because fewer large proteins are required to accumulate an interfacial w/v concentration equal to smaller proteins. Hence, the surface region becomes dominated by smaller proteins on a number-or-mole basis through a purely physical process that is essentially unrelated to protein biochemistry. Under certain conditions, this size discrimination can be amplified by the natural variation in protein-adsorption avidity (quantified by partition coefficients P) because smaller proteins (MW<50 kDa) have been found to exhibit characteristically higher P than larger proteins (MW<50 kDa). The standard depletion method is implemented to measure protein-adsorption competition between two different test proteins (i and j) for the same hydrophobic octyl sepharose adsorbent particles. SDS-gel electrophoresis is used as a multiplexing, separation-and-quantification tool for this purpose. Identical results obtained using sequential and simultaneous competition of human immunoglobulin G (IgG, protein j) with human serum albumin (HSA, protein i) demonstrates that HSA was not irreversibly adsorbed to octyl sepharose over a broad range of competing solution concentrations. A clearly observed exchange of HSA for IgG or fibrinogen (Fib) shows that adsorption of different proteins (i competing with j) to the same hydrophobic surface is coupled whereas adsorption among identical proteins (i or j adsorbing from purified solution) is not coupled. Interpretive theory shows that this adsorption coupling is due to competition for the fixed surface capacity. Theory is extended to hypothetical ternary mixtures using a computational experiment that illustrates the profound impact size-discrimination has on adsorption from complex mixtures such as blood.


Phase transitions in traffic flow on multilane roads.
Based on empirical and numerical analyses of vehicular traffic, the physics of spatiotemporal phase transitions in traffic flow on multilane roads is revealed. The complex dynamics of moving jams observed in single vehicle data measured by video cameras on American highways is explained by the nucleation-interruption effect in synchronized flow, i.e., the spontaneous nucleation of a narrow moving jam with the subsequent jam dissolution. We find that (i) lane changing, vehicle merging from on-ramps, and vehicle leaving to off-ramps result in different traffic phases-free flow, synchronized flow, and wide moving jams-occurring and coexisting in different road lanes as well as in diverse phase transitions between the traffic phases; (ii) in synchronized flow, the phase transitions are responsible for a non-regular moving jam dynamics that explains measured single vehicle data: moving jams emerge and dissolve randomly at various road locations in different lanes; (iii) the phase transitions result also in diverse expanded general congested patterns occurring at closely located bottlenecks.


Sodium lauryl ether sulfate (SLES) degradation by nitrate-reducing bacteria.
The surfactant sodium lauryl ether sulfate (SLES) is widely used in the composition of detergents and frequently ends up in wastewater treatment plants (WWTPs). While aerobic SLES degradation is well studied, little is known about the fate of this compound in anoxic environments, such as denitrification tanks of WWTPs, nor about the bacteria involved in the anoxic biodegradation. Here, we used SLES as sole carbon and energy source, at concentrations ranging from 50 to 1000 mg L-1, to enrich and isolate nitrate-reducing bacteria from activated sludge of a WWTP with the anaerobic-anoxic-oxic (A2/O) concept. In the 50 mg L-1 enrichment, Comamonas (50%), Pseudomonas (24%), and Alicycliphilus (12%) were present at higher relative abundance, while Pseudomonas (53%) became dominant in the 1000 mg L-1 enrichment. Aeromonas hydrophila strain S7, Pseudomonas stutzeri strain S8, and Pseudomonas nitroreducens strain S11 were isolated from the enriched cultures. Under denitrifying conditions, strains S8 and S11 degraded 500 mg L-1 SLES in less than 1 day, while strain S7 required more than 6 days. Strains S8 and S11 also showed a remarkable resistance to SLES, being able to grow and reduce nitrate with SLES concentrations up to 40 g L-1. Strain S11 turned out to be the best anoxic SLES degrader, degrading up to 41% of 500 mg L-1. The comparison between SLES anoxic and oxic degradation by strain S11 revealed differences in SLES cleavage, degradation, and sulfate accumulation; both ester and ether cleavage were probably employed in SLES anoxic degradation by strain S11.


High-throughput sample handling and data collection at synchrotrons: embedding the ESRF into the high-throughput gene-to-structure pipeline.
An automatic data-collection system has been implemented and installed on seven insertion-device beamlines and a bending-magnet beamline at the ESRF (European Synchrotron Radiation Facility) as part of the SPINE (Structural Proteomics In Europe) development of an automated structure-determination pipeline. The system allows remote interaction with beamline-control systems and automatic sample mounting, alignment, characterization, data collection and processing. Reports of all actions taken are available for inspection via database modules and web services.


Increased visual and cognitive demands emphasize the importance of meeting visual needs at all distances while driving.
Having an optimal quality of vision as well as adequate cognitive capacities is known to be essential for driving safety. However, the interaction between vision and cognitive mechanisms while driving remains unclear. We hypothesized that, in a context of high cognitive load, reduced visual acuity would have a negative impact on driving behavior, even when the acuity corresponds to the legal threshold for obtaining a driving license in Canada, and that the impact observed on driving performance would be greater with the increase in the threshold of degradation of visual acuity. In order to investigate this relationship, we examined driving behavior in a driving simulator under optimal and reduced vision conditions through two scenarios involving different levels of cognitive demand. These were: 1. a simple rural driving scenario with some pre-programmed events and 2. a highway driving scenario accompanied by a concurrent task involving the use of a navigation device. Two groups of visual quality degradation (lower/ higher) were evaluated according to their driving behavior. The results support the hypothesis: A dual task effect was indeed observed provoking less stable driving behavior, but in addition to this, by statistically controlling the impact of cognitive load, the effect of visual load emerged in this dual task context. These results support the idea that visual quality degradation impacts driving behavior when combined with a high mental workload driving environment while specifying that this impact is not present in the context of low cognitive load driving condition.


