cssi/SciSciGPT-SciSciNet huggingface dataset:
Cardiovascular risk and combined oral contraceptives: clinical decisions in settings of uncertainty

Although generally safe, combined oral contraceptives (COCs) are associated with risks, including an estimated 2-fold increased relative risk of cardiovascular events. For most women taking COCs for contraception, absolute cardiovascular risks are very low, and the overall risks of COCs are outweighed by the risks of unwanted pregnancy. Nonetheless, risks of COCs may be excessive in some women, and both the American College of Obstetricians (ACOG) and the World Health Organization (WHO) have offered contraindications for COC use. Complicating this issue, COCs are commonly used for reasons other than contraception (eg, polycystic ovary syndrome, which is associated with subfertility and cardiovascular risk factors). Thus, in some clinical scenarios, ACOG and WHO guidelines may offer incomplete guidance regarding whether COC use would be associated with an unacceptable risk-benefit ratio. We propose that cardiovascular risk calculators may be helpful in some patients, as an adjunct to ACOG and WHO guidelines, by allowing physicians to estimate the attributable risk of COC-related cardiovascular events.
Discovery of Novel α4β2 Neuronal Nicotinic Receptor Modulators through Structure-Based Virtual Screening

We performed a hierarchical structure-based virtual screening utilizing a comparative model of the human α4β2 neuronal nicotinic acetylcholine receptor (nAChR) extracellular domain. Compounds were selected for experimental testing based on structural diversity, binding pocket location, and standard error of the free energy scoring function used in the screening. Four of the eleven in silico hit compounds showed promising activity with low micromolar IC50 values in a calcium accumulation assay. Two of the antagonists were also proven to be selective for human α4β2 vs human α3β4 nAChRs. This is the first report of successful discovery of novel nAChR antagonists through the use of structure-based virtual screening with a human nAChR homology model. These compounds may serve as potential novel scaffolds for further development of selective nAChR antagonists.
The World Journal of Surgery Welcomes New Associate Editors

We at the World Journal of Surgery welcome two new Associate Editors to our editorial team, Julie Ann Sosa, MD MA FACS, and Janice Pasieka FRCS (Can), from the International Association of Endocrine Surgeons (IAES). Drs. Sosa and Pasieka are endocrine surgeon-scientists of great stature. Their primary mission will be to decide the fate of the many endocrine articles that the journal receives every month. The original scientific contributions in endocrine surgery published in the World Journal of Surgery (WJS) represent the best science and practice of endocrine surgery around the world. The IAES is an integrated society of the ISS-SIC and remains one of the strongest anchors for our journal. Julie Ann Sosa, MD MA FACS, is Professor of Surgery and Medicine (Oncology) at Duke University, Durham, North Carolina, USA, where she serves as Chief of Endocrine Surgery and Director of Health Services Research in Surgery. She also leads the Endocrine Neoplasia Diseases Group at the Duke Cancer Institute and the Duke Clinical Research Institute. Her clinical practice and research focus on thyroid cancer. She is the author of more than 160 peer-reviewed publications in outcomes analysis, cost-effectiveness/decision analysis, meta-analysis, and survey-based methodologies, as well as stem cell research. She has been the principal investigator (PI) or an investigator on international trials of novel advanced thyroid cancer therapies. She is vice president of the American Association of Endocrine Surgeons (AAES) and serves on practice guidelines committees for the American Thyroid Association and the National Comprehensive Cancer Network (NCCN). She brings a wealth of editorial experience to the WJS, from her editorial roles on the Journal of Surgical Research (Associate Editor), Current Opinion in Oncology, and the Journal of Thyroid Research. Dr. Sosa was born in Montreal and raised in upstate New York. She received her AB at Princeton, her MA at Oxford, and her MD at Johns Hopkins, where she also completed the Halsted residency and a fellowship in surgical oncology.
Abstract 574: α-santalol induces caspase-dependent apoptosis and G2/M phase cell cycle arrest in human breast cancer cells

Alpha-santalol, an active component of sandalwood oil, has been shown to have chemopreventive effects on skin cancer both in vitro and in vivo. However, effects of alpha-santalol on other types of cancer have not been studied. In this study, we examine the effects and mechanisms of action of alpha-santalol on human breast cancer cells using estrogen receptor (ER)- positive (MCF-7) and estrogen receptor- negative (MDA-MB-231) breast cancer cell lines. MTT and BrdU cell proliferation ELISA results showed inhibition of cell viability and proliferation in a time and dose-dependent manner in both cell lines. Alpha-santalol at 25-150 µM concentration decreased cell viability after 12h treatment. In addition, TUNEL assay and flow cytometry results revealed that alpha-santalol significantly induced apoptosis in MCF-7 and MDA-MB-231 cells. Further, immunoblotting and caspase activity assays showed involvement of caspase-3, caspase-8 and caspase-9 in apoptotic cell death. Induction of apoptosis by alpha-santalol was further confirmed by detecting the cleavage of Poly (ADP-ribose) Polymerase (PARP) through western blotting. Cell cycle distribution of alpha-santalol treated MFC-7 and MDA-MB-231 cells were analyzed by fluorescence- activated cell sorting (FACS) analysis of propidium iodide staining. We observed that alpha-santalol treatment arrests cell cycle at G2/M phase at 25µM −75µM concentration in both cell lines. Taken together, our studies reveal a potential mechanism for the chemopreventive effect of alpha-santalol on ER- positive and ER- negative breast cancer cells through induction of apoptosis and cell cycle arrest at G2/M phase. Alpha-santalol could be effective for the prevention and treatment of breast cancer. (Supported by Translational Cancer Research Center funded by South Dakota, Governors Office of Economic Development) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 574. doi:1538-7445.AM2012-574
A ricin agglutinin-resistant clone of Leishmania donovani deficient in lipophosphoglycan.

