Deeply Virtual Compton Scattering Cross Section at High Bjorken x_{B}.

We report high-precision measurements of the deeply virtual Compton scattering (DVCS) cross section at high values of the Bjorken variable x_{B}. DVCS is sensitive to the generalized parton distributions of the nucleon, which provide a three-dimensional description of its internal constituents. Using the exact analytic expression of the DVCS cross section for all possible polarization states of the initial and final electron and nucleon, and final state photon, we present the first experimental extraction of all four helicity-conserving Compton form factors (CFFs) of the nucleon as a function of x_{B}, while systematically including helicity flip amplitudes. In particular, the high accuracy of the present data demonstrates sensitivity to some very poorly known CFFs.

Form Factors and Two-Photon Exchange in High-Energy Elastic Electron-Proton Scattering.

We present new precision measurements of the elastic electron-proton scattering cross section for momentum transfer (Q^{2}) up to 15.75 (GeV/c)^{2}. Combined with existing data, these provide an improved extraction of the proton magnetic form factor at high Q^{2} and double the range over which a longitudinal or transverse separation of the cross section can be performed. The difference between our results and polarization data agrees with that observed at lower Q^{2} and attributed to hard two-photon exchange (TPE) effects, extending to 8 (GeV/c)^{2} the range of Q^{2} for which a discrepancy is established at >95% confidence. We use the discrepancy to quantify the size of TPE contributions needed to explain the cross section at high Q^{2}.

Deep Exclusive Electroproduction of π

We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of x_{B} (0.36, 0.48, and 0.60) and Q^{2} (3.1 to 8.4 GeV^{2}) obtained from Jefferson Lab Hall A experiment E12-06-014. The corresponding structure functions dσ_{T}/dt+εdσ_{L}/dt, dσ_{TT}/dt, dσ_{LT}/dt, and dσ_{LT^{'}}/dt are extracted as a function of the proton momentum transfer t-t_{min}. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross section throughout this kinematic range. The data are well described by calculations based on transversity generalized parton distributions coupled to a helicity flip distribution amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.

Interrelationship between late gestational ewe factor and early life lamb factors in semi-arid tropical region.

The limitation in feed availability in the semi-arid region during the lean period can result in a variation of the body condition, body weight of pregnant ewe which in turn may affect the lamb birth weight, colostrum immunoglobulin, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Therefore, the present study was initiated to assess the interrelationship between late gestational ewe factor and early life lamb factors in the semi-arid tropical region. For this purpose, 83 Malpura and 45 Avikaline pregnant ewes were selected and their body condition score (BCS) at late gestation, body weight at lambing, and birth weight of lambs was recorded. The BCS of ewes in late gestation had significant (P < 0.001) positive correlation (r2 = 0.465) with the birth weight of lambs. The body weight at lambing was significantly (P < 0.05) higher in single-lamber ewes as compared to twin-bearing ewes. The plasma IGF-1 of lamb increased significantly (P < 0.05) with the increase of BCS of ewe at the late gestation as well as body weight after lambing. The colostrum of twin-lamb producing ewes had higher (P < 0.05) IgG content than single-lamb producing ewes. The concentration of IGF-1 was significantly (P < 0.05) higher in single-born lamb as compared to twin-born lamb. Based on the results of the present study, it is to conclude that higher BCS at late gestation and higher body weight of ewes at lambing is desirable for producing lambs with a higher birth weight having higher growth potential as well as chances of survival.

Dynamic response mitigation of floating wind turbine platforms using tuned liquid column dampers.

In this paper, we experimentally study and compare the effects of three combinations of multiple tuned liquid column dampers (MTLCDs) on the dynamic performance of a model floating tension-leg platform (TLP) structure in a wave basin. The structural stability and safety of the floating structure during operation and maintenance is of concern for the performance of a renewable energy device that it might be supporting. The dynamic responses of the structure should thus be limited for these renewable energy devices to perform as intended. This issue is particularly important during the operation of a TLP in extreme weather conditions. Tuned liquid column dampers (TLCDs) can use the power of sloshing water to reduce surge motions of a floating TLP exposed to wind and waves. This paper demonstrates the potential of MTLCDs in reducing dynamic responses of a scaled TLP model through an experimental study. The potential of using output-only statistical markers for monitoring changes in structural conditions is also investigated through the application of a delay vector variance (DVV) marker for different conditions of control for the experiments.

Microvascular breast reconstruction and thromboembolic events in patients on hormone therapy: Audit of practice from a tertiary referral centre.