Enhancing intestinal barrier efficiency: A novel metabolic diseases therapy.
Physiologically, the intestinal barrier plays a crucial role in homeostasis and nutrient absorption and prevents pathogenic entry, harmful metabolites, and endotoxin absorption. Recent advances have highlighted the association between severely damaged intestinal barriers and diabetes, obesity, fatty liver, and cardiovascular diseases. Evidence indicates that an abated intestinal barrier leads to endotoxemia associated with systemic inflammation, insulin resistance, diabetes, and lipid accumulation, accelerating obesity and fatty liver diseases. Nonetheless, the specific mechanism of intestinal barrier damage and the effective improvement of the intestinal barrier remain to be explored. Here, we discuss the crosstalk between changes in the intestinal barrier and metabolic disease. This paper also highlights how to improve the gut barrier from the perspective of natural medicine, gut microbiota remodeling, lifestyle interventions, and bariatric surgery. Finally, potential challenges and prospects for the regulation of the gut barrier-metabolic disease axis are discussed, which may provide theoretical guidance for the treatment of metabolic diseases.


Intraventricular administration of nerve growth factor induces ornithine decarboxylase in peripheral tissues of the rat.
Intraventricular administration of nerve growth factor causes an increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 18.104.22.168) in liver, kidney, and adrenal as well as in brain itself. An increase in the concentration of corticosterone in the blood was also observed. Adrenalectomy, hypophysectomy, or pituitary stalk section inhibits the increase of ornithine decarboxylase activity in the peripheral tissues. Ornithine decarboxylase activity in the brain, however, responds to nerve growth factor in these animals. The data indicate that nerve growth factor causes an acitivation of the hypothalamo-hypophyseal endocrine system.


Enhancing forecast accuracy using combination methods for the hierarchical time series approach.
This study aims to investigate whether combining forecasts generated from different models can improve forecast accuracy rather than individual models using the hierarchical time series. Various approaches of hierarchical forecasting have been considered; a bottom-up, top-down, and an optimal combination approach. Autoregressive moving averages (ARIMA) and exponential smoothing (ETS) were used as forecasting models in creating forecasting for all levels in the hierarchy to show the effect of different forecasting methods for each hierarchical model. The results indicated that the Minimum Trace Sample estimator (MinT-Sample) and the bottom-up approaches with the ARIMA model have good predictive performance than other approaches. Moreover, the forecasts from the MinT-Sample and bottom-up approaches were combined using five different combining methods. The experimental results showed that the (AC) method is superior to all other combining methods and more accurate than other individual models at level zero (international total trade in Egypt) and level one (total exports, and total imports). So, combining forecasts generated from different models by hierarchical time series leads to more accurate forecasting of the value of imports and exports which will improve the overall international trade performance, and that is through using the forecasting values of imports and exports to plan for improving the trade balance and drawing up a more efficient production policy. Finally, the study recommends using hierarchical forecasting methods in the areas of international trade, and the Ministry of Commerce and Industry could adopt the results of this study to produce precise forecasts for international trade. Moreover, the results of this study are to be a guide for the researchers to apply these approaches in other fields to improve the performance of forecasting.


Bilateral juvenile granulosa cell tumors in a 4-month-old dysmorphic infant. A clinical, histologic, and ultrastructural study.
Juvenile granulosa cell tumors were encountered within bilateral cystic ovarian masses in a 4-month-old infant. The child was the product of a consanguinous pregnancy, and manifested poor growth, relative microcephaly, facial asymmetry, and a malformed left ear. There was no history of gestational drug or hormone ingestion, and no evidence of abnormal endocrine activity after birth, however, the serum alpha-fetoprotein level was mildly elevated. The tumors were well defined by sonography and there was no evidence of metastasis. Histologically, a dense proliferation of round to oval tumor cells showed considerable individual cell necrosis and frequent microcyst formation. There was no evidence of luteinization and only mild nuclear pleomorphism. Immunoperoxidase study failed to reveal alpha-fetoprotein. Ultrastructural study supported the granulosa cell nature of the tumor, but a few cells contained bundles of intracytoplasmic filaments. There has been no evidence of recurrent disease during a 16-month follow-up period, and serial alpha-fetoprotein determinations have remained in the reference range. Comparison with two previously reported bilateral juvenile granulosa cell tumors suggests that this tumor occurs in young infants, and is amenable to conservative therapy.


[Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].
The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA. GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.


Lutembacher syndrome variant: Rheumatic heart disease involving all four valves and associated with an atrial septal defect in a child.
Rheumatic heart disease (RHD) is the most common cause of acquired heart disease in children and young adults in developing countries. It results from throat infection with group A beta hemolytic streptococcus that proceeds to acute rheumatic fever (ARF). We report a 13 years old girl from Darfur presenting with recurrent acute rheumatic fever for 4 years that led to affection of all her heart valves with severe mitral and tricuspid regurgitation together with moderate pulmonary and mild aortic valve regurgitation. There was an associated atrial septal defect (Lutembacher syndrome variant). The disease was severe and led to cardiogenic shock and death while awaiting surgery. The case highlights the impact of RHD on young people and the need to implement control programs for RHD in Sudan.


Immunoglobulins in periodontal tissues. II. Concentrations of immunoglobulins in granulation tissue from pockets of periodontosis and periodontitis patients.
In recent years evidence in the literature has indicated that the immune response may play an important role in the initiation and progression of the periodontal diseases. A study was initiated to determine the IgA, IgG, and IgM concentrations in the granulation tissue removed from deep infrabony pockets of patients with periodontosis and advanced periodontitis. Comparison of mean immunoglobulin levels between the periodontosis and periodontitis groups revealed a statistically significant increase (P less than 0.05) for IgG in the granulation tissue from the periodontosis group. The possible implications of these findings are discussed.