A variant cell line of Leishmania donovani (named R2D2) has been selected for resistance to the cytotoxic lectin ricin agglutinin and shown to be defective in the synthesis of its major glycoconjugate lipophosphoglycan. Compared to the parental line, R2D2 cells showed a marked resistance to the toxic effects of ricin and an increased sensitivity toward concanavalin A. The synthesis of lipophosphoglycan by R2D2 cells was judged to be < 1% relative to that of wildtype cells as determined by incorporation of radioactive mannose and galactose and by electrophoretic and chromatographic analyses. Although lacking lipophosphoglycan, R2D2 parasites were capable of infecting cultured U937 macrophages.
A COMPARISON OF MYO‐INOSITOL‐1‐PHOSPHATE SYNTHASE ACTIVITY IN EUGLENA GRACILIS AND IN A BLEACHED MUTANT

SUMMARY 1L-myo-Inositol-l-phosphate synthase, EC 5.5.1.4, was extracted from light- and dark-grown Euglena gracilis cells and a bleached mutant (W3BUL). Within experimental error no differences in synthase activity were detected among these three cell types.
Application of gonadotrophin releasing hormone as therapeutic agent in animal reproduction

Abstract Therapeutic application of gonadotrophin releasing hormone (GnRH) and its analogs was limited initially to the treatment of cystic follicular degeneration in cows. The role of GnRH was subsequently expanded to control of normal ovarian follicles for fertility enhancement in repeat breeder cows, and regulation of the dominant follicle in estrus synchronization programs as well as for protection of some slowly developing bovine conceptuses. Therapeutic use of GnRH is rare in small ruminants where its application is focused primarily on out-of-season breeding. In pigs GnRH is used in reproductive management for induction of estrus in prepubertal gilts and postpartum sows, as well as for increasing litter size. In horses GnRH is also used for breeding management specifically to schedule ovulation. GnRH seeks to replace human chorionic gonadotrophin because of the latter's propensity to cause antibody formation after repeated use. However, GnRH must be given repeatedly, at frequent intervals, by continuous infusion or by implant to be effective in the mare. Stimulation of follicular development and ovulation are dependent on the amount of GnRH given. While there are no current, practical clinical applications in dogs and cats, there is considerable interest in the chronic administration of GnRH as a contraceptive agent. Immunization against GnRH can also have a contraceptive effect in dogs.
Mixed substituent poly[(vinyloxy)cyclotriphosphazenes]

The mixed substituent cyclophosphazene monomers N3P3Cl4(OCHCH2)(OCH2CF3) (2) and N3P3Cl3(OCHCH2) (OCH2CF3)2 (3) undergo polymerization under radical initiation conditions to yield the mixed substituent poly[(vinyloxy)cyclotriphosphazenes] [CH2CH(ON3P3Cl4(OCH2CF3))]n(5) and [CH2CH(ON3P3Cl3(OCH2CF3)2)]n (6), respectively. A significant, progressive reduction in molecular weight compared to the parent polymer of the series [CH2CH(ON3P3Cl5)]n (4) was observed and attributed to increased chain transfer. The thermal decomposition of 5 and 6 is similar to that observed for 4 with an exothermic elimination of HCl at modest temperatures. An alternative synthetic pathway involving nucleophilic substitution reactions of 4 provided [CH2CH(ON3P3(OCH2CF3)5)]n (7), [CH2CH(N3P3Cl2(OC6H5)3)]n (8A), [CH2CH(ON3P3Cl1.7(OC6H5)3.3)]n (8B), [CH2CH(ON3P3Cl1.5(NHCH3)3.5)]n (9), [CH2CH(ON3P3Cl3.8 (N(CH2CH3)2)1.2]n (10A), [CH2CH(ON3P3Cl3.4(N(CH2CH3)2)1.6)]n (10B), and [N3P3Cl2(OCHCH2)(N(CH3)2)]n, (11). The thermal behaviors of all of the new polymers were examined by TGA, DTA, DSC, and pyrolysis mass spectrometry. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013
A tungsten-in-glass iontophoresis assembly for studying input-output relationships in central neurons

Abstract A method is described for the production of an electrode capable of monitoring and modulating the input-output relationship of thalamic neurons. Tungsten-in-glass electrodes were manufactured with the ability to simultaneously record lateral geniculate nucleus action potentials and associated, retinally evoked S-potentials. The recording electrodes were mounted onto multibarreled micropipettes with iontophoretic capability. The completed electrode assembly permitted micropharmacological modulation of the fraction of lateral geniculate nucleus output spikes to retinal input spikes (the transfer ratio). Iontophoretically applied α-aminobutyric acid (GABA) decreased the transfer ratio, an effect countered by the GABA A antagonist, bicuculline. Elevated transfer ratios produced by stimulation of an afferent pathway originating in the parabrachial region of the brainstem were decreased by concurrently applied GABA. The fabrication of this electrode assembly employs simple modifications of existing techniques and separate construction of recording and iontophoretic elements to provide high-quality single-unit recordings coupled with micropharmacological function.
The Ontogeny of Blood Cells, Complement, and Immunoglobulins in 3- to 12-Week-Old 15I5-B Congenic White Leghorn Chickens

