First Measurement of Near-Threshold J/ψ Exclusive Photoproduction off the Proton.

We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).

Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease of unknown etiology with only two federally approved drug options. Given the complex molecular pathogenesis of IPF involving multiple cell types and multiple pathways, we explore the effects of a potential antifibrotic and antioxidant drug combination. Curcumin is a polyphenolic compound derived from turmeric with significant biological activity including a potential antifibrotic capacity. N-acetylcysteine (NAC) is a precursor to the antioxidant glutathione. To advance our understanding of these molecules, and to identify a clinical application, we present a small number of focused experiments that interrogates the effect of curcumin and NAC on pathways relevant to IPF in both fibroblasts and epithelial cells. METHODS: Primary epithelial cell and fibroblasts isolated from patients with IPF were challenged with a combination treatment of NAC and curcumin. Evaluation of the antifibrotic potential and effect on oxidative stress was performed through QPCR gene expression analysis and functional assays including scratch tests, viability assays, and measurement of induced reactive oxygen species. RESULTS: We demonstrate that curcumin alone does have antifibrotic potential, but that effect is accompanied by proapoptotic increases in oxidative stress. Coupled with this, we find that NAC alone can reduce oxidative stress, but that epithelial cell viability is decreased through this treatment. However, co-administration of these two molecules decreases oxidative stress and maintains high cell viability in both cell types. In addition, this co-treatment maintains an antifibrotic potential. CONCLUSIONS: These findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.

Evaluation of the robustness of polarization attraction for 10.7-GBaud NRZ-BPSK after long-haul 100-GHz DWDM transmission.

An investigation was carried out on the polarization attraction (PA) of a polarization-scrambled 10.7-GBaud NRZ-BPSK signal in a 1-km-long highly nonlinear fiber (HNLF). For the back-to-back case, PA on an ASE-loaded signal yielded a receiver sensitivity penalty of ≈ 14.5 dB at the ITU-T G.975.1.I3 FEC threshold of 3.5 × 10-3, relative to matched-filter reception theory. After long-haul 100-GHz DWDM transmission in a recirculating loop, PA on the output signal was found to achieve approximately the same receiver sensitivity performance, as that of the back-to-back case. From these experiments, it is concluded that the Gordon-Mollenauer effect due to propagation in the HNLF during PA dominates other impairments including those arising from the long-haul 100-GHz DWDM recirculating loop transmission.

"Joven & Fuerte": Program for Young Women with Breast Cancer in Mexico - Initial Results.

Despite the high rates of breast cancer among young Mexican women, their special needs and concerns have not been systematically addressed. To fulfill these unsatisfied demands, we have developed "Joven & Fuerte: Program for Young Women with Breast Cancer in Mexico," the first program dedicated to the care of young breast cancer patients in Latin America, which is taking place at the National Cancer Institute of Mexico and the two medical facilities of the Instituto Tecnológico y de Estudios Superiores de Monterrey. The program was created to optimize the complex clinical and psychosocial care of these patients, enhance education regarding their special needs, and promote targeted research, as well as to replicate this program model in other healthcare centers across Mexico and Latin America. From November 2013 to February 2017, the implementation of the "Joven & Fuerte" program has delivered specialized care to 265 patients, through the systematic identification of their particular needs and the provision of fertility, genetic, and psychological supportive services. Patients and families have engaged in pedagogic activities and workshops and have created a motivated and empowered community. The program developed and adapted the first educational resources in Spanish dedicated for young Mexican patients, as well as material for healthcare providers. As for research, a prospective cohort of young breast cancer patients was established to characterize clinicopathological features and psychosocial effects at baseline and during follow-up, as a guide for the development of specific cultural interventions addressing this vulnerable group. Eventually, it is intended that the program's organization and structure can reach national and international interactions and serve as a platform for other countries.

Polarization-insensitive all-optical dual pump-phase transmultiplexing from 2 × 10-GBd OOKs to 10-GBd RZ-QPSK using cross-phase modulation in a birefringent nonlinear PCF.