The impact of obesity on psychological well-being.
Children and adolescents with obesity face stigmatization and discrimination in many areas of their lives, and it has been assumed that their psychological well-being will be compromised as a result. This chapter examines the most recent empirical evidence on the relationship between childhood obesity and body dissatisfaction, self-esteem and depression. Studies of clinical samples typically report poorer psychological well-being in treatment seekers when compared with population-based obese and normal weight controls. However, research in community samples suggests that despite moderate levels of body dissatisfaction, few obese children are depressed or have low self-esteem. A number of important moderators and mediators of the association between obesity and well-being have emerged, with females, Caucasians and adolescents being particularly at risk. Implications for treatment and future research priorities are suggested.


The protective effect of infliximab against carbon tetrachloride-induced acute lung injury.
Carbon tetrachloride (CCl4) causes pulmonary toxicity. Infliximab (Ib) is a potent inhibitor of tumor necrosis factor-alpha (TNF-α). We aimed to investigate whether Ib has a protective effect on CCl4 induced lung injury. Rats were divided into control, CCl4, and CCl4+Ib groups. A single dose of 2 ml/kg CCI4 was administered to CCI4 group and a single dose of 7 mg/kg Ib was given to CCl4+Ib group 24 hr before applying CCI4. TNF-α, malondialdehyde (MDA), nitric oxide (NO) and caspase-3 levels of the CCl4 group were markedly higher than both the control and CCl4+Ib groups. The CCI4+Ib group had lower histopathological injury than the CCl4 group. Ib as a strong TNF-α blocker decreases the production of proinflammatory cytokines, MDA, and oxidative stress leading to a protective effect against CCl4 induced lung tissue injury.


MicroRNA-1277 Inhibits Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells by Targeting and Suppressing BMP4 Expression and Reflects the Significant Indicative Role in Hepatocellular Carcinoma Pathology and Diagnosis After Magnetic Resonance Imaging Assessment.
Our study aimed to investigate the roles and possible regulatory mechanism of miR-1277 in the development of hepatocellular carcinoma (HCC). HCC patients were identified from patients who were diagnosed with focal liver lesions using magnetic resonance imaging (MRI). The expression levels of miR-1277 in the serum of HCC patients and HepG2 cells were measured. Then miR-1277 mimic, miR-1277 inhibitor, or scramble RNA was transfected into HepG2 cells. The effects of miR-1277 overexpression and suppression on HepG2 cell proliferation, migration, and invasion were then investigated. Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related markers, including E-cadherin, β-catenin, and vimentin, were detected. Target prediction and luciferase reporter assay were performed to explore the potential target of miR-1277. miR-1277 was significantly downregulated in the serum of HCC patients and HepG2 cells. Suppression of miR-1277 promoted HepG2 cell proliferation, migration, and invasion, whereas overexpression of miR-1277 had opposite effects. In addition, after miR-1277 was suppressed, the expressions of E-cadherin and β-catenin were significantly increased, while the expressions of vimentin were markedly decreased. Bone morphogenetic protein 4 (BMP4) was identified as the direct target of miR-1277. Knockdown of BMP4 reversed the effects of miR-1277 suppression on HepG2 cell migration and invasion, as well as the expressions of E-cadherin, β-catenin, and vimentin. Our results indicate that downregulation of miR-1277 may promote the migration and invasion of HepG2 cells by targeting BMP4 to induce EMT. Combination of MRI and miR-1277 level will facilitate the diagnosis and treatment of HCC.


A monolayer-based setup for optical amplification.
Signal amplification has been demonstrated with surface-bound electrochromic complexes that can exist in one of two oxidation states (M2+/3+). Reaction of FeCl3 with covalently immobilized Os2+ complexes on glass substrates converts the metal centers from one oxidation state to the other. The formed Fe2+ reduces a series of Ru3+-based monolayers. The absorption of light is coupled with the oxidation state of the complexes and provides the output for the monolayer-based device. The gain of the setup can be controlled by the addition of a Fe2+ chelating ligand.


Antenatal and perinatal causes of handicap: definitions and size of the problem.
The conditions of childhood that follow prenatal or perinatal problems are defined. These conditions are mental retardation in varying degree, the cerebral palsies, the syndrome of minimal cerebral dysfunction, language disorders and defects of hearing and vision. The difficulties in accurately measuring disability and handicap are discussed and an estimate of the size of the problem is offered. The contribution made by the low birthweight group is also considered and it is pointed out that, although within this group there is a much higher incidence of problems, the majority of children with handicapping conditions were of normal birthweight.


Activated charcoal and resin haemoadsorbents: in vitro drug removal and blood compatibility studies.
An investigation has been made of the drug removal properties and blood compatibility of activated charcoal and resin haemoadsorbents . The adsorbents were Norit RBX1 peat-based extruded charcoal, spherical charcoal as used in the Sorin Biomedica Detoxyl 2 column and 2 cross-linked polystyrene-based macroreticular resins. Drug removal properties were assessed in terms of in vitro adsorption efficiency of each adsorbent for 11 different drugs. The blood compatibility of the charcoals and macroreticular resins was evaluated in an in vitro haemoperfusion circuit by measuring the changes in platelet and leucocyte levels in human blood caused by contact with the adsorbent. The results of the investigation indicate advantages in using spherical charcoal haemoadsorbents .


Prayer warriors: a grounded theory study of American Indians receiving hemodialysis.
The purpose of this classic grounded theory study was to explore what spirituality means to individuals who are American Indians receiving hemodialysis. Twelve women and 9 men ages 24 to 62, volunteered for this study. Informed consent was obtained, and in-depth interviews, field notes, and theoretical memos were completed. The metaphor "Prayer Warriors" described the core category of this study. Praying played a major role in the following categories: (a) suffering, (b) honoring spirit, (c) healing old wounds, and (d) connecting with community. Praying involved hard work, suffering, sweating, hunger, and passion, and was a powerful way to cope with the stress of hemodialysis.