Abstract Six partially developed line 15I5-B congenic White Leghorn chicken strains were used to investigate age and B haplotype effects on hematocrit, total and differential leukocyte counts, hemolytic complement, immunoglobulins, and body weights. The .C-12 line had the lowest hematocrit values throughout the study. The .15I-5 line always had the highest mean hematocrit value and differed from the .C-12 and .P-13 lines at 3, 8, and 12 weeks, as well as lines .N-15 and .6-2 at 12 weeks. Ontogenically, the total leukocyte, hemolytic complement, immunoglobulins, and body weight values increased after 3 weeks in all lines. Lymphocytes were the predominant leukocyte after 3 weeks in all lines studied. At 12 weeks, the .C-12 line had the highest total leukocytes, heterophils, lymphocytes, and monocytes among the lines studied. The .6-2 line had a significantly higher hemolytic complement level than the .P-13 or the .C-12 line at all 3 ages, and at 12 weeks it also differed from the .7-2 line. The lines were found to be comparable for immunoglobulin classes M and G. In this study the line 15I5-B congenic lines differ for the traits of hematocrit and hemolytic complement level, and the results suggest the difference may be determined by genes in the B complex.
Treatment of hemolytic disorders

Abstract Therapy currently recommended for the hemolytic disorders discussed in this paper is summarized in Table I.
An inverse problem for a differential operator with a mixed spectrum

and that the continuous spectrum of L consists of only a finite number of finite intervals and one infinite interval. Under these assumptions it will be shown that the specification of a finite number of eigenvalues will lead to the determination and construction of a unique potential q(t). The authors plan to discuss the relationship between these potentials and the K dV equation in a future publication.
Mechanical transduction of nitric oxide synthesis in the beating heart.

Abstract NO alters contractile and relaxant properties of the heart. However, it is not known whether changes in ventricular loading conditions affect cardiac NO synthesis. To understand this potential contractile-relaxant autoregulatory mechanism, production of cardiac NO in response to mechanical stimuli was measured in vivo using a porphyrinic sensor placed in the left ventricular myocardium. The beating rabbit heart exhibited cyclic changes in [NO], peaking at 2.7±0.1 μmol/L near the endocardium and 0.93±0.20 μmol/L in the midventricular myocardium (concentrations were 15±4% lower in the rat heart). In the present study, we demonstrate for the first time that increasing or decreasing ventricular preload in vivo is followed by parallel changes in [NO], which may represent a novel autoregulatory mechanism to adjust cardiac performance or perfusion on a beat-to-beat basis. To quantify the relationship between applied force and NO synthesis, intermittent compressive or distending forces applied to ex vivo nonbeating hearts were shown to cause bursts of NO synthesis, with peak [NO] linearly related to ventricular transmural pressure. Experiments in which denuding cardiac endothelial and endocardial cells abrogated the NO signal indicate that these cells transduce mechanical stimulation into NO production in the heart. Taken together, these studies may help explain load-dependent relaxation, cardiac memory for mechanical events of preceding beats, diseases associated with myocardial distension, autoregulation of myocardial perfusion, and protection from thrombosis in the turbulent flow environment within the beating heart.
Positive margins after cervical conization as an indicator of residual dysplasia.

Abstract Objective: To determine the significance of positive margins of resection after cervical conization as an indicator of residual dysplasia. Materials and Methods: A retrospective analysis for patients who underwent cervical conization either by loop electrosurgical excision procedure or cold knife conization between 1986 and 1997 at Montefiore Medical Center and North Central Bronx Hospital. The factors evaluated included grade of dysplasia with respect to positive or negative margins and post-procedure follow-up. Differences among groups were evaluated using the χ 2 and Fisher’s Exact test. Results: Of a total of 179 patients, 99 had positive margins of resection and 80 had negative margins of resection. Twenty-six patients had CIN I, of which 10 had positive margins of resection and 16 had negative margins of resection. There were 30 patients with CIN II, of which 13 had positive margins and 17 had negative margins. One hundred fourteen patients had CIN III/carcinoma in situ (CIS), of which 68 had positive margins of resection while 46 had negative margins of resection. Nine patients had microinvasive disease (MIC), of which 8 had positive margins of resection and 1 had negative margin of resection. The correlation between higher grades of dysplasia and the likelihood of having positive margins was noted to be statistically significant ( P = .02). Patients were followed up from a period of 6 weeks to 5 years. Of the patients with CIN I and positive margins, 5 had a normal post-cone Papanicolaou smear while 2 had an abnormal post-cone Papanicolaou smear. Seven of 9 patients with CIN II and positive margins had normal initial post-procedure Papanicolaou smear while only 2 had abnormal initial post follow-up Papanicolaou smear. Twenty-five patients with CIN III/CIS and positive margins had normal Papanicolaou smears at their initial post-procedure follow-up while 36 patients had an abnormal initial follow-up. Six of 8 patients with MIC and positive margins had documented follow-up. Of these 6, 2 had normal post-procedure Papanicolaou smears while 4 had abnormal post-procedure Papanicolaou smears. This approaches statistical significance. Additionally, the incidence of residual disease was analyzed in hysterectomy specimens with respect to grade of dysplasia. No patients with CIN I and positive margins were treated with hysterectomy. Of the 3 patients with CIN II treated with hysterectomy, 2 had residual dysplasia. Of the 21 patients with CIN II/CIS who underwent hysterectomy, 10 had residual disease. Of the 5 patients with MIC who underwent hysterectomy, 3 had residual disease. Conclusion: The likelihood of positive margins of resection increases with higher dysplasia. The incidence of abnormal initial post-procedure Papanicolaou smear appears to be increased with increasing grade of dysplasia. Interestingly, there does not appear to be an increase in the incidence of residual dysplasia when hysterectomy is performed for positive margin of resection after conization for high grade dysplasia.
Control of Ehrlich cell division by zinc