Polarization-insensitive (PI) all-optical dual pump-phase transmultiplexing from 2 × 10-GBd OOKs to 10-GBd RZ-QPSK was successfully demonstrated in a birefringent nonlinear photonic crystal fiber (PCF), by utilizing cross-phase modulation (XPM) and the inherent birefringence of the device, for the first time. PI operation was achieved by launching the probe and one pump off-axis while the state of polarization (SOP) of the other pump was randomized. Optimum pump-probe detuning, all within the C-Band, was also utilized to reduce the polarization-induced power fluctuation. Receiver sensitivity penalty at 10-9 bit-error-rate was < 5.5 dB in PI operation, relative to the FPGA-precoded RZ-DQPSK baseline.

All-optical amplitude-phase transmultiplexing of RZ-OOK and RZ-BPSK to RZ-QPSK by polarization-insensitive XPM using a nonlinear birefringent AlGaAs waveguide.

Polarization-insensitive (PI) phase-transmultiplexing (PTM) of a 10-Gb/s return-to-zero ON-OFF keying (RZ-OOK) pump and a 10-Gb/s RZbinary phase-shift keying (RZ-BPSK) probe to 20-Gb/s RZ-quadrature-PSK (RZ-QPSK) has been successfully demonstrated for the first time in a passive, birefringent AlGaAs waveguide, utilizing PI cross-phase modulation (PI-XPM). For differential QPSK (DQPSK)-detection, a 10 − 9-BER pre-amplified receiver sensitivity penalty of ≈ 2.5 dB for the in-phase component and ≈ 4.9 dB for the quadrature component were found. The penalties were relative to the FPGA-precoded RZ-DQPSK baseline for a pump-probe detuning of ≈ 12 nm, when the probe state of polarization was scrambled and the pump was launched off-axis into the waveguide.

Functions of S100 proteins.

The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.

Cautious observation or blanket scanning? An investigation into paediatric attendances to an emergency department after head injury.

In September 2007, the National Institute for Health and Clinical Excellence (NICE) in the UK issued a newly updated guideline (CG56) on the early care of adults and children with head injuries.(8) The guideline gives some new recommendations, in particular with regards to imaging of children with head injury. We undertook a study to investigate the management of children presenting with head injury to our emergency department and to assess their outcomes and the CT scanning rate. We then retrospectively applied the new NICE guidelines, using information documented in the case notes, to establish whether adherence to the guidelines would significantly affect CT scanning rates. 237 paediatric head injury cases were seen over the 2-month period that was studied. The actual CT scanning rate observed was 2.1%, rising to 18.1% after strictly applying NICE criteria. This increased scanning rate raises some important issues with regards to patient safety and service provision.

Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans).

Only with the development of the uncoupling protein 1 (UCP1)-ablated mouse has it become possible to strictly delineate the physiological significance of the thermogenic capacity of brown adipose tissue. Considering the presence of active brown adipose tissue in adult humans, these insights may have direct human implications. In addition to classical nonshivering thermogenesis, all adaptive adrenergic thermogeneses, including diet-induced thermogenesis, is fully dependent on brown adipocyte activity. Any weight-reducing effect of ß(3)-adrenergic agonists is fully dependent on UCP1 activity, as is any weight-reducing effect of leptin (in excess of its effect on reduction of food intake). Consequently, in the absence of the thermogenic activity of brown adipose tissue, obesity develops spontaneously. The ability of brown adipose tissue to contribute to glucose disposal is also mainly related to thermogenic activity. However, basal metabolic rate, cold-induced thermogenesis, acute cold tolerance, fevers, nonadaptive adrenergic thermogenesis and processes such as angiogenesis in brown adipose tissue itself are not dependent on UCP1 activity. Whereas it is likely that these conclusions are also qualitatively valid for adult humans, the quantitative significance of brown adipose tissue for human metabolism--and the metabolic consequences for a single individual possessing more or less brown adipose tissue--awaits clarification.

Nitric oxide in the evaluation of congenital heart disease with pulmonary hypertension: factors related to nitric oxide response.