Reacting to genetic risk: an experimental survey of life between health and disease.
Medical sociologists contend that we are living in an era of surveillance medicine, in which the emphasis on risk blurs the lines between health and disease. Yet, data to examine these claims are generally drawn from patients, raising questions about whether this modern experience of medical risk extends beyond the clinic to healthy people in the larger population. We use the specific case of genetic risk to construct a survey experiment designed to induce the conditions theorized by surveillance medicine. Each respondent in a nationally representative sample (N = 2,100) was assigned a genetic risk (20%, 30% . . . 80%) for a disease (colon cancer, heart disease, Alzheimer's disease) and asked about many potential reactions. We find that people in the general population-regardless of health status or family history-respond to hypothetical genetic risk information by wanting to take action, and their reactions are stronger in domains related to self and family than to community and polity.


[Diagnostic and treatment options for retinal arterial macroaneurysms in relation to our cases].
In our report, we present the history of four patients diagnosed with retinal arterial macroaneurysm associated with complications. Our aim is to present the varied appearance of the disease and to present the various therapeutic options. Retinal artery macroaneurysm is a rare, but potentially vision-threatening ophthalmic condition. Macroaneurysm develops from the arteriosclerotic transformation of the artery caused by high blood pressure. Macroaneurysms can be asymptomatic, or they can be associated with exudative or hemorrhagic complication which causes visual impairment. Depending on the symptoms, they can be treated with laser photocoagulation, intravitreal injections, or with vitrectomy. Our presented cases also illustrate that each case requires individual consideration because a uniform therapeutic recommendation is still yet to be developed. In addition to the ophthalmic treatment, it is extremely important to refer the patient to internal medicine. Orv Hetil. 2023; 164(42): 1673-1677.


Capparis spinosa L. aqueous extract evokes antidiabetic effect in streptozotocin-induced diabetic mice.
As the aqueous extract of Capparis spinosa (CS) possess antidiabetic effect, he present study aims to reveal the possible mechanism of action of CS in diabetic mice. Both single and repeated oral administrations of aqueous extract of CS were performed in multi-low dose streptozotocin-induced (MLDS) diabetic mice. Euglycemic hyperinsulinemic clamp was used in association with the endogenous glucose production (perfusion rate of 3-3H glucose) to evaluate the effect of CS aqueous extract on insulin sensitivity. Our study showed that aqueous extract of CS possess a potent hypoglycaemic activity in MLDS diabetic mice. Furthermore, the analysis perfusion of 3-3H glucose demonstrated the parallel decrease of basal endogenous glucose production (EGP) with the hypoglycaemic activity. EGP was lower in CS-Treated group when compared to the control group (p<0.001). The euglycemic hyperinsulinemic clamp technique demonstrated that CS treatment improves insulin sensitivity in peripheral tissues. We conclude that the antihyperglycemic effet CS is probably due to the inhibition of basal endogenous glucose production and the improvement of insulin sensitivity in MLDS diabetic mice.


Zone 2 flexor tendon injuries: Venturing into the no man's land.
Flexor tendon injuries are seen commonly yet the management protocols are still widely debated. The advances in suture techniques, better understanding of the tendon morphology and its biomechanics have resulted in better outcomes. There has been a trend toward the active mobilization protocols with development of multistrand core suture techniques. Zone 2 injuries remain an enigma for the hand surgeons even today but the outcome results have definitely improved. Biomolecular modulation of tendon repair and tissue engineering are now the upcoming fields for future research. This review article focuses on the current concepts in the management of flexor tendon injuries in zone 2.


Practical Pest Management Strategies to Reduce Pesticide Runoff for Argentine Ant (Hymenoptera: Formicidae) Control.
The purpose of this study was to involve pest management professionals in the design of application techniques and strategies that would be efficacious and also reduce insecticide runoff. Our study involved measuring both the efficacy of treatments for the Argentine ant, Linepithema humile (Mayr), and the concurrent runoff of fipronil and pyrethroids. Two collaborating companies used low-impact protocols for controlling ants while minimizing runoff. Protocol 1 involved bimonthly treatments, while Protocol 2 was monthly. Both protocols involved an initial treatment with a fipronil spray around the foundation. At the garage door-driveway interface, the fipronil application was done as a pin stream for Protocol 1, and as a crack and crevice application in the expansion joint near the garage for Protocol 2. Protocol 1 replaced most pyrethroid sprays with bifenthrin granules placed around bushes and away from the driveway. For the next treatment on day 63, Protocol 1 also included cyfluthrin spray treatments around the house foundation and crack and crevice applications around the edge of the driveway. For the first treatment in Protocol 2, the fipronil spray was supplemented with spot treatments of cyfluthrin. For subsequent Protocol 2 treatments, botanical insecticides were applied. For weeks 1 and 2 posttreatment combined, Protocol 1 had significantly higher reductions in ant numbers compared with Protocol 2. Thereafter there were no significant differences between the protocols. Runoff of bifenthrin from the granules used with Protocol 1 was much lower than in previous trials involving bifenthrin sprays. Day 1 fipronil runoff for Protocol 2 was significantly lower than that for Protocol 1. This difference may be because of the crack and crevice application applied in Protocol 2. Cyfluthrin runoff was minimal for Protocol 2, which involved spot treatments to supplement the fipronil on day 1, or the botanical insecticides for subsequent treatments. Protocol 1 had a large peak of cyfluthrin runoff at day 63 corresponding to their house and driveway treatments.