The nutritional requirement for zinc in the proliferation of normal and malignant cells has been demonstrated in a number of animal studies. A distinction is made between the effect of zinc status upon the host during carcinogenesis and tumor growth. The present studies focus on the Ehrlich ascites tumor in mice fed a semipurified zinc-deficient diet along with defined concentration of zinc in the drinking water. This model of zinc deficiency is compared with others in which chelating agents are used to create zinc-deficient conditions or the microorganismEuglena gracilis is examined in a defined zinc-deficient medium. It is reported here that Ehrlich cells remain quiescent for several weeks in severely deficient mice, suggesting their restriction to a G1 or G0 state of the cell cycle. The kinetics of thymidine and uridine uptake and incorporation into DNA and RNA in Zn-normal and Zn-deficient tumors is consistent with the inhibition of thymidine kinase and DNA polymerase in the Zn-deprived system, but with little effect on RNA synthesis. The concentration of metabolites of these labeled nucleosides in Ehrlich cells is also consistent with a primary effect upon thymidine kinase. Although the ascites fluid Zn is depressed in Zn deficiency, total cellular zinc and its distribution among cell fractions is not significantly affected. It is suggested that these effects are specific in nature and not the result of a general lack of zinc for zinc metalloproteins and other binding sites in the cell.
Rhenium(I) isocyanide complexes

Two series of rhenium(I) isocyanide complexes having the general formulas Re(CO)5−nLnBr and [Re(CO)6−nLn]PF6 (L = CNMe, CNtol) are described. The former compounds are formed from Re(CO)5Br by direct carbonyl replacement using thermal or photolytic conditions, the extent of the reaction being determined by reaction temperature and time. An interesting conversion of fac-Re(CO)3L2Br to mer,trans-Re(CO)3L2Br on heating is noted. The third possible isomer having this stoichiometry, mer,cis-Re(CO)3L2Br, forms in photolytic reactions of Re(CO)5Br and L. Three possible Re(CO)2L3Br isomers were isolated, thermal reactions (toluene reflux) giving the mer,cis and fac isomers, photolytic reactions giving all three isomers. Isomers were generally separated by chromatography and their geometries ascertained from infrared data. More forcing reaction conditions eventually give Re(CO)L4Br, then ReL5Br and [ReL6]Br (L = CNtol only) or [Re(CO)L5]Br. The other ionic complexes are prepared from the substituted carbonyl halide, Re(CO)5−nLnBr, and added ligands in the presence of a halide acceptor. Generally, all reactions are much less facile than corresponding reactions in the manganese carbonyl series. Spectroscopic and electrochemical data are reported.
Lepidostroma vilgalysii, a new basidiolichen from the New World

The lichenized basidiomycete Lepidostroma vilgalysii from Mexico is described based on morphological analyses. The species is only the second representative of the family Lepidostromataceae documented from the New World, and is one of the few described lichens with an inverted morphology, with the algae in a layer at the base of the thallus. Molecular sequence data from the nuclear ribosomal LSU locus are used to confirm the placement of the holotype in Lepidostroma and to evaluate the molecular distinctiveness of the species from all other described species in the family and genus.
Enzymatic iron and uranium reduction by sulfate-reducing bacteria

Abstract The potential for sulfate-reducing bacteria (SRB) to enzymatically reduce Fe(III) and U(VI) was investigated. Five species of Desulfovibrio as well as Desulfobacterium autotrophicum and Desulfobulbus propionicus reduced Fe(III) chelated with nitrilotriacetic acid as well as insoluble Fe(III) oxide. Fe(III) oxide reduction resulted in the accumulation of magnetite and siderite. Desulfobacter postgatei reduced the chelated Fe(III) but not Fe(III) oxide. Desulfobacter curvatus, Desulfomonile tiedjei, and Desulfotomaculum acetoxidans did not reduce Fe(III). Only Desulfovibrio species reduced U(VI). U(VI) reduction resulted in the precipitation of uraninite. None of the SRB that reduced Fe(III) or U(VI) appeared to conserve enough energy to support growth from this reaction. However, Desulfovibrio desulfuricans metabolized H2 down to lower concentrations with Fe(III) or U(VI) as the electron acceptor than with sulfate, suggesting that these metals may be preferred electron acceptors at the low H2 concentrations present in most marine sediments. Molybdate did not inhibit Fe(III) reduction by D. desulfuricans. This indicates that the inability of molybdate to inhibit Fe(III) reduction in marine sediments does not rule out the possibility that SRB are important catalysts for Fe(III) reduction. The results demonstrate that although SRB were previously considered to reduce Fe(III) and U(VI) indirectly through the production of sulfide, they may also directly reduce Fe(III) and U(VI) through enzymatic mechanisms. These findings, as well as our recent discovery that the So-reducing microorganism Desulfuromonas acetoxidans can reduce Fe(III), demonstrate that there are close links between the microbial sulfur, iron, and uranium cycles in anaerobic marine sediments.
Nonlinear frequency conversion with passively Q-switched microchip lasers

Summary form only given. To generate the UV harmonics of the microchip laser output, we used antireflection-coated pieces of BaB/sub 2/O/sub 4/ oriented for type-I phase matching. In all cases, the crystals were 5-mm long, had flat faces, and were placed in the output path of the Nd:YAG laser with nointervening optics. The 532-nm green radiation was doubled to produce 266-nm UV radiation with 20% energy efficiency.
Flexible policies and IS-LM dynamics

Abstract A dynamic IS-LM model with a Phillips curve is used to analyze the consequences of familiar flexible government policies. The dynamic behavior of the model depends critically upon the monetary and fiscal policies followed by the government. If a passive stance is taken in which real government spending and the nominal money supply do not adapt to the course of economic events, then the model is unstable. The government can, however, follow simple policy rules which stabilize the economy. The most clearly stable policies involve the joint employment of monetary and fiscal policies.
‘It’s different for guys’: Gendered narratives of racial conflict among white California youth

As race talk has gained attention throughout the social sciences, sociocultural linguistics has become crucial in revealing how racial ideologies and identities are discursively produced. This article examines how race talk may reproduce racial binaries while perpetuating gender ideologies. Drawing on ethnographically collected narratives of conflict at an ethnoracially divided California high school, the analysis examines three discursive practices of racial reversal whereby white youth portray themselves as disadvantaged vis-a-vis their black peers: claims of 'reverse discrimination', narratives of racialized fear, and fight stories. Whereas white girls' narratives relied on racial vagueness, white boys' narratives highlighted racial difference, contrastive strategies that indicate the different racial stakes for white girls versus white boys at the school. The article demonstrates the necessity of examining race talk not only for its content but also for its discursive structure, its ethnographic and interactional context, its co-construction by the researcher, and its ideological effects.
Impact of state mental health parity laws on access to autism services.

ObjectivesThis study examined the effect of state mental health parity laws on family financial burden, satisfaction with health insurance, and receipt of needed mental health services for privately insured children ages three to 17 with autism spectrum disorder (ASD).MethodsData came from the 2005–2006 wave of the National Survey of Children With Special Health Care Needs. An econometric approach with instrumental variables was used to control for the nonrandom selection of states according to their mental health parity laws. The study analyzed data for 949 youths with ASD and private health insurance. Six outcome variables were examined, including several measures of family financial burden, satisfaction with health insurance, and receipt of needed mental health services.ResultsFamilies of children needing mental health services and living in a state with a strict parity law had a 61% higher probability of reporting out-of-pocket spending >$1,000 compared with those not living in a strict parity state. ...
Observation of an oscillating behavior in a superconducting transition

Abstract An oscillating behavior of superconducting transitions in a thorium disilicide-one atomic percent americium alloy has been observed.
Retention of participants in medication‐assisted programs in low‐ and middle‐income countries: an international systematic review

Background and aims Medication-assisted treatment (MAT) is a key component in overdose prevention, reducing illicit opiate use and risk of blood-borne virus infection. By retaining participants in MAT programs for longer periods of time, more noticeable and permanent changes in drug use, risk behavior and quality of life can be achieved. Many studies have documented retention in MAT programs in high-income countries, using a 50% average 12-month follow-up retention rate as a marker for a successful MAT program. This study contributes to a systematic understanding of how successful programs have been in retaining participants in low- and middle-income countries (LMIC) over time. Methods Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic literature search to identify MAT program studies that documented changes in retention over time for participants in buprenorphine and methadone programs in LMIC. Retention was measured for participants by length of follow-up, type of MAT and treatment dosage. Results There were 58 MAT program studies, with 27 047 participants eligible for inclusion in the review. Overall average retention after 12 months was 54.3% [95% confidence interval (CI) = 46.2, 63.7%]. Overall average retention was moderately good for both buprenorphine (48.3%, 95% CI = 22.1, 74.6%) and methadone (56.6%, 95% CI = 45.9%, 67.3%) after 12 months of treatment. Among programs using methadone there was no statistically significant difference in average retention by dosage level, and the 10 highest and lowest dosage programs obtained similar average retention levels after 12 months. Conclusion Medication-assisted treatment programs in low- and middle-income countries achieve an average 50% retention rate after 12 months, with wide variation across programs but little difference between those using buprenorphine versus methadone.
Colony-stimulating factors as promoters of ameboid microglia

Immunomodulators were tested for their ability to stimulate proliferation and biologic activity of ameboid microglia. Only the colony-stimulating factors (CSFs), multipotential-CSF (multi-CSF) and granulocyte/macrophage-CSF (GM-CSF), were potent mitogens for microglia. Other immunomodulators, including interleukin-1, interleukin- 2, interferon gamma, tumor necrosis factor, or granulocyte-CSF (G-CSF), had no effect upon microglial growth in vitro. Multi-CSF or GM-CSF were also observed to induce more rapid phagocytosis of polystyrene microspheres by cultured ameboid cells. In order to determine which immunomodulators alter brain inflammatory responses in vivo, we infused recombinant forms of GM-CSF, multi-CSF, macrophage-CSF, or G-CSF into the cerebral cortex of rats. Within 48 hr after infusion multi-CSF or GM-CSF stimulated the appearance of large numbers of mononuclear phagocytes at the site of injection. These same factors also accelerated the clearance of polystyrene microspheres from the brain. Our observations indicate that certain classes of immunomodulators which are mitogens and activators of ameboid microglia in vitro amplify the inflammatory response of the CNS in vivo by action upon intrinsic brain mononuclear phagocytes.
18F-FAHA PET for imaging histone deacetylase in lung cancer

411 Objectives Histone deacetylase has been imaged using 18F-FAHA and may serve as a marker to study epigenetics. We report evaluation of 18F-FAHA as a probe in the early diagnosis of lung cancer using longitudinal MicroPET/MicroCT 18F-FAHA studies of A/J mice treated with NNK. Methods 18F-FAHA radiosynthesis was carried out in specific activity of ~2 Ci/μmol as reported (Mukhopadhyay 2006). A/J mice acquired from Jackson Labs were divided into 2 groups: 1. Controls for CT/PET; 2. NNK treatment group for CT/PET. Group 2 animals received NNK (100 mg/kg, ip, weekly for 4 wks). Mice were injected 50-100 μCi i.v. 18F-FAHA and then scanned in Inveon MicroPET/CT under anesthesia using 2.0% isoflurane. Ex vivo PET/CT scans of lungs were also obtained on some mice after the in vivo scans. Sections (5 to 10μm thick) of the isolated lungs were prepared for H&E staining and autoradiographic studies. Results MicroCT revealed presence of lung nodules in 8 mo old mice while control mice were free of tumors. Little uptake of 18F-FAHA was in the control mice lungs while significant amount of 18F-FAHA was seen in the lungs of NNK treated mice. Quantitative analysis of the extent and amount of 18F-FAHA binding provided in vivo lung tumor/nontumor = >2.0. Studies of control A/J mice lungs showed little binding of 18F-FAHA, uniformly distributed. Ex vivo scans of the excised NNK and control mice lungs confirmed presence of extensive amounts of lung nodules seen by CT and confirmed by 18F-FAHA in the NNK mice while no tumors were detected in the control mice. Conclusions Our preliminary imaging studies with A/J mice lung cancer model suggests 18F-FAHA PET may allow the study of epigenetic mechanisms involved in NNK induced tumorigenesis in the lungs. Further studies on the ability of 18F-FAHA to detect the lung tumors earlier are underway
Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites

The secretion of Sonic hedgehog (Shh) from the notochord and floor plate appears to generate a ventral-to-dorsal gradient of Shh activity that directs progenitor cell identity and neuronal fate in the ventral neural tube. In principle, the establishment of this Shh activity gradient could be achieved through the graded distribution of the Shh protein itself, or could depend on additional cell surface or secreted proteins that modify the response of neural cells to Shh. Cells of the neural plate differentiate from a region of the ectoderm that has recently expressed high levels of BMPs, raising the possibility that prospective ventral neural cells are exposed to residual levels of BMP activity. We have examined whether modulation of the level of BMP signaling regulates neural cell responses to Shh, and thus might contribute to the patterning of cell types in the ventral neural tube. Using an in vitro assay of neural cell differentiation we show that BMP signaling markedly alters neural cell responses to Shh signals, eliciting a ventral-to-dorsal switch in progenitor cell identity and neuronal fate. BMP signaling is regulated by secreted inhibitory factors, including noggin and follistatin, both of which are expressed in or adjacent to the neural plate. Conversely, follistatin but not noggin produces a dorsal-toventral switch in progenitor cell identity and neuronal fate in response to Shh both in vitro and in vivo. These results suggest that the specification of ventral neural cell types depends on the integration of Shh and BMP signaling activities. The net level of BMP signaling within neural tissue may be regulated by follistatin and perhaps other BMP inhibitors secreted by mesodermal cell types that flank the ventral neural tube. SUMMARY
From Molecular Signal Activation to Locomotion: An Integrated, Multiscale Analysis of Cell Motility on Defined Matrices

The adhesion, mechanics, and motility of eukaryotic cells are highly sensitive to the ligand density and stiffness of the extracellular matrix (ECM). This relationship bears profound implications for stem cell engineering, tumor invasion and metastasis. Yet, our quantitative understanding of how ECM biophysical properties, mechanotransductive signals, and assembly of contractile and adhesive structures collude to control these cell behaviors remains extremely limited. Here we present a novel multiscale model of cell migration on ECMs of defined biophysical properties that integrates local activation of biochemical signals with adhesion and force generation at the cell-ECM interface. We capture the mechanosensitivity of individual cellular components by dynamically coupling ECM properties to the activation of Rho and Rac GTPases in specific portions of the cell with actomyosin contractility, cell-ECM adhesion bond formation and rupture, and process extension and retraction. We show that our framework is capable of recreating key experimentally-observed features of the relationship between cell migration and ECM biophysical properties. In particular, our model predicts for the first time recently reported transitions from filopodial to “stick-slip” to gliding motility on ECMs of increasing stiffness, previously observed dependences of migration speed on ECM stiffness and ligand density, and high-resolution measurements of mechanosensitive protrusion dynamics during cell motility we newly obtained for this study. It also relates the biphasic dependence of cell migration speed on ECM stiffness to the tendency of the cell to polarize. By enabling the investigation of experimentally-inaccessible microscale relationships between mechanotransductive signaling, adhesion, and motility, our model offers new insight into how these factors interact with one another to produce complex migration patterns across a variety of ECM conditions.
Increases in central blood volume modulate carotid baroreflex resetting during dynamic exercise in humans

We sought to determine if resetting of the carotid-vasomotor baroreflex function curve during exercise is modulated by changes in central blood volume (CBV). CBV was increased during exercise by altering: (1) subject posture (supine versus upright) and (2) pedal frequency (80 versus 60 revolutions min(-1) (r.p.m.)); while oxygen uptake ( ) was kept constant. Eight male subjects performed three exercise trials: upright cycling at 60 r.p.m. (control); supine cycling at 60 r.p.m. (SupEX) and upright cycling at 80 r.p.m. to enhance the muscle pump (80EX). During each condition, carotid baroreflex (CBR) function was determined using the rapid neck pressure (NP) and neck suction (NS) protocol. Although mean arterial pressure (MAP) was significantly elevated from rest (88 +/- 2 mmHg) during all exercise conditions (P < 0.001), the increase in MAP was lower during SupEX (94 +/- 2 mmHg) and 80EX (95 +/- 2 mmHg) compared with control (105 +/- 2 mmHg, P < 0.05). Importantly, the blood pressure responses to NP and NS were maintained around these changed operating points of MAP. However, in comparison to control, the carotid-vasomotor baroreflex function curve was relocated downward and leftward when CBV was increased during SupEX and 80EX. These alterations in CBR resetting occurred without any differences in or heart rate between the exercise conditions. Thus, increasing CBV and loading the cardiopulmonary baroreflex reduces the magnitude of exercise-induced increases in MAP and CBR resetting. These findings suggest that changes in cardiopulmonary baroreceptor load influence carotid baroreflex resetting during dynamic exercise.
Rapid identification of oxidation‐induced conformational changes by kinetic analysis

Protein oxidation by reactive oxygen species is known to result in changes in the structure and function of the oxidized protein. Many proteins can tolerate multiple oxidation events before altering their conformation, while others suffer gross changes in conformation after a single oxidation event. Additionally, reactive oxygen species have been used in conjunction with mass spectrometry to map the accessible surface of proteins, often after verification that the oxidations do not alter the conformation. However, detection of oxidation-induced conformational changes by detailed kinetic oxidation analysis of individual proteolytic peptides or non-mass spectrometric analysis is labor-intensive and often requires significant amounts of sample. In this work, we describe a methodology to detect oxidation-induced conformational changes in proteins via direct analysis of the intact protein. The kinetics of addition of oxygen to unmodified protein are compared with the kinetics of addition of oxygen to the mono-oxidized protein. These changes in the rate of oxidation of the oxidized versus the non-oxidized protein are strongly correlated with increases in the random coil content as measured by the molar ellipticity at 198 nm. This methodology requires only small amounts of protein, and can be done rapidly without additional sample handling or derivatization.
PRESSURE-INDUCED ORDERING IN (NI,MG)2SIO4 OLIVINE

An imaging-plate detector interfaced to a large-volume high-pressure device allows quantitative in situ powder X-ray diffraction measurements at the National Synchrotron Light Source (NSLS). High-quality diffraction patterns were recorded from an (Ni,Mg)2Si04 olivine solid-solution sample at 4 GPa and 800°C as a function of time using 3 min exposures at 40, 63, and 109 min. Refinement of the crystal structure indicated an increase in the ordering of Ni2+ and Mg2+ cations over the Ml and M2 sites at high pressure. The unit-cell volume was found to decrease with increasing ordering. Kinetic phenomena associated with the cation redistribution were observed on the time scale of tens of minutes. Extrapolation based on an exponential law of ordering relaxation toward equilibrium gave a distribution coefficient (KD)of 10.7(1) at 4 GPa and 800°C; the starting sample, which was annealed at 800 °c and room pressure, gave KD = 8.3(1).
More is more: the relationship between vocabulary size and word extension.

This study experimentally tested the relationship between children’s lexicon size and their ability to learn new words within the domain of color. We manipulated the size of 25 20-month-olds’ color lexicons by training them with two, four, or six different color words over the course of eight training sessions. We subsequently tested children’s ability to extend new color words to new instances. We found that training with a broader number of color words led to increased extension of new words. The results suggest that children’s learning history predicts their ability to learn new words within domains.
Neck and Back Pain. The Scientific Evidence of Causes, Diagnosis, and Treatment.

Alf L. Nachemson and Egon Jonsson, editors. Philadelphia: Lippincott Williams and Wilkins; 2000. 512 pages. $89.00. This textbook represents a four-year effort on the part of a highly competent interdisciplinary group of authors. It was edited by Nachemson, an internationally recognized orthopaedic surgeon, and Jonsson, a professor and the director of the Swedish Council on Technology Assessment in Health Care (SBU). The SBU is credited with having taken the initiative to …
Impact of a terminated wheat cover crop in irrigated corn on atrazine rates and water use efficiency

Abstract A study was conducted near Garden City, KS with irrigated corn to determine how the integration of a terminated winter wheat cover crop with various atrazine rates would affect Palmer amaranth control and corn water use efficiency (WUE). Without atrazine, the presence of a winter wheat cover crop, killed in the boot stage, resulted in a threefold weed biomass reduction in irrigated corn. The highest rate of atrazine completely masked the weed control effect of the cover crop, producing a greater than 15-fold reduction regardless of the presence or absence of the cover crop. A terminated winter wheat cover crop without atrazine elevated corn yield in only two of nine location-yr, and in one instance, depressed yield. However, a terminated wheat cover crop elevated corn yield in six of nine location-yr combinations when used in conjunction with 1.6 kg ha−1 atrazine. Although increases in WUE associated with reductions in soil water evaporation produced by the cover crop seemed to be responsible for...
The TEL Gene Contributes to the Pathogenesis of Myeloid and Lymphoid Leukemias by Diverse Molecular Genetic Mechanisms

The TEL gene, originally cloned by virtue of involvement in the t(5;12) chromosomal translocation associated with chronic myelomonocytic leukemia (CMML), has a remarkable capacity to contribute to the pathogenesis of human leukemias: (1) TEL has been implicated in both myeloid and lymphoid leukemias, acute and chronic leukemias, and leukemias of both pediatric and adult populations; (2) TEL can contribute either its DNA binding domain or a putative helix-loop-helix (HLH) domain to fusion proteins, and (3) TEL has been associated with a surprising variety of fusion partners in human leukemias, including genes for transcription factors, receptor and non-receptor tyrosine kinases, and putative transcriptional activating domains. In addition, recent evidence suggests that loss of function of TEL may also contribute to pathogenesis of malignancy. In this report, the diverse molecular genetic mechanisms of leukemogenesis mediated by the TEL gene will be discussed.
A Brief Review of Elasticity and Viscoelasticity for Solids

There are a number of interesting applications where modeling elastic and/or viscoelastic materials is fundamental, including uses in civil engineering, the food industry, land mine detection and ultrasonic imaging. Here we provide an overview of the subject for both elastic and viscoelastic materials in order to understand the behavior of these materials. We begin with a brief introduction of some basic terminology and relationships in continuum mechanics, and a review of equations of motion in a continuum in both Lagrangian and Eulerian forms. To complete the set of equations, we then proceed to present and discuss a number of specific forms for the constitutive relationships between stress and strain pro- posed in the literature for both elastic and viscoelastic materials. In addition, we discuss some applications for these constitutive equations. Finally, we give a com- putational example describing the motion of soil experiencing dynamic loading by incorporating a specific form of constitutive equation into the equation of motion.
« Faire parler les Dieux ». De la démocratie impossible au problème de la religion civile chez Rousseau

Au sens strict, la democratie est pour Jean-Jacques Rousseau la forme de gouvernement ou les corps du gouvernement et du peuple souverain sont identiques. Rousseau jugeant cette forme de gouvernement impossible, les commentateurs opposent a cette acception du terme une acception plus large : « democratie » designerait non plus la forme du gouvernement, mais celle de la souverainete populaire elle-meme. Cet article refute cette interpretation encore trop formelle. Partant du constat que la democratie est impossible comme forme de gouvernement, sauf pour « un peuple de dieux », je montre d’une part que son idee doit moins se comprendre comme forme que principe de gouvernement, et d’autre part que l’emploi du legislateur s’identifie rigoureusement a la mise en application initiale de ce principe. Je degage ensuite la relation entre ce sens principiel du concept de democratie et la vertu politique dont Rousseau reprend de facon critique le concept a Montesquieu. Dans la derniere partie, je discute du probleme que pose cette conception de la democratie et de la vertu – qui suppose qu’on mette la loi au-dessus de l’homme – dans le contexte historique et moral de l’Europe moderne ou la vertu ne peut plus s’appuyer sur un ressort religieux national.
Conflicts Religious and Secular

From the beginning, Zionism and Arabism shared the same intellectual patrimony and spoke the same language. Yet neither movement, just as each was trying to dignify a dormant nation, could bear an injury to its nationalist aspirations. A review of Arthur Hertzberg, The Fate of Zionism: A Secular Future for Israel & Palestine (HarperSanFrancisco, 2003).
American Catholics and the First Amendment: 1776-1840

THE CELEBRATION OF the bicentennial of the Constitution, and more specifically in 1989, of the Bill of Rights, demands that Americans reexamine the fundamental values they ac knowledge in that document, even if they do not always practice them. Liberty is at the heart of the American value system and has become one of the principal sources of American identity. The First Amendment begins by protecting liberties relating to religion: "Con gress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof." The primacy of religious liberty in the Bill of Rights was more than a literary convention. The bill's framers understood that in a religiously plural society both American identity and republican stability hinged on the free expression of religious beliefs. Religious minorities also appreciated that the liberties secured in the Constitution meant that they would enjoy safeguards against interference from the state, but that they also would have to compete in a voluntaristic religious environment for adherents. Such an arrangement promised a freedom, though, that might loosen re ligious ties. Perhaps more than any other group in the early republic, Catholics recognized, and wrestled with, the tensions between religious liberty at large and the need to preserve dogma and discipline within a church.