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The objective of this study was to report outcomes of early cleft palate repair in infants born with Robin sequence (RS). A retrospective case series in a tertiary referral paediatric hospital was carried out, examining a consecutive series of 69 infants born with RS and cleft palate. A minimally invasive approach was taken to upper airway obstruction, with liberal nasopharyngeal airway (NPA) and non-invasive ventilation (NIV) use, guided by sleep studies. The palate was repaired between 6 and 9 months with a modified Malek technique. The most frequently used airway adjunct (59.4% of patients) was an NPA and the median duration of use was 5.6 months. All patients underwent a modified Malek cleft palate repair at a median of 7 months of age. Overnight oximetry demonstrated higher mean oxygen saturation (SpO 2) across the group from initial neonatal admission to discharge (median 96.5% (interquartile range [IQR] 95–98%) vs 97.45% (IQR 96.5–98%) (P = 0.2, N = 34). Of those with a cardiorespiratory polysomnogram, the obstructive apnoea-hypopnea index (OAHI) was significantly lower postoperatively (5.9 vs 2.8, P = 0.028). This study supports the use of non-surgical airway strategies and early cleft palate repair in infants born with RS and cleft palate. [ABSTRACT FROM AUTHOR]

Homologous recombination was used to target a null mutation in the granzyme B gene in the H-2b mice. While these mice are normal in lymphopoiesis, peripheral lymphoid tissue formation, T cell response to mitogenic and allogenic stimuli and the cytotoxic T lymphocytes do not promote DNA fragmentation and apoptosis in allogenic target cells.

A cyclic alkyne polymerization catalyst undergoes, with heat or a Lewis base, a rearrangement to form a vanadium imido monoazabutadieneallenyl complex, which is no longer an active catalyst. [Display omitted] We show in this study how the catalyst for the cyclic polymerization of phenylacetylene, a high-spin vanadium(III) complex supported by the β-diketiminate (BDI) scaffold, [(BDI)V(κ2-C,C-Me 3 SiC 3 SiMe 3)] (1) (BDI = [ArNC(CH 3)] 2 , Ar = 2,6- i Pr 2 C 6 H 3), can convert thermally or with a Lewis base to a low-spin [VIII] complex [{ArNC(CH 3)CHC(CH 3)C(SiMe 3)CC(SiMe 3)}V=NAr] (2). Complex 2 was characterized spectroscopically by multinuclear NMR (1H, 13C, 29Si, 51V), IR, and UV–Vis in addition to single crystal X-ray diffraction analysis. Complex 2 was found to be inactive towards the polymerization of phenylacetylene, unlike its predecessor 1 , therefore suggesting that such rearrangement might be the modus operandi for catalyst deactivation. We propose the 1 → 2 transformation to involve a denticity change from κ2-C,C-Me 3 SiC 3 SiMe 3 to a κ1-alkylidene-alkylnyl, followed by an intra-molecular cross-metathesis pathway involving the V=C bond of the alkylidene-alkynyl ligand with the imine group of the BDI ligand to eventually form the vanadium imido ligand and monoazabutadieneallenyl (MADA−) moiety. [ABSTRACT FROM AUTHOR]

Crude methanol extract of the leaves of Caesalpinia welwitschiana was found to possess moderate larvicidal activity against second-instar larvae of Tuta absoluta Meyrick. Bioassay-guided fractionation of this extract led to the isolation of two oxygenated cyclohexene derivatives, welwitschianalol A ( 1, (1 α, 2 β )-2-acetoxy-1-hydroxy-1- benzoyloxymethylcyclohex-5-ene) and B ( 2, (1 α, 2 β )-2- benzoyloxy −1-cinnamoyloxymethyl-1-hydroxycyclohex-5-ene), together with eight known compounds, comprising bonducellin, dipteryxic acid, 3′-hydroxygenkwarin, afzelin, quercitrin, myricitrin, methyl gallate and gallic acid. The structures of the unknown compounds as well as those of the known ones were elucidated based on their MS, 1D and 2D NMR spectra, and in the case of known compounds, by comparison with the reported data. Each of welwitschianalol A and B, bonducellin, dipteryxic acid, afzelin, quercitrin and myricitrin showed more than 50% mortality of T. absoluta larvae at 5 ppm, which was comparable to that of azadirachtin (the most bioactive constituent of Azadirachta indica ). The most potent constituent of C. welwitschiana was welwitschianalol B with LD 50 of 3.8 ppm, which was higher than that of azadirachtin (LD 50 of 7.8 ppm). [ABSTRACT FROM AUTHOR]

We present the case of a fifteen-year-old male with hypertrophic pyloric stenosis (HPS) thought to have originated in early infancy when chronic non-bilious emesis, early satiety and failure to thrive were evident. He developed two episodes of perforated pre-pyloric ulcer at ages 12- and 14-years. Work up for chronic Helicobacter pylori and Zollinger Ellison syndrome were negative. An upper GI study revealed a massively enlarged stomach and delayed gastric emptying. Endoscopic ultrasound revealed a thickened pylorus and a narrow pyloric canal. Electrogastrogram and antroduodenal motility studies supported a mechanical gastric outlet obstruction. A distal gastrectomy with Billroth I reconstruction was performed. One year after surgery, the patient's symptoms resolved and he had gained 14.5 kg in weight. This is a very rare case of HPS presenting after infancy and emphasizes the importance of early diagnosis of HPS to prevent long term complications including failure to thrive and death. [ABSTRACT FROM AUTHOR]

Objective Tongue strength, timing, and coordination deficits may underlie age-related swallowing function. Retrusive tongue actions are likely important in retrograde bolus transport. However, age-related changes in retrusive tongue muscle contractile properties have not been identified in animal studies. Because previous studies employed whole hypoglossal nerve stimulation that activated both protrusive and retrusive tongue muscles, co-contraction may have masked retrusive muscle force decrements. The hypotheses of this study were: (1) retrusive tongue muscle contraction forces would be diminished and temporal characteristics prolonged in old rats when lateral nerves were selectively activated, and (2) greater muscle contractile forces with selective lateral branch stimulation would be found relative to whole hypoglossal nerve stimulation. Design Nineteen Fischer 344/Brown Norway rats (9 old, 10 young adult) underwent tongue muscle contractile property recording elicited by: (1) bilateral whole hypoglossal nerve stimulation, and (2) selective lateral branch stimulation. Twitch contraction time (CT), half-decay time, maximal twitch and tetanic forces, and a fatigue index were measured. Results For whole nerve stimulation, CT was significantly longer in the old group. No significant age group differences were found with selective lateral nerve stimulation. Significantly reduced twitch forces (old group only), increased tetanic forces and significantly less fatigue were found with selective lateral nerve stimulation than with whole hypoglossal stimulation. Conclusions Retrusive tongue forces are not impaired in old rats. Deficits observed in swallowing with aging may be due to other factors such as inadequate bolus propulsive forces, mediated by protrusive tongue muscles, or timing/coordination of muscle actions. [ABSTRACT FROM AUTHOR]

Background As a major zoonotic pathogen, characterization of the infectivity and pathogenicity of Coxiella burnetii is essential to understand Q-fever epidemiology. Objectives We want to extend a recently published human dose response model based on experimental challenge of young adult males to include other age groups and both genders. Additionally, we can estimate the spatial distribution of exposure based on observed outbreak data. Methods Dose response assessment based on human challenge, is extended by including outbreak data, using location of cases as a proxy for exposure. This allows estimation of the influence of age and gender on the probability of developing symptoms of acute respiratory illness. Results In an outbreak in Switzerland, in 1983, exposure to C. burnetii was shown to depend strongly on distance from the source. The susceptibility of males to develop Q-fever decreases with age, while in females, middle-aged women appear to have the lowest risk. Conclusions The published dose response model for Q-fever, based on experimental challenge of a small group of human volunteers, has been updated with data from a well studied outbreak. Infectivity estimates remain high, and even low doses (of 10 or fewer organisms) cause a high risk of illness. [ABSTRACT FROM AUTHOR]

Highlights: [•] Role for central allopregnanolone in reduced neuroendocrine stress responses. [•] Allopregnanolone and oxytocin system interactions for minimising preterm birth risk. [•] Disrupted neurosteroidogenesis in compromised pregnancy and offspring outcomes. [•] Role for progesterone or allopregnanolone in correcting adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Lesions at the thoracic inlet are difficult to access via a thoracic or cervical approach. The use of the anterior cervico-thoracic trapdoor incision has been reported to give good exposure to the anterior superior mediastinum in adults. We report our experience of four cases where a trapdoor incision was used to gain excellent access and exposure to thoracic inlet pathology in children. [Copyright &y& Elsevier]

Abstract: Deficits in tongue function in conjunction with airway compromise can contribute to dysphagia associated with Parkinson disease (PD). However, it is unknown if these deficits are related to the primary disease pathology in PD, nigrostriatal dopamine depletion. To directly study the impact of striatal dopamine depletion on tongue function, we used unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle and measured tongue force and timing parameters during a complex tongue protrusion task for a water reward. Maximal and average forces were significantly diminished and average press time was significantly longer after neurotoxin administration, reflecting aspects of bradykinesia and hypokinesia associated with PD. Our findings suggest that even unilateral deficits to the nigrostriatal dopamine system may be contributing to some of the lingual sensorimotor deficits seen in PD. Because previous research in rat models of PD has shown that targeted training of the limb can rescue behavioral deficits and spare striatal dopamine neurons, early intervention for cranial sensorimotor deficits may also be indicated. [Copyright &y& Elsevier]

Abstract: Supraoptic nucleus (SON) neurons secrete either oxytocin or vasopressin into the bloodstream from their axon terminals in the posterior pituitary gland. SON neurons are powerfully inhibited by the classical μ-opioid receptor agonist, morphine. Oxytocin neurons develop morphine dependence when chronically exposed to this opiate, and undergo robust withdrawal excitation when morphine is subsequently acutely antagonized by naloxone. Morphine withdrawal excitation is evident as an increased firing rate and is associated with an increased post-spike excitability that is consistent with the expression of an enhanced post-spike afterdepolarization (ADP) during withdrawal. Here, we used sharp electrode recording from SON neurons in hypothalamic explants from morphine naïve and morphine treated rats to determine the effects of morphine on the ADP, and to test the hypothesis that morphine withdrawal increases ADP amplitude in SON neurons. Acute morphine administration (0.05–5.0 μM) caused a dose-dependent hyperpolarization of SON neurons that was reversed by concomitant administration of 10 μM naloxone, or by washout of morphine; counter-intuitively, acute exposure to 5 μM morphine increased ADP amplitude by 78 ± 11% (mean ± SEM). Naloxone-precipitated morphine withdrawal did not alter baseline membrane potential in SON neurons from morphine treated rats, but increased ADP amplitude by 48 ± 11%; this represents a hyper-activation of ADPs because the basal amplitude of the ADP was similar in SON neurons recorded from explants prepared from morphine naïve and morphine treated rats. Hence, an enhanced ADP might contribute to morphine withdrawal excitation of oxytocin neurons. [Copyright &y& Elsevier]

Abstract: The major changes in highly dynamic neuroendocrine systems that are essential for establishing and maintaining pregnancy are outlined from studies on rodents. These changes optimise the internal environment to provide the life support system for the placenta, embryo and fetus. These include automatic prevention of further pregnancy, blood volume expansion, increased appetite and energy storage. The brain regulates these changes, in response to steroid (estrogens, progesterone) and peptide (lactogens, relaxin) hormone signals. Activation of inhibitory endogenous opioid mechanisms in the brain in late pregnancy restrains premature secretion of oxytocin, and attenuates hypothalamo-pituitary-adrenal (HPA) responses to stress. This opioid mechanism is activated by allopregnanolone, a neuroactive progesterone metabolite. The significance of reduced HPA axis responses in shifting maternal metabolic balance, and in protecting the fetuses from adverse programming of HPA axis stress responsiveness and anxious behaviour in later life is critically discussed. Experimental studies showing sex-dependent fetal programming by maternal stress or glucocorticoid exposure in late pregnancy are reviewed. The possibility of over-writing programming in offspring through neurosteroid administration is discussed. The impact of maternal stress on placental function is considered in the context of reconciling studies that show offspring programming by stress in very early or late pregnancy produce similar phenotypes in the offspring. [Copyright &y& Elsevier]

Abstract: The female sex steroid hormones, estrogens and progesterone, are produced in large amounts in pregnancy, increasing as pregnancy progresses. These hormones have essential peripheral actions to maintain pregnancy, and to secure safe delivery at term. They also have important actions on the brain in pregnancy, generally through interactions with neuropeptide systems in