Septins and K63 ubiquitin chains are present in separate bacterial microdomains during autophagy of entrapped Shigella.
During host cell invasion, Shigella escapes to the cytosol and polymerizes actin for cell-to-cell spread. To restrict cell-to-cell spread, host cells employ cell-autonomous immune responses including antibacterial autophagy and septin cage entrapment. How septins interact with the autophagy process to target Shigella for destruction is poorly understood. Here, we employed a correlative light and cryo-soft X-ray tomography (cryo-SXT) pipeline to study Shigella septin cage entrapment in its near-native state. Quantitative cryo-SXT showed that Shigella fragments mitochondria and enabled visualization of X-ray-dense structures (∼30 nm resolution) surrounding Shigella entrapped in septin cages. Using Airyscan confocal microscopy, we observed lysine 63 (K63)-linked ubiquitin chains decorating septin-cage-entrapped Shigella. Remarkably, septins and K63 chains are present in separate bacterial microdomains, indicating they are recruited separately during antibacterial autophagy. Cryo-SXT and live-cell imaging revealed an interaction between septins and LC3B-positive membranes during autophagy of Shigella. Together, these findings demonstrate how septin-caged Shigella are targeted for autophagy and provide fundamental insights into autophagy-cytoskeleton interactions.


Oral koilocytic dysplasia: long-term clinical control. A case report.
Leukoplakia, a common lesion in the oral cavity, is considered a premalignant lesion that can develop into carcinoma. In 1986, a group of pathologists described a variant of epithelial dysplasia and named it "koilocytic dysplasia" (KD). This article presents a case of KD that was identified for 12 years as "carcinoma in situ". Even after removal of the lesion, it recurred with no signs of malignancy. The histopathological findings revealed all of the signs of KD (koilocytosis, acanthosis, multinucleated keratinocytes and atypical mitoses). Liquid-based cytology and hybrid capture were performed to confirm the diagnosis. Despite a professional recommendation to have the lesion removed surgically, the patient chose periodic clinical control. The mechanism of HPV transmission in the oral cavity still remains partially unknown. Additional studies on this subject are required to better understand the role of HPV in cell transformation in the oral cavity.


Diabetes prevalence in rural Indigenous Guatemala: A geographic-randomized cross-sectional analysis of risk.
Developing countries and Indigenous populations are disproportionately affected by global trends in diabetes (T2DM), but inconsistent data are available to corroborate this pattern in Guatemala and indigenous communities in Central America. Historic estimates of T2DM, using a variety of sampling techniques and diagnostic methods, in Guatemala include a T2DM prevalence of: 4·2% (1970) and 8·4% (2003). Objectives of this geographically randomized, cross-sectional analysis of risk include: (1) use HbA1c to determine prevalence of T2DM and prediabetes in rural Indigenous community of Atitlán (2) identify risk factors for T2DM including age, BMI and gender. A spatially random sampling method was used to identify 400 subjects. Prevalence was compared using the confidence interval method, and logistic regression and linear regression were used to assess association between diabetes and risk factors. The overall prevalence of T2DM using HbA1c was 13·81% and prediabetes was also 13·81% in Atitlán, representing a tripling in diabetes from historic estimates and a large population with pre-diabetes. The probability of diabetes increased dramatically with increasing age, however no significant overall relationship existed with gender or BMI. Diabetes is a larger epidemic than previously expected and appears to be related to ageing rather than BMI. Our proposed explanations for these findings include: possible Indigenous unique genetic susceptibility to T2DM, shortcomings in BMI as a metric for adiposity in assessing risk, changes in lifestyle and diet, and an overall aging population. The conclusion of this study suggest that (1) T2DM in rural regions of Guatemala may be of epidemic proportion. With pre-diabetes, more than 25% of the population will be diabetic in the very near future; (2) Age is a significant risk factor in the Indigenous population but BMI is not. This suggests that in some populations diabetes may be a disease of ageing.


Tuning the Rectification Ratio by Changing the Electronic Nature (Open-Shell and Closed-Shell) in Donor-Acceptor Self-Assembled Monolayers.
This Communication describes the mechanism of charge transport across self-assembled monolayers (SAMs) of two donor-acceptor systems consisting of a polychlorotriphenylmethyl (PTM) electron-acceptor moiety linked to an electron-donor ferrocene (Fc) unit supported by ultraflat template-stripped Au and contacted by a eutectic alloy of gallium and indium top contacts. The electronic and supramolecular structures of these SAMs were well characterized. The PTM unit can be switched between the nonradical and radical forms, which influences the rectification behavior of the junction. Junctions with nonradical units rectify currents via the highest occupied molecular orbital (HOMO) with a rectification ratio R = 99, but junctions with radical units have a new accessible state, a single-unoccupied molecular orbital (SUMO), which turns rectification off and drops R to 6.


l-Alpha-acetylmethadol (LAAM): prognostic considerations.
The authors studied the responses of 28 adult male volunteers who were openly changed from methadone to l-alpha-acetylmethadol (LAAM) maintenance. They found that patients who had been receiving middle-range doses (50-70 mg) of methadone required a significantly lower mean increase in LAAM than patients who had been receiving either high or low methadone doses and that the patients who accepted LAAM differed significantly from those who did not in MMPI 2-point-code ratings and mean social adjustment scale scores. These findings may provide prognostic indicators for response to LAAM, a possible alternative to methadone.