INTRODUCTION: Hormonal therapy with tamoxifen and aromatase inhibitors reduces breast cancer recurrence and mortality but represents a risk factor for thromboembolic events. Therefore, most surgeons discontinue hormonal agents before microvascular surgery and for a variable period thereafter. There are no guidelines regarding when therapy should be stopped (preoperatively) or when it should be resumed (post-operatively). We, therefore, audited our hospital practice with the objective of making recommendations for microvascular breast reconstruction patients. PATIENTS AND METHODS: A review was performed of all free flap breast reconstructions between 2014 and 2019. Patients were classified according to hormone medication status at operation. Timings of drug cessation and recommencement were recorded. Thrombotic events, namely flap microvascular thrombosis, deep vein thrombosis, superficial vein thrombosis and pulmonary embolism, were compared. RESULTS: A total of 240 patients had 275 free flaps over five years with 36 receiving hormone therapy within one month prior to surgery, which was discontinued 8.5 days (range: 0-28 days) before surgery. Intraoperative microvascular thromboses (HT 2.0%, NHT 0%, and p = 0.869) and post-operative microvascular complications/flap re-explorations (HT 6.6%, NHT 0%, and p = 0.234) were comparable between the two groups. Systemic venous thromboembolic events were also similar (HT 8.3%, NHT 6.1%, and p = 0.893). Age, BMI, smoking status and preoperative chemotherapy did not influence the incidence of thrombotic complications. CONCLUSION: Hormone therapy did not significantly increase the risk of thromboembolic events. Despite the widespread practice of withholding it for 2 weeks prior to reconstructive surgery, this study does not support such practice being beneficial in terms of thromboembolic events and flap viability. Large-scale trials are needed to establish definitive protocols.

Total Lip Reconstruction after Excision of Cancer with Composite Radial Forearm Palmaris Longus Tendon Free Flap.

Reconstruction of total lip is a challenging task for a plastic surgeon. It becomes more complicated when there is loss of additional tissues like angle of mouth, buccal mucosa or floor of the mouth. Radial forearm flap with palmaris longus tendon provides an easier but reliable technique for three dimensional lip reconstructions with good functional and aesthetic outcome. In this short observational series we included 5 patients of total lip reconstruction and conducted at Sylhet MAG Osmani Medical College Hospital and Private Clinic of Sylhet, Bangladesh from January 2014 to December 2017. Among these one was a case of basal cell carcinoma of upper lip and rest was squamous cell carcinoma of lower lip. The mean age was 71 years. All the flaps survived and patients had normal speech and oral continence. Composite radial forearm flap with palmaris longus tendon is a good, reliable option for total lip reconstruction.

Expression of genes related to oxidative stress in the mouse brain after exposure to silver-25 nanoparticles.

Nanoparticles are small scale substances (<100 nm) used in biomedical applications, electronics, and energy production. Increased exposure to nanoparticles being produced in large-scale industry facilities elicits concerns for the toxicity of certain classes of nanoparticles. This study evaluated the effects of silver-25 nm (Ag-25) nanoparticles on gene expression in different regions of the mouse brain. Adult-male C57BL/6N mice were administered (i.p.) 100mg/kg, 500 mg/kg or 1,000 mg/kg Ag-25 and sacrificed after 24h. Regions from the brain were rapidly removed and dissected into caudate nucleus, frontal cortex and hippocampus. Total RNA was isolated from each of the three brain regions collected and real-time RT-PCR analysis was performed using Mouse Oxidative Stress and Antioxidant Defense Arrays. Array data revealed the expression of genes varied in the caudate nucleus, frontal cortex and hippocampus of mice when treated with Ag-25. The data suggest that Ag-25 nanoparticles may produce neurotoxicity by generating free radical-induced oxidative stress and by altering gene expression, producing apoptosis and neurotoxicity.

The effects of L-carnitine on the combination of, inhalation anesthetic-induced developmental, neuronal apoptosis in the rat frontal cortex.

The anesthetic gas nitrous oxide (N2O) and the volatile anesthetic isoflurane (ISO) are commonly used in surgical procedures for human infants and in veterinary and laboratory animal practice to produce loss of consciousness and analgesia. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA) glutamate receptors or potentiate GABA(A) receptors can trigger widespread apoptotic neurodegeneration. In the present study, the question arises whether a relatively low dose of ISO alone or its combination with N2O entails significant risk of inducing enhanced apoptosis. In addition, the role of L-carnitine to attenuate these effects was also examined. Postnatal day 7 (PND-7) rat pups were exposed to N2O (75%) or a low dose of ISO (0.55%) alone, or N2O plus ISO for 2, 4, 6 or 8 h with or without L-carnitine. The neurotoxic effects were evaluated 6 h after completion of anesthetic administration. No significant neurotoxic effects were observed for the animals exposed to N2O or ISO alone. However, enhanced apoptotic cell death was apparent when N2O was combined with ISO at exposure durations of 6 h or more. Co-administration of L-carnitine (300 or 500 mg/kg, i.p.) effectively protected neurons from the anesthetic-induced damage. These data indicate that 6 h or more of inhaled anesthetic exposure consisting of a combination of N2O and ISO results in enhanced neuronal apoptosis, and L-carnitine effectively blocks the neuronal apoptosis caused by inhalation anesthetics in the developing rat brain.

Anterior cervical fusion using the IntExt combined cage/plate.

PURPOSE: To review our first 30 patients who underwent anterior cervical fusion using IntExt and xenograft. METHODS: Records of 23 men and 7 women aged 18 to 83 (mean, 40) years were reviewed by a single researcher. 23 patients had traumatic fracture-dislocations and 7 had degenerative disease. Pain, range of movement, neurological status, return-to-work status, kyphosis, and lordosis were recorded. Radiography and computed tomography were used to assess integration of the xenograft with the host bone, intervertebral fusion around the cage, and any screw loosening. RESULTS: The mean follow-up duration of the 30 patients was 14 (range, 1-47) months. There was no evidence of screw loosening or breakage. 20 of the 28 patients had no neck pain. Radiographs and/or computed tomographic scans of 23 patients showed bone union or clinical evidence of stability. CONCLUSION: The IntExt is effective in stabilising traumatic fractures. Although the literature does not support single-level plating in degenerative fractures (because of high success rates with autologous bone grafting), the IntExt has advantages of avoiding grafting complications, donor-site morbidity, and resorting to a postoperative collar.

L-carnitine protects neurons from 1-methyl-4-phenylpyridinium-induced neuronal apoptosis in rat forebrain culture.

1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with an elevation of intracellular reactive oxygen species (ROS) and apoptosis. L-carnitine plays an integral role in attenuating the brain injury associated with mitochondrial neurodegenerative disorders. The present study investigates the effects of L-carnitine against the toxicity of MPP+ in rat forebrain primary cultures. Cells in culture were treated for 24 h with 100, 250, 500 and 1000 microM MPP+ alone or co-incubated with L-carnitine. MPP+ produced a dose-related increase in DNA fragmentation as measured by cell death ELISA (enzyme-linked immunosorbent assay), an increase in the number of TUNEL (terminal dUTP nick-end labeling)-positive cells and a reduction in the mitochondrial metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). No significant effect was observed with the release of lactate dehydrogenase (LDH), indicating that cell death presumably occurred via apoptotic mechanisms. Co-incubation of MPP+ with L-carnitine significantly reduced MPP+-induced apoptosis. Western blot analyses showed that neurotoxic concentrations of MPP+ decreased the ratio of BCL-X(L) to Bax and decreased the protein levels of polysialic acid neural cell adhesion molecules (PSA-NCAM), a neuron specific marker. L-carnitine blocked these effects of MPP+ suggesting its potential therapeutic utility in degenerative disorders such as Parkinson's disease, Alzheimer's disease, ornithine transcarbamylase deficiency and other mitochondrial diseases.

Augmented behavioral response and enhanced synaptosomal calcium transport induced by repeated cocaine administration are decreased by calcium channel blockers.

Recent studies suggest that calcium influx via L-type calcium channels is necessary for psychostimulant-induced behavioral sensitization. In addition, chronic amphetamine upregulates subtype Cav1.2-containing L-type calcium channels. In the present studies, we assessed the effect of calcium channel blockers (CCBs) on cocaine-induced behavioral sensitization and determined whether the functional activity of L-type calcium channels is altered after repeated cocaine administration. Rats were administered daily intraperitoneal injections of either flunarizine (40 mg/kg), diltiazem (40 mg/kg) or cocaine (20 mg/kg) and the combination of the CCBs and cocaine for 30 days. Motor activities were monitored on Day 1, and every 6th day during the 30-day treatment period. Daily cocaine administration produced increased locomotor activity. Maximal augmentation of behavioral response to repeated cocaine administration was observed on Day 18. Flunarizine pretreatment abolished the augmented behavioral response to repeated cocaine administration while diltiazem was less effective. Measurement of tissue monoamine levels on Day 18 revealed cocaine-induced increases in DA and 5-HT in the nucleus accumbens. By contrast to behavioral response, diltiazem was more effective in attenuating increases in monoamine levels than flunarizine. Cocaine administration for 18 days produced increases in calcium uptake in synaptosomes prepared from the nucleus accumbens and frontal cortex. Increases in calcium uptake were abolished by flunarizine and diltiazem pretreatment. Taken together, the augmented cocaine-induced behavioral response on Day 18 may be due to increased calcium uptake in the nucleus accumbens leading to increased dopamine (DA) and serotonin (5-HT) release. Flunarizine and diltiazem attenuated the behavioral response by decreasing calcium uptake and decreasing neurochemical release.

Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III).

Oxidative/nitrosative stress is involved in NMDA receptor-mediated excitotoxic brain damage produced by the glutamate analog quinolinic acid. The purpose of this work was to study a possible role of peroxynitrite, a reactive oxygen/nitrogen species, in the course of excitotoxic events evoked by quinolinic acid in the brain. The effects of Fe(TPPS) (5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III)), an iron porphyrinate and putative peroxynitrite decomposition catalyst, were tested on lipid peroxidation and mitochondrial function in brain synaptic vesicles exposed to quinolinic acid, as well as on peroxynitrite formation, nitric oxide synthase and superoxide dismutase activities, lipid peroxidation, caspase-3-like activation, DNA fragmentation, and GABA levels in striatal tissue from rats lesioned by quinolinic acid. Circling behavior was also evaluated. Increasing concentrations of Fe(TPPS) reduced lipid peroxidation and mitochondrial dysfunction induced by quinolinic acid (100 microM) in synaptic vesicles in a concentration-dependent manner (10-800 microM). In addition, Fe(TPPS) (10 mg/kg, i.p.) administered 2 h before the striatal lesions, prevented the formation of peroxynitrite, the increased nitric oxide synthase activity, the decreased superoxide dismutase activity and the increased lipid peroxidation induced by quinolinic acid (240 nmol/microl) 120 min after the toxin infusion. Enhanced caspase-3-like activity and DNA fragmentation were also reduced by the porphyrinate 24 h after the injection of the excitotoxin. Circling behavior from quinolinic acid-treated rats was abolished by Fe(TPPS) six days after quinolinic acid injection, while the striatal levels of GABA, measured one day later, were partially recovered. The protective effects that Fe(TPPS) exerted on quinolinic acid-induced lipid peroxidation and mitochondrial dysfunction in synaptic vesicles suggest a primary action of the porphyrinate as an antioxidant molecule. In vivo findings suggest that the early production of peroxynitrite, altogether with the enhanced risk of superoxide anion (O2*-) and nitric oxide formation (its precursors) induced by quinolinic acid in the striatum, are attenuated by Fe(TPPS) through a recovery in the basal activities of nitric oxide synthase and superoxide dismutase. The porphyrinate-mediated reduction in DNA fragmentation simultaneous to the decrease in caspase-3-like activation from quinolinic acid-lesioned rats suggests a prevention in the risk of peroxynitrite-mediated apoptotic events during the course of excitotoxic damage in the striatum. In summary, the protective effects that Fe(TPPS) exhibited both under in vitro and in vivo conditions support an active role of peroxynitrite and its precursors in the pattern of brain damage elicited by excitotoxic events in the experimental model of Huntington's disease. The neuroprotective mechanisms of Fe(TPPS) are discussed.

Selective alterations of transcription factors in MPP+-induced neurotoxicity in PC12 cells.

MPP(+) (1-methyl-4-phenylpyridinium; the active metabolite of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine)) depletes dopamine (DA) content and elicits cell death in PC12 cells. However, the mechanism of MPP(+)-induced neurotoxicity is still unclear. In this study, the dose response and time-course of MPP(+)-induced DA depletion and decreased cell viability were determined in nerve growth factor (NGF)-differentiated PC12 cells. The alteration of transcription factors (TFs) induced by MPP(+) from a selected dose level and time point was then evaluated using protein/DNA-binding arrays. K-means clustering analysis identified four patterns of protein/DNA-binding changes. Three of the 28 TFs identified in PC12 cells increased by 100% (p53, PRE, Smad SBE) and 2 decreased by 50% (HSE, RXR(DR1)) of control with MPP(+) treatment. In addition, three TFs decreased within the range of 33-50% (TFIID, E2F1, CREB) and two TFs increased within the range of 50-100% (PAX-5, Stat4). An electrophoretic mobility shift assay (EMSA) was used to confirm the changes of p53 and HSE. The observed changes in TFs correlated with the alterations of DA and cell viability. The data indicates that selective transcription factors are involved in MPP(+)-induced neurotoxicity and it provides mechanistic information that may be applicable to animal studies with MPTP and clinical studies of Parkinson's disease.

Inhibition of prolactin with bromocriptine for 28days increases blood-brain barrier permeability in the rat.

The blood-brain barrier (BBB) is necessary for the proper function of the brain. Its maintenance is regulated by endogenous factors. Recent evidences suggest prolactin (PRL) regulates the BBB properties in vitro, nevertheless no evidence of these effects have been reported in vivo. The aim of this study was to evaluate the role of PRL in the maintenance of the BBB in the rat. Male Wistar rats were treated with Bromocriptine (Bromo) to inhibit PRL production for 28days in the absence or presence of lipopolysaccharide (LPS). BBB permeability was evaluated through the Evans Blue dye and fluorescein-dextran extravasation as well as through edema formation. The expression of claudin-5, occludin, glial fibrillary acidic protein (GFAP) and the PRL receptor (PRLR) was evaluated through western blot. Bromo reduced the physiological levels of PRL at 28days. At the same time, Bromo increased BBB permeability and edema formation associated with a decrement in claudin-5 and occludin and potentiated the increase in BBB permeability induced by LPS. However, no neuroinflammation was detected, since the expression of GFAP was unchanged, as well as the expression of the PRLR. These data provide the first evidence that inhibition of PRL with Bromo affects the maintenance of the BBB through modulating the expression of tight junction proteins in vivo.

Histopathological and electrophysiological indices of rotenone-evoked dopaminergic toxicity: Neuroprotective effects of acetyl-L-carnitine.

Exposure to the natural pesticide, rotenone, a potent mitochondrial toxin, leads to degeneration in striatal nerve terminals and nigral neurons. Rotenone-induced behavioral, neurochemical and neuropathological changes in rats mimic those observed in Parkinson's disease (PD). Here, protective effects of acetyl-L-carnitine (ALC) in the brain dopaminergic toxicity after a prolonged exposure to rotenone were evaluated using electrophysiological and immunolabeling methods. Adult, male Sprague-Dawley rats were injected i.p. with rotenone alone (1 mg/kg) or rotenone with ALC (either 10 or 100 mg/kg; ALC10 or ALC100, respectively) once daily on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33 and 37. Control rats received either 100mg/kg ALC or vehicle (30% Solutol HS 15 in 0.9% saline) injections. Animals were weighed on injection days and monitored daily. Motor nerve conduction velocity (MCV) was assessed within two days after treatment using compound muscle action potentials (CMAP) detected from the tail muscle through surface receiver electrodes installed around the distal part of the tail. Rats were perfused immediately after testing with 4% paraformaldehyde and immunohistochemical analysis of dopamine transporter (DAT), tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and microglial CD11b marker was performed in the caudate-putamen (CPu) and the substantia nigra pars compacta (SNc) in order to estimate dopaminergic neuronal and transporter damage. Additionally, effects of ALC on preventing microglial or astrocytic hypertrophy were also evaluated. In rats exposed to rotenone and rotenone/ACL10, a significant increases in both proximal (S1) and distal (S2) motor latency and a decrease in MCV were detected in tail nerves (p<0.05). The conduction parameters in rats co-treated with rotenone/ACL100 were not different from control. It was found that 100 mg/kg ALC prevented loss of TH and a decline of DAT level in the midbrain and also prevented the activation of both microglia and astroglia after rotenone treatment. Data indicate neuroprotective effects of ALC in rotenone-evoked dopaminergic neurotoxicity.

Age-related susceptibility to 3,3'-iminodipropionitrile-induced olfactory mucosal damage.

3,3'-Iminodipropionitrile (IDPN) causes degeneration of the olfactory mucosa (OM) in rodents following systemic exposure. Approximately 30% of the OM degenerates in 21-day- and 10-week-old rats following a single 200 or 400 mg/kg intraperitoneal (i.p.) dose of IDPN, whereas 100% olfactory mucosal degeneration occurred in 21-month-old rats. Age-related changes in the flavin-containing monooxygenases (FMOs) or heat shock protein 70 (HSP70) were hypothesized to be responsible for altered olfactory mucosal susceptibility to IDPN. FMO activity in OM was higher than in liver in rats up to 40 weeks of age. Western blots of OM and liver revealed no change in FMO1 protein; however, FMO2, 3, and 5 decreased in olfactory microsomes with age. FMO3 and FMO5 increased in liver microsomes with age. Heat shock protein 70 did not differ between 10-week- and 10-month-old rats in either tissue. The mechanism underlying the increased susceptibility of older rats is likely a complex interaction between the activities of one or more of the enzymes involved in IDPN metabolism in OM and liver.