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There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission.

More than thirty years have passed since the discovery of the prion protein (PrP) and its causative role in transmissible spongiform encephalopathy. Since a combination of both gain- and loss-of-function mechanisms may underlay prion pathogenesis, understanding the physiological role of PrP may give important clues about disease mechanisms. Historically, the primary strategy for prion research has involved the use of human tissue, cell cultures and mammalian animal models. Nevertheless, experimental difficulties of in vivo studies and controversial observations obtained in these systems have stimulated the search for alternative animal models. PrPC is highly conserved in mammals, and PrPC-related orthologs are expressed in zebrafish, a vertebrate model organism suitable to study the mechanisms associated with human diseases. Invertebrate models, as they do not express PrPC have served to investigate the neurotoxic mechanisms of mammalian PrP. Here we overview most recent advances in the study of PrP function in normal and pathogenic conditions based on non-mammalian studies, highlighting the contribution of zebrafish, fly and worms to our current understanding of PrP biology.

The development of affordable and safe lithium-ion batteries (LIB) which feature high storage capacity represents one of the priority strategies toward further introduction of green technologies in our everyday life. This paper presents a study into the candidate composite anodes for high energy LIB; these utilize reversible high storage capacity of ions of lithium in the form of alloys of the latter with nano-sized silicon, imbedded in a soft-carbon matrix, which in turn, are deposited on a robust graphitic core. These structures allow an efficient contact between the constituents to be realized at the same time providing space for Si nano-particles during lithiation/de-lithiation process. The synthetic route described herein has a high potential for a cost-effective scale-up with the battery materials industry. Presented results demonstrate feasibility for creation of new active materials for the negative electrodes in LIB, which feature the storage capacity up to 700 mAh g[?]1 at C/2 and in excess of 1450 mAh g[?]1 at C/20 cycling rates, respectively. This work also shows that the use of acrylic binder has a positive effect on the overall system performance, as compared to state-of-the-art PVDF-based binder systems.

Serotonin (5HT) plays major roles in the physiological regulation of many behavioral processes, including sleep, feeding, and mood, but the genetic mechanisms by which serotonergic neurons arise during development are poorly understood. In the present study, we have investigated the development of serotonergic neurons in the zebrafish. Neurons exhibiting 5HT‐immunoreactivity (5HT‐IR) are detected from 45 h postfertilization (hpf) in the ventral hindbrain raphe, the hypothalamus, pineal organ, and pretectal area. Tryptophan hydroxylases encode rate‐limiting enzymes that function in the synthesis of 5HT. As part of this study, we cloned and analyzed a novel zebrafish tph gene named tphR. Unlike two other zebrafish tph genes (tphD1 and tphD2), tphR is expressed in serotonergic raphe neurons, similar to tph genes in mammalian species. tphR is also expressed in the pineal organ where it is likely to be involved in the pathway leading to synthesis of melatonin. To better understand the signaling pathways involved in the induction of the serotonergic phenotype, we analyzed tphR expression and 5HT‐IR in embryos in which either Hh or Fgf signals are abrogated. Hindbrain 5HT neurons are severely reduced in mutants lacking activity of either Ace/Fgf8 or the transcription factor Noi/Pax2.1, which regulates expression of ace/fgf8, and probably other genes encoding signaling proteins. Similarly, serotonergic raphe neurons are absent in embryos lacking Hh activity confirming a conserved role for Hh signals in the induction of these cells. Conversely, over‐activation of the Hh pathway increases the number of serotonergic neurons. As in mammals, our results are consistent with the transcription factors Nk2.2 and Gata3 acting downstream of Hh activity in the development of serotonergic raphe neurons. Our results show that the pathways involved in induction of hindbrain serotonergic neurons are likely to be conserved in all vertebrates and help establish the zebrafish as a model system to study this important neuronal class. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 275–288, 2004

We were presented with a technical challenge driven by a clinical need. A patient with proximal femoral focal deficiency required gait analysis, but our typical biomechanical model [Vicon Clinical Manager (VCM)] would not have correctly identified his abnormal right hip center (RHIP). His underdeveloped right femur was fused to his ileum, his anatomical knee functioned as his right hip, and an above-knee prosthesis provided functional knee and ankle joints. During a special calibration, we estimated the global location of RHIP as the center of the femoral epicondyles, also identifying the global location of pelvic markers. These data were used in equations after Davis et al.4to establish local coordinates for RHIP. We used a system of three simultaneous equations to solve for input to VCM that would reproduce this location for RHIP. This procedure allowed for inverse dynamics in VCM, and showed the emergence of an abduction moment at the right hip postoperatively, that exceeded changes predicted by sensitivity analyses. Although our clinical need was met, we concluded that a better approach would have involved full implementation of custom models to reflect abnormal patient anatomy. © 2003 Biomedical Engineering Society. PAC2003: 8719St, 8710+e

VICON Clinical Manager software is widely used for gait analysis and has four methods for computing ankle plantarflexion–dorsiflexion motion and transverse plane ankle rotation profiles. The authors evaluated 14 subjects with a diagnosis of spastic cerebral palsy and tibial torsion ranging from 39° internal torsion to 90° external torsion, using the four different processing methods. It was found that clinically measured tibial torsion >20° external or >15° internal led to significant differences in the calculated ankle plantarflexion–dorsiflexion and transverse plane ankle rotation measurements between the four methods. Pearson correlations indicated that these differences increased with increasing external or internal tibial torsion. The variability was enough to affect conclusions of published articles and clinical decision making.

Zebrafish embryos homozygous for the masterblind (mbl) mutation exhibit a striking phenotype in which the eyes and telencephalon are reduced or absent and diencephalic fates expand to the front of the brain. Here we show that mbl(-/-) embryos carry an amino-acid change at a conserved site in the Wnt pathway scaffolding protein, Axin1. The amino-acid substitution present in the mbl allele abolishes the binding of Axin to Gsk3 and affects Tcf-dependent transcription. Therefore, Gsk3 activity may be decreased in mbl(-/-) embryos and in support of this possibility, overexpression of either wild-type Axin1 or Gsk3beta can restore eye and telencephalic fates to mbl(-/-) embryos. Our data reveal a crucial role for Axin1-dependent inhibition of the Wnt pathway in the early regional subdivision of the anterior neural plate into telencephalic, diencephalic, and eye-forming territories.

Abstract ObjectiveTo determine the clinical features and long term prognosis of infective endocarditis in patients who were not drug addicts. DesignProspective case series. SettingA university hospital that is both a referral and a primary care centre. Patients138 consecutive cases of infective endocarditis diagnosed and treated from January 1987 to March 1997. ResultsMean patient age was 44 (20) years old. 95 patients (69%) had native valve endocarditis and 43 (31%) had prosthetic valve endocarditis. Staphylococci were the causal microorganisms in 34% of cases and streptococci in 33%. Severe complications occurred in 83% of patients and 51% of patients underwent surgery during the active phase (22% was emergency surgery). Inpatient mortality was 21%. During a follow up of 56 (44) months, 10 patients (9%) needed late cardiac surgery and seven (5% of the whole series) died. Overall 10 year survival was 71%. There were no significant differences in survival depending on the type of treatment received during the hospital stay (medical or combined medical–surgical). ConclusionsA high early surgery rate is related to good long term results and does not increase in-hospital mortality. Medical treatment, however, also offers favourable long term results in cases of responsive infective endocarditis where poor prognostic factors are absent.

Two computational procedures, the density functional B3PW91/6-311+G(2df,2pd) and the ab initio CBS-Q, have been used to calculate optimized geometries, energy minima at 0 K and enthalpies and free energies at 298 K for atoms and molecules involved in the ignition and/or combustion of boron. Calculated gas-phase heats of formation are presented for 58 atoms and molecules and are used to find heats of reaction for 83 possible ignition/combustion steps. The most exothermic are found to be BO + F → FBO and BO + O → BO2. It is shown that ΔH (298 K) and ΔH (2000 K) differ, on the average, by only 1.5 kcal/mol; however, ΔG can change quite considerably over the same temperature range. Relative stabilities and equilibrium constants are given for five pairs of isomers. While the geometries were obtained more accurately by the B3PW91 procedure, the CBS-Q is more reliable for heats of formation and heats of reaction.

Summary The cellular and subcellular distribution of 2,4-dinitrophenyl (DNP) groups in the epidermis and regional lymph nodes of the mouse was investigated after epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to sensitized and non-sensitized mice. The peroxidase-antiperoxidase method and the immunogold technique were used to visualize the DNP groups at both light and electron microscopic levels. The highest intensity of immunolabelling was found on tonofilaments of keratinocytes present in the upper layers of the epidermis. On the other hand, in vitro experiments showed that DNFB has the capacity to bind keratin which, together with immunocytochemistry, suggests that this molecule may be one of the skin protein carriers for DNFB. In addition, intense immunostaining for DNP was observed in the Golgi area of some epidermal Langerhans cells. Cells immunoreactive to DNP were also observed in the marginal sinus of cervical lymph nodes 6, 12 and 24 h after challenge. Immunoelectron microscopy revealed immunoreactive DNP groups in phagosomes of Langerhans cells at this site. The present findings support the hypothesis that the hapten DNFB penetrates passively into the cytoplasm of Langerhans cells, concentrates in the Golgi area and, during the migration of Langerhans cells to the lymph nodes, it is probably processed in the lysosomes before its presentation to T lymphocytes.

Twenty-three children who had unilateral surgery for idiopathic clubfeet underwent gait analysis and isokinetic muscle-strength testing at an average of 10 years after surgical release. Ankle sagittal-plane kinematics were disturbed in 20 clubfeet. Fifteen children had an internal foot-progression angle. Genu valgum and knee hyperextension were common. Plantarflexion power was decreased by 23% on the side of surgery (p= 0.00005). Quadriceps weakness (defined as a decrease in strength > 10% of the nonoperated-on limb's strength) was seen in nine of 22 operated-on limbs and hamstring weakness in eight of 22. Gastrocsoleus weakness exceeded 10% in 16 of 21 clubfeet. Average weakness of the gastrocsoleus was 27% (p< 0.05). Ten-year analysis of children treated with clubfoot releases revealed disturbances in ankle motion and strength. Loss of plantarflexion power and gastrocsoleus strength can be predicted by Achilles tendon lengthening. Knee kinematic abnormalities and weakness also were seen. These abnormalities produce functional difficulties in gait and may lead to degenerative changes later.

GC-FID was used to monitor changes over time in palmitic, stearic, arachidic, oleic, linoleic and linoleic acid contents of green beans subjected to various preservation treatments. In beans stored in polyethylene bags at -22°C without prior blanching, all fatty acid contents dropped appreciably within the first month of storage, regardless of whether the beans had been hand- or vacuum-packed. In beans which had been freeze-dried then stored at room temperature in an airtight container, polyunsaturated fatty acid contents dropped appreciably only after 2 months.

To assess the role of 111In antimyosin antibody (AbAm) in the delineation of myocardial damage following coronary bypass surgery, we studied 51 consecutive patients who underwent coronary surgery, 27 of whom had a history of prior myocardial infarction. All patients underwent a diagnostic protocol comprising: (1) 99Tcmpyrophosphate (PYP) and AbAm injection 48 h after surgery (AbAm imaging 24 and 48 h post-injection) (myocardial/background and myocardial/lung ratios were obtained respectively from the computer image); (2) Radioimmunoassay (RIA) serum CK-B levels from samples obtained immediately before surgery, and 24 and 48 h later; (3) clinical and ECG follow-up. Twenty-five patients showed positive AbAm studies, 10 had positive PYP images, and 21 had CK-B levels above normal limits at 24 h. One patient with abnormal AbAm, PYP and CK-B studies had new Q waves on the ECG after surgery. This patient was considered to have sustained a peri-operative myocardial infarction. The large number of positive AbAm studies probably reflects myocardial damage frequently associated with coronary bypass surgery.

A previous baseline cross-sectional comparison of cognitive performance of a group of AIDS-free, HIV-seropositive intravenous drug users with seronegative control intravenous drug users revealed no significant differences attributable to HIV. We now present longitudinal follow-up results from the same cohort of 160 intravenous drug users. There were no differences in performance by serostatus group at either 6- or 12-month follow-up visits, although differences by age and education were observed. Improvement in performance secondary to practice effects was comparable in both serostatus groups. These findings confirm that chronic intravenous drug use may be associated with a wide range of neuropsychological deficits, but there is no evidence that such preexisting deficits interact with HIV infection to produce additional cognitive impairment in otherwise asymptomatic intravenous drug users. Together with results from other high-risk groups such as homosexual/bisexual men and hemophiliacs, these results confirm that neurocognitive abnormalities during the presymptomatic stages of HIV infection are rare, regardless of the route of acquisition of the virus.

We have taken advantage of the optical transparency of zebrafish embryos to investigate the patterns of cell division, movement and shape during early stages of development of the central nervous system. The surface-most epiblast cells of gastrula and neurula stage embryos were imaged and analysed using a computer-based, time-lapse acquisition system attached to a differential interference contrast (DIC) microscope. We find that the onset of gastrulation is accompanied by major changes in cell behaviour. Cells collect into a cohesive sheet, apparently losing independent motility and integrating their behaviour to move coherently over the yolk in a direction that is the result of two influences: towards the vegetal pole in the movements of epiboly and towards the dorsal midline in convergent movements that strengthen throughout gastrulation. Coincidentally, the plane of cell division becomes aligned to the surface plane of the embryo and oriented in the anterior-posterior (AP) direction. These behaviours begin at the blastoderm margin and propagate in a gradient towards the animal pole. Later in gastrulation, cells undergo increasingly mediolateral-directed elongation and autonomous convergence movements towards the dorsal midline leading to an enormous extension of the neural axis. Around the equator and along the dorsal midline of the gastrula, persistent AP orientation of divisions suggests that a common mechanism may be involved but that neither oriented cell movements nor shape can account for this alignment. When the neural plate begins to differentiate, there is a gradual transition in the direction of cell division from AP to the mediolateral circumference (ML). ML divisions occur in both the ventral epidermis and dorsal neural plate. In the neural plate, ML becomes the predominant orientation of division during neural keel and nerve rod stages and, from late neural keel stage, divisions are concentrated at the dorsal midline and generate bilateral progeny (C. Papan and J. A. Campos-Ortega (1994) Roux's Arch. Dev. Biol. 203, 178-186). Coincidentally, cells on the ventral surface also orient their divisions in the ML direction, cleaving perpendicular to the direction in which they are elongated. The ML alignment of epidermal divisions is well correlated with cell shape but ML divisions within the neuroepithelium appear to be better correlated with changes in tissue morphology associated with neurulation.

We determined incidence and future projections of dementia after AIDS onset in 492 homosexual men with AIDS in the Baltimore/Los Angeles sites of the Multicenter AIDS Cohort Study, 64 of whom developed dementia. We studied various risk factors for dementia, including demographic and clinical features, medical history, markers of immune status before AIDS, and zidovudine use. During the first 2 years after AIDS, HIV dementia developed at an annual rate of 7. Overall, 15 of the cohort followed through death developed dementia. The median survival after dementia was 6.0 months. Using a proportional hazards model, risk factors for more rapid development of dementia were lower hemoglobin (relative hazard, 0.59 per additional 2 g/dl;p0.0005) and body mass index (relative hazard, 0.64 per additional 5 kg/m2; p0.05) 1 to 6 months before AIDS, more constitutional symptoms 7 to 12 months before AIDS (relative hazard, 1.68 per additional symptom, p0.005), and older age at AIDS onset (relative hazard, 1.60 per decade older; p0.009). In a multivariate model, pre-AIDS hemoglobin remained the most significant predictor of dementia. There were no significant risks defined from demographic characteristics, specific AIDS-defining illnesses, zidovudine use before AIDS, or CD4 lymphocyte count before AIDS. We project that 12 months after the first AIDS diagnosis, 7.1 of survivors will have dementia. The observed association between anemia, low weight, constitutional symptoms, and dementia suggests a role for cytokines inducing both systemic and neurologic disease.

HPLC (using a C18 column, water at pH 2·2 as mobile phase, and UV detection) was used to monitor the vitamin C content of deep-frozen (-22°C) green beans and Padrón peppers over 12 months. Unblanched beans and peppers lost 97% of their vitamin C within 1 month of freezing, whether or not they were contained in bags sealed under vacuum. Blanching reduced the beans’ vitamin C content by 28%, but limited further decreases to between 3 (vacuum sealed) and 10% (no vacuum) in 12 months. These results confirm the utility of blanching in the preservation of vegetables by deep-freezing. © 1998 SCI.

Limited data are available on cognitive performance in populations of intravenous drug users during the early, asymptomatic stages of human immunodeficiency virus type 1 (HIV-1) infection. Between 1988 and 1990, 151 participants from the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, were evaluated neuropsychologically on a semiannual basis. This analysis focused on whether history of substance abuse influenced neuropsychological test performance. At baseline, 102 participants were HIV-1-seropositives who were free of acquired immunodeficiency syndrome and 49 participants were seronegative. Multivariate analyses, adjusting for correlation of repeated outcome measures, were conducted to determine predictors of neuropsychological functioning. Effects of the frequency of reported past use of marijuana, heroin, cocaine, barbiturates, and alcohol were not statistically associated with performance on the tests. Age and education were the most important predictors of test performance, and a significant practice effect was observed for most measures. After adjustment for age, education, the practice effect, and frequency of drug use, neuropsychological performance over time did not vary by HIV-1 serostatus. Overall, after acutely intoxicated individuals were excluded, neither frequency of drug and alcohol use nor HIV-1 seropositivity significantly influenced neuropsychological test performance over a 1-year period.

Structures and energies have been computed for six azines, their mononitro derivatives, and the radicals formed by loss of a hydrogen or a nitro group. A density functional procedure (B3P86/6-31+G**) was used. Relative stabilities within isomeric groups are compared, and 20 C−H and C−NO2 dissociation energies are presented. The results are viewed as demonstrating the importance of the electron-attracting powers of the ring nitrogens.