Inhaled nitric oxide (NO) has been used in the preoperative evaluation of patients with congenital heart disease and pulmonary hypertension. The purpose of this study was to characterize responses in pulmonary vascular resistance (PVR) to oxygen and increasing doses of NO during cardiac catheterization and to determine if any related factors affect the response of the pulmonary vascular bed to NO. A prospective analysis of 42 patients (median age, 3.0 years) with congenital heart disease and pulmonary hypertension who underwent NO testing was performed. Systemic vascular resistance (SVR) and PVR were assessed in room air, 100% oxygen, and oxygen plus 20, 40, and 80 parts per million (ppm) NO. Changes in pulmonary artery pressure, PVR, and SVR were assessed. The response to NO was then correlated to individual patient's age, gender, type of heart defect, the presence of trisomy 21, and baseline PVR/SVR. There was a greater decrease in PVR and PVR/SVR with 20 ppm NO than with oxygen alone. There was no additional decrease at 40 or 80 ppm NO. There was no correlation between age, gender, type of congenital heart disease, and baseline PVR/SVR ratio with the degree of response to NO. Patients with trisomy 21 had less of a response to NO (p = 0.017) than patients without trisomy 21. There is no difference in determining PVR response with doses of NO beyond 20 ppm during cardiac catheterization. Age, gender, and baseline PVR/SVR ratio are not associated with responsiveness to NO. Patients with trisomy 21 may be less responsive to NO.

Beta-adrenoceptors, but not alpha-adrenoceptors, stimulate AMP-activated protein kinase in brown adipocytes independently of uncoupling protein-1.

AIMS/HYPOTHESIS: Brown adipocytes provide a potentially important model system for understanding AMP-activated protein kinase (AMPK) regulation, where adrenergic stimulation leads to mitochondrial uncoupling through uncoupling protein-1 (UCP1) activity. AMPK is a sensor of energy homeostasis and has been implicated in glucose and lipid metabolism in several insulin-sensitive tissues. The aim of this study was to characterise the potential role of AMPK in adrenergically mediated glucose uptake and to find out whether UCP1 is involved in the adrenergic activation of AMPK. METHODS: We used primary brown adipocytes differentiated in culture and measured AMPK phosphorylation and glucose uptake following adrenergic activation. RESULTS: Treatment of adipocytes with noradrenaline (norepinephrine) caused phosphorylation of AMPK via beta-adrenoceptors and not alpha(1)- or alpha(2)-adrenoceptors. This effect was not beta(3)-adrenoceptor specific, since responses remained intact in adipocytes from beta(3)-adrenoceptor knock-out mice. These effects were also mimicked by forskolin and cAMP analogues. Treatment of cells with adenine 8-beta-D-arabinofuranoside, an AMPK inhibitor, partially blocked beta-adrenoceptor-mediated increases in glucose uptake. Brown adipocytes are characterised by the production of UCP1, which can uncouple the mitochondria. Using adipocytes from Ucp1(+/+) and Ucp1(-/-) mice, we showed that noradrenaline-mediated phosphorylation of AMPK does not require the presence or activity of UCP1. CONCLUSIONS/INTERPRETATION: These results suggest a pathway where increases in cAMP mediated by beta-adrenoceptors leads to activation of AMPK in brown adipocytes, which contributes in part to beta-adrenoceptor-mediated increases in glucose uptake, an effect independent of the presence or function of UCP1.

Oral versus written administration of the Geriatric Depression Scale.

Forty-four female nursing home residents completed the Geriatric Depression Scale (GDS) twice, using both oral and written administration formats. Presentation was counterbalanced. The Mini-Mental State Exam and the Mattis Dementia Rating Scale were administered to each participant between the GDS administrations. All testing was completed within one session. Test-retest reliability analysis revealed a significant correlation between oral and written administrations for higher cognitive functioning participants, but no correlation for impaired participants. Therefore, the use of the GDS in a cognitively impaired elderly population is questioned. Additionally, oral versus written administration formats were found to be not equivalent in the higher functioning group.

Life without UCP1: mitochondrial, cellular and organismal characteristics of the UCP1-ablated mice.

Mice devoid of the original uncoupling protein UCP1 have provided opportunities to delineate UCP1 function in a series of biochemical and physiological contexts. The isolated brown-fat mitochondria from such mice are fully coupled (without the addition of GDP), but still exhibit a depressed capacity for ATP synthesis. However, they only show a 2-fold decrease in sensitivity to the de-energizing effect of free fatty acids, compared with UCP1-containing mitochondria, whereas they possess a (UCP1-independent) 50-fold higher sensitivity than liver mitochondria; the fatty acid sensitivities in wild-type and UCP1-deficient mitochondria may, however, be of different natures. Despite the fact that brown-fat cells from UCP1-ablated mice cannot produce heat when stimulated by noradrenaline ('norepinephrine') or fatty acids, UCP1-ablated mice can be induced to tolerate extended cold exposure, but the heat then fully results from shivering thermogenesis. Recruitable or adaptive (by cold acclimation or adaptation to a cafeteria diet) adrenergically-stimulated thermogenesis does not exist in the UCP1-ablated animals, demonstrating the unique ability of UCP1 to mediate recruitable non-shivering thermogenesis. In addition to information on the function of UCP1, the UCP1-ablated mice can be used to gain information concerning the function of the UCP1 homologues. Thus whereas an uncoupling function of the UCP1 homologues cannot be excluded, UCP1-ablated animals clearly lack any ability to recruit any UCP1 homologue to functionally replace the loss of thermogenesis resulting from UCP1. UCP1 (thermogenin) thus remains the only protein the activity of which can be recruited for the purpose of facultative thermogenesis.

Assessment instruments used in the education and treatment of persons with autism: brief report of a survey of national service centers.

Although assessment is a critical component in the education and treatment of persons who have autism, there is insufficient information about the types of assessment instruments that are used routinely by practitioners. This brief report describes a survey of national service centers to determine their use of standardized instruments and the purposes of their assessment practices. Data from centers representing 30 states revealed that (a) the number of assessment instruments endorsed by centers increased as centers adopted a "multidisciplinary" approach to education and treatment, (b) the largest proportion of instruments fell within intellectual, motor, and language/communication domains, and (c) instruments were used most frequently for diagnostic and curriculum design purposes. Agreement among practitioners on the selection of instruments occurred most frequently in the domains of projective, adaptive behavior, and family assessment. The implications from these findings for assessment practices in autism are discussed.

Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold.

Adaptive nonshivering thermogenesis may have profound effects on energy balance and is therefore therefore is a potential mechanism for counteracting the development of obesity. The molecular basis for adaptive nonshivering thermogenesis has remained a challenge that sparked acute interest with the identification of proteins (UCP2, UCP3, etc.) with high-sequence similarity to the original uncoupling protein-1 (UCP1), which is localized only in brown adipose tissue. Using UCP1-ablated mice, we examined whether any adaptive nonshivering thermogenesis could be recruited by acclimation to cold. Remarkably, by successive acclimation, the UCP1-ablated mice could be made to subsist for several weeks at 4C during which they had to constantly produce heat at four times their resting levels. Despite these extreme requirements for adaptive nonshivering thermogenesis, however, no substitution of shivering by any adaptive nonshivering thermogenic process occurred. Thus, although the existence of, for example, muscular mechanisms for adaptive nonshivering thermogenesis has recurrently been implied, we did not find any indication of such thermogenesis. Not even during prolonged and enhanced demand for extra heat production was any endogenous hormone or neurotransmitter able to recruit any UCP1-independent adaptive nonshivering thermogenic process in muscle or in any other organ, and no proteins other than UCP1-not even UCP2 or UCP3-therefore have the ability to mediate adaptive nonshivering thermogenesis in the cold.

Arotinolol is a weak partial agonist on beta 3-adrenergic receptors in brown adipocytes.

Arotinolol, a clinically used alpha/beta-adrenergic blocker, has been demonstrated to be an anti-obesity agent. The anti-obesity effect of arotinolol was suggested to be the result of direct activation of thermogenesis in brown-fat cells. We tested the ability of arotinolol to stimulate thermogenesis (oxygen consumption) in isolated brown-fat cells and in intact animals. Arotinolol stimulated thermogenesis in brown-fat cells isolated from mouse and hamster. A relatively low sensitivity to the beta-adrenergic antagonist propranolol (pK(B) approximately 6) indicated that arotinolol interacted with the beta3-adrenergic receptor. On the beta3-receptor, arotinolol was a very weak (EC50 approximately 20 microM) and only partial (approximately 50%) agonist, but arotinolol also demonstrated the properties of being a beta3-receptor antagonist with a pK(B) of 5.7. In intact animals, only the antagonistic action of arotinolol could be observed. Because arotinolol is only a very weak and partial agonist on the beta3-receptors, direct stimulation of thermogenesis in brown adipose tissue is unlikely to be sufficient to cause significant weight loss. It may be necessary to invoke additional pathways to explain the anti-obesity effects of chronic treatment with arotinolol.

Corneal virulence of LasA protease--deficient Pseudomonas aeruginosa PAO1.

PURPOSE: Pseudomonas aeruginosa PAO1 deficient in LasA protease was reported to be ocularly avirulent. However, the avirulence of this mutant could not attributed to the loss of LasA protease. The purpose of this study was to define the mechanism for such a mutant's inability to cause corneal disease. METHODS: A LasA protease--deficient mutant of P. aeruginosa PAO1 was constructed by allelic exchange. Virulence of this mutant in mouse and rabbit models of keratitis was assessed by scoring for ocular disease and quantitating viable bacteria from infected corneas. Adherence to scarified mouse corneal tissue was determined with an organ culture assay. RESULTS: In the mouse eye, the LasA protease--deficient mutant was not virulent, despite being as adherent as its parent strain. Virulence of the mutant was also significantly reduced in the rabbit eye. Complementation with lasA did not restore virulence in either model of infection. Neither the mutant nor the mutant complemented with lasA grew well in ocular tissue. An analysis of the mutant showed that it was auxotrophic for leucine. CONCLUSION: These data show that the mutant's avirulence in the eye is caused by poor growth in the ocular environment and not the loss of a functional lasA gene.

Gallstones and laparoscopic cholecystectomy in hepatitis C patients.

Our aims were to determine the incidence of gallstones in a cohort of patients infected with hepatitis C for 20 years, and to analyse the outcome of all patients infected with hepatitis C undergoing laparoscopic cholecystectomy. A hepatitis C screening programme in place in Ireland since 1994 identified 965 patients with hepatitis C antibodies out of 62,667 patients screened. The hepatology unit of Cork University Hospital has 318 patients with hepatitis C. Of patients identified by screening, 201 were post partum women infected via contaminated Anti-D immunoglobulin administered in 1977. Thirty-five (17.4%) of two hundred and one patients with hepatitis C since 1977 had developed gallstones after twenty years. A total of 34 patients with hepatitis C underwent laparoscopic cholecystectomy. One patient required conversion to open cholecystectomy. There were no complications and no mortality. There was a low rate of cirrhosis (11%) on examining liver histology. The incidence of gallstones in a cohort of patients infected with hepatitis C for twenty years approximates to that of the general population. The low rate of cirrhosis in this group may be related to a low consumption of alcohol. Laparoscopic cholecystectomy is a safe procedure in patients with mild chronic liver disease caused by hepatitis C.

Pseudomonas aeruginosa LasA protease and corneal infections.

PURPOSE: A mutant strain of Pseudomonas aeruginosa deficient in LasA protease (staphylolytic protease) has been described as having reduced ocular virulence, suggesting that LasA is a major virulence factor. This study was undertaken to provide further genetic analysis of the role of P. aeruginosa LasA protease in ocular infections. METHODS: LasA protease-deficient mutants of P. aeruginosa PAO1-V and ATCC 19660 were constructed by allelic replacement. Mutants and their respective wild type parent strains were evaluated for virulence and growth in the eye using mouse scarification and rabbit intrastromal injection models of keratitis. RESULTS: LasA protease-deficient mutants of both strains were as virulent as wild type strains, growing to 4 to 6 log10 CFU/cornea and causing significant ocular pathology in the mouse (P > 0.42) and rabbit (P > 0.53). CONCLUSIONS: These data show that LasA protease is not a major corneal virulence factor, suggesting that the main mechanism of corneal damage has yet to be definitively identified.

Use of tissue plasminogen activator in a stroke after radiofrequency ablation of a left-sided accessory pathway.

We describe the case of a 12-year-old girl who had a thromboembolic stroke after radiofrequency ablation of a left posterior accessory pathway involving a transseptal procedure. Symptoms of a stroke occurred 7 hours 15 minutes after completion of the procedure. Tissue plasminogen activator (tPA) was given 2 hours 30 minutes after the onset of symptoms, with complete resolution of her neurologic symptoms. No adverse effects from the tPA were seen. Because of the late onset of symptoms in this case, overnight in-hospital observation is warranted for patients who undergo radiofrequency ablation of a left-sided accessory pathway or an accessory pathway in a patient with the ability to shunt right to left. In this case, tPA was an effective and safe drug to use following a cerebral thromboembolic event occurring after a cardiac catheterization procedure.