Low-Intensity, High-Frequency Grazing Positively Affects Defoliating Behavior, Nutrient Intake and Blood Indicators of Nutrition and Stress in Sheep.
The intensity and frequency of grazing affect the defoliating strategy of ruminants, their daily nutrient intake, thus nutrition and physiological status. Italian ryegrass (Lolium multiflorum Lam.) pastures were grazed by sheep either under a low-intensity/high-frequency grazing strategy (Rotatinuous stocking; RN) with nominal pre- and post-grazing sward heights of 18 and 11 cm, respectively, or under a high-intensity/low-frequency strategy (traditional rotational stocking; RT) with nominal pre- and post-grazing sward heights of 25 and 5 cm, respectively. Treatments were arranged under a complete randomized design and evaluated over two periods, in different years. In 2017, the aim was to depict the type of bites that sheep perform during the grazing-down and associate them to the grazing management strategy according to their relative contribution to the diet ingested. In 2018 we estimated the total nutrient intake and evaluated blood indicators of the nutritional status and immune response to stress of sheep. The bite types accounting the most for the diet ingested by RN sheep were those performed on the "top stratum" of plants with around 20, 15, and 25 cm, whereas the type of bites accounting the most for the diet of RT sheep were those performed on "grazed plants" with around 10, 5, and ≤ 3 cm. In 2018, the RN sheep increased by 18% the total organic matter (OM) intake and by 20-25% the intake of soluble nutrients (i.e., crude protein, total soluble sugars, crude fat), digestible OM and of metabolizable energy, and had 17.5, 18, and 6.1% greater blood concentration of glucose, urea nitrogen (BUN) and albumin, respectively, but 17% lower blood neutrophil-to-lymphocyte (N:L) ratio. Sheep grazing vegetative Italian ryegrass pastures under the low-intensity/high-frequency grazing strategy (RN) ingested a diet of better quality from bites allocated on the top stratum of plants, had greater intake of soluble nutrients and blood parameters positively associated with nutritional status and immune response to stress.


One-pot synthesis of benzo[b]furan and indole inhibitors of tubulin polymerization.
Benzo[b]furan and indole analogues of some recently identified benzo[b]thiophene inhibitors of tubulin polymerization have been prepared, and their biological activity has been assessed. Several very potent analogues were identified.


Potential causes of spurious programming: report of a case.
The possibility of false or inadvertent reprogramming increases with the availability of different and more complex programming mechanisms. A case of spurious programming during application of the Vitatron MPA1 analyzer to a Medtronic impulse generator (IPG) is described and the nature of the phenomenon is explained. It is concluded that the introduction of a simple and standardized "security-maneuvre" to which every IPG will respond safely, in the event of fortuitous dysprogramming, is required.


Management of acute low back pain in emergency departments in São Paulo, Brazil: a descriptive, cross-sectional analysis of baseline data from a prospective cohort study.
To describe management strategies used in public emergency departments in a middle-income country for patients with acute non-specific low back pain. A descriptive, cross-sectional analysis of baseline data from a prospective cohort study. A study with 600 patients with low back pain presenting in four public emergency departments from São Paulo, Brazil was conducted. Diagnostic tests, pharmacological interventions, and/or referral to other healthcare professionals were collected. Descriptive analyses were used to report all outcomes. Of all patients, 12.5% (n=75) underwent some diagnostic imaging tests. Medication was administered to 94.7% (n=568) of patients. The most common medications were non-steroidal anti-inflammatory drugs (71.3%; n=428), opioids (29%; n=174) and corticosteroids (22.5%; n=135). Only 7.5% (n=45) of patients were referred to another type of care. There is a need for research data on low back pain from middle-income countries. There was an acceptable rate of prescription for diagnostic imaging tests. However, there were high medication prescriptions and small rates of referrals to other healthcare services. Our findings indicate that there is still a need to implement best practices in the management of acute low back pain at public emergency departments in Brazil.


All-Hydrocarbon Staples and Their Effect over Peptide Conformation under Different Force Fields.
Olefinic staples enhance α-helical content and conformational stability in peptides, maintaining a structural scaffold that allows the emulation of specific regions of protein surfaces for therapeutical purposes. The ability to anticipate the efficacy of adding a staple to a peptide through computational simulations may contribute to lowering the costs associated with rational drug design. We evaluated the capabilities of different force fields to reproduce the effect of all-hydrocarbon staples in molecular dynamics simulations. Using the AMBER99SB-ILDN, CHARMM36, and GROMOS54A7 force fields and two distinct initial conformations, we compared our results to experimentally obtained circular dichroism data. The GROMOS54A7 united-atom force field seems to be more accurate compared with all-atom force fields, despite being unable to reproduce the effect of the staple in some of the simulated systems. With further force field enhancements, MD simulations may be used to anticipate conformational effects of all-hydrocarbon staples in peptides.


Direct dynamics simulations of O(3P) + HCl at hyperthermal collision energies.
The dynamics of the O(3P) + HCl reaction at hyperthermal collision energies were investigated using the quasiclassical trajectory method. Stationary points on the OClH 3A" and 3A' potential energy surfaces (PESs) were also examined. The lowest transition state leading to OCl + H on the 3A" surface is 2.26 eV above the reagents at the CCSD(T)/cc-pVTZ level of theory. This saddle point is bent and product-like. Direct dynamics calculations at the MP2/cc-pVTZ level of theory were used to investigate the excitation functions for OH + Cl, OCl + H, and O + H + Cl formation. OCl is formed mainly from small-impact-parameter collisions, and the OCl + H excitation function peaks around 5 eV, where it is similar in magnitude to the OH + Cl excitation function. The shape of the OCl + H excitation function is discussed, and features are identified that should be general to hyperthermal collision dynamics.


Detection of adulterated Ginkgo biloba supplements using chromatographic and spectral fingerprints.
The fingerprints of 18 commercially available Ginkgo biloba supplements, 12 samples of raw G. biloba leaves, and three G. biloba standard reference materials from the National Institute of Standards and Technology were acquired directly (no chromatography) by UV spectrometry and after separation using HPLC with a diode array detector. The fingerprints consisted of the UV spectral images, the chromatographic images, and the areas of the 21 most prominent chromatographic peaks. Data were analyzed by principal component analysis and one-class soft independent modeling of class analogy (SIMCA). It was determined that three of the commercial products were adulterated with rutin, four with quercetin, and one with an unidentified flavonol glycoside. One-class SIMCA of the authentic products allowed the adulterated products to be easily distinguished using Q-residuals. Authentic supplements and raw leaf materials were easily distinguished. The finely powdered samples were also analyzed by near-IR (NIR) spectrometry. The authentic and adulterated products could not be distinguished by NIR spectrometry because of the excipients.


[Effects of ginkgolides on gene expression of hepatic cytochrome P-450 in rats].
To observe the effects of ginkgolides on gene expression of hepatic cytochrome P-450 in rats. Sprague-Dawley rats were administered ginkgolides (100 mg x kg(-1) body weight) through oral gavage once daily for four consecutive days. The level of gene expression in liver tissues was analyzed by competitive reverse transcription-polymerase chain reaction (competitive RT-PCR). A single and prospective band of CYP1A1, CYP1A2, CYP2B1/B2, CYP2C11, CYP2E1, CYP4A1 and cyclophilin was observed after polymerase chain reaction (PCR) when the reactive system of reverse transcription (RT) had no target RNA, which confirmed the competitor had a specific capacity to bind to the CYP or cyclophilin primer. CYP1A1 mRNA was not dectectable in the livers of untreated control rats and ginkgolides-treated rats. The levels of CYP2C11 and CYP2E1 were not changed by ginkgolides treatment. In contrast, the levels of gene expression for CYP1A2 and CYP2B1/B2 were decreased, however, the levels of gene expression for CYP3A1 and CYP4A1 in ginkgolides group were distinctly increased compared with the control. A specific effect of ginkgolides on cytochrome P-450 gene expression was observed in this investigation. Ginkgolides had various effects on different cytochrome P-450 isoforms.


The Sigma class glutathione transferase from the liver fluke Fasciola hepatica.
Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity.


In vitro inhibition of porcine cytochrome P450 by 17β -estradiol and 17α-estradiol.
Sexually mature pigs are known to possess high concentrations of testicular steroids, which have been shown to change the activities of cytochrome P450 in vitro. The aim of the present study was to evaluate the regulation of CYP1A and CYP2E1 activity by the steroids dihydrotestosterone (DHT), 3β-androstenol, 17β-estradiol and 17α-estradiol. Catalytic activities of 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) were used as markers of CYP1A activities, while p-nitrophenol hydroxylase (PNPH) was used as a marker of CYP2E1 activities. Of the steroids tested, only 17β-estradiol and 17α-estradiol inhibited EROD and MROD activities. This inhibition was observed when a steroid concentration of 100 µM was used, while lower concentrations showed no inhibitory effect. PNPH activities were inhibited only by 100 µM of 17β-estradiol. The significance of these results in vivo is unknown because inhibition was only found when concentrations of estrogens higher than physiological levels were used. Nevertheless, the results provided further evidence on the important role of estrogens in regulation of porcine cytochrome P450 activities.


Treatment of chronic gastric ulcer with gefarnate: a long-term controlled therapeutic trial.
A long-term controlled therapeutic trial of gefarnate (600 mg daily) in the treatment of chronic gastric ulcer was carried out in 32 patients. Assessment was based on the clinical course and on repeated radiological and endoscopic examinations, which were performed after 3-months' treatment, at the end of the 1-year trial period, and towards the end of a follow-up period of approximately 2 1/2 to 3 1/2 years. In men with gastric ulcer, gefarnate proved to be highly effective, with 10 out of the 11 patients who received this treatment showing persistent healing of the ulcer compared with only 4 out of the 11 who were on dummy treatment. In the very small group of women it was not possible to show any difference between treatments. No adverse reactions to gefarnate occurred. These results suggest that gefarnate is a safe and effective treatment for chronic gastric ulcer.


Effects of FGF10 on bovine oocyte meiosis progression, apoptosis, embryo development and relative abundance of developmentally important genes in vitro.
Fibroblast growth factor (FGF10) acts at the cumulus oocyte complex, increasing the expression of cumulus cell expansion-related genes and oocyte competency genes. We tested the hypothesis that addition of FGF10 to the maturation medium improves oocyte maturation, decreases the percentage of apoptotic oocytes and increases development to the blastocyst stage while increasing the relative abundance of developmentally important genes (COX2, CDX2 and PLAC8). In all experiments, oocytes were matured for 22 h in TCM-199 supplemented with 0, 2.5, 10 or 50 ng/ml FGF10. In Experiment 1, after maturation, oocytes were stained with Hoechst to evaluate meiosis progression (metaphase I, intermediary phases and extrusion of the first polar body) and submitted to the TUNEL assay to evaluate apoptosis. In Experiment 2, oocytes were fertilized and cultured to the blastocyst stage. Blastocysts were frozen for analysis of COX2, CDX2 and PLAC8 relative abundance. In Experiment 1, 2.5 ng/ml FGF10 increased (p < 0.05) the percentage of oocytes with extrusion of the first polar body (35%) compared to 0, 10 and 50 ng/ml FGF10 (21, 14 and 12%, respectively) and FGF10 decreased the percentage of oocytes that were TUNEL positive in all doses studied. In Experiment 2, there was no difference in the percentage of oocytes becoming blastocysts between treatments and control. Real-time RT-PCR showed a tendency of 50 ng/ml FGF10 to increase the relative abundance of COX2 and PLAC8 and of 10 ng/ml FGF10 to increase CDX2. In conclusion, the addition of FGF10 to the oocyte maturation medium improves oocyte maturation in vitro, decreases the percentage of apoptotic oocytes and tends to increase the relative abundance of developmentally important genes.


Daytime decrease of prolactin levels is associated with PCOS regardless to nutritional status and other hormones levels.
The aim of the study is to analyze daytime changes of prolactin level depending on nutritional status and polycystic ovary syndrome (PCOS). One hundred and fifteen (69 normal weight, 21 overweight and 25 obese) diagnosed with PCOS and 77 (37 normal weight, 18 overweight and 22 obese) women - Non-PCOS without concomitant diseases were enrolled. Body mass and height were measured and BMI was calculated. Serum concentrations of FSH, LH, E2, testosterone, TSH and PRL were determined morning 6.00 a.m. after wake. Second measurement of PRL was performed at 4 p.m. The daytime decrease of prolactin level was higher in PCOS than in Non-PCOS group regardless of nutritional status (normal weight 35.8 ± 26.0 vs. 24.3 ± 15.3 ng/mL; overweight 28.5 ± 25.4 vs. 17.5 ± 8.8 ng/mL and obese 23.2 ± 21.1 vs. 18.4 ± 11.6 ng/ml, respectively). However, in both PCOS and Non-PCOS daytime changes of prolactin level were higher in normal weight than overweight and obese women (35.8 ± 26.0 vs. 28.5 ± 25.4 vs. 23.2 ± 21.1 ng/mL and 24.3 ± 15.3 vs. 17.5 ± 8.8 vs. 18.4 ± 11.6 ng/mL, respectively). The multivariate regression analysis revealed that the daytime changes of prolactin level are proportional to TSH concentration and coexistence of PCOS as well as inversely relative to BMI. In conclusions, our results suggest that overweight and obesity decreased morning PRL level and impaired its daytime decrease, but coexistence of PCOS enlarged its.


Accelerated K-means clustering in metric spaces.
The K-means method is a popular technique for clustering data into k-partitions. In the adaptive form of the algorithm, Lloyds method, an iterative procedure alternately assigns cluster membership based on a set of centroids and then redefines the centroids based on the computed cluster membership. The most time-consuming part of this algorithm is the determination of which points being clustered belong to which cluster center. This paper discusses the use of the vantage-point tree as a method of more quickly assigning cluster membership when the points being clustered belong to intrinsically low- and medium-dimensional metric spaces. Results will be discussed from simulated data sets and real-world data in the clustering of molecular databases based upon physicochemical properties. Comparisons will be made to a highly optimized brute-force implementation of Lloyd's method and to other pruning strategies.


Metastatic chordoma of the breast: an extremely rare lesion mimicking mucinous cancer.
Metastases in the breast are rare, with metastatic chordoma being one of the rarest. To our knowledge, only one such case has previously been published in the literature. We report a case of a 74-year-old woman who presented with a palpable lump in her right breast. The lump was mammographically suggestive of mucinous breast cancer because it was a solitary, small, circular, and moderately dense lesion yielding abundant mucoid aspirate. The tumor resembled mucinous carcinoma upon histologic and immunohistochemical examination: it had a mucinous stroma, and the tumor cells strongly expressed epithelial markers. However, the patient had previously undergone surgery for a recurrent sacral chordoma. In addition to the clinical history, the presence of typical physaliferous cells expressing neither estrogen receptors nor cytokeratin 7, but staining positively for S-100 protein, allowed the proper diagnosis. Although extremely rare, metastatic chordoma may represent a challenge in the differential diagnosis of breast lesions. Discriminating metastases of mucin-producing tumors in the breast from primary mucinous carcinomas is important with regard to the striking difference in prognosis of these lesions.


Using Novel Technology to Determine Mobility Among Hospitalized Heart Failure Patients: A Pilot Study.
Patients with heart failure (HF) experience frequent rehospitalizations and poor functional capacity. Early hospital mobility may prevent functional decline, but mobility patterns among hospitalized HF patients are not yet known. Accelerometers may provide a method to monitor and measure patient mobility objectively. Therefore, the purpose of this study was to describe mobility and function using accelerometers among hospitalized HF patients. Wireless accelerometers were attached to the thigh and ankle of previously ambulatory hospitalized HF patients (n = 32) continuously for up to 5 days, beginning on the second day of hospitalization. The mean proportion of time spent lying, sitting, and standing or walking daily was measured. Ability to perform activities of daily living (ADLs) and physical function was measured using the Katz Index and Short Physical Performance Battery (SPPB). Patients' mean age was 58.2 ± 13.6 and 78% (n = 25) were male. Mean New York Heart Association Class upon enrollment and at the end of the study period was 2.9 ± 0.8 and 2.2 ± 0.8 respectively. A mean Katz Index of 5.6 ± 1.1 upon enrollment demonstrated minimal dependence on assistance for completion of ADLs (possible scores 0 - 6). However, mobility testing revealed low physical function, with mean SPPB scores of 6.4 ± 3.1 (possible scores 0 - 12). During hospitalization, 70% of the measured hospital stay (16.8 hours/day) was spent lying in bed. The average time spent standing or walking was 4.1%, or 59 minutes per day and the range was 0-10% (0 - 150 minutes). Immobility was pervasive as HF patients spent almost all of their time sitting or lying in bed despite their baseline ambulatory status and improved NYHA class.


Specific circularly polarized luminescence of Eu(iii), Sm(iii), and Er(iii) induced by N-acetylneuraminic acid.
Recently, we found that the Raman optical activity (ROA) technique can be used to monitor even a weak lanthanide luminescence including circular polarization. In the present study we compare circularly polarized luminescence (CPL) spectra of Eu(iii), Sm(iii), and Er(iii) induced by aqueous solution of sialic acid. For Eu providing the strongest signal a chelation model was proposed where the carboxyl adopts the axial conformation and carboxyl oxygen is attached to Eu(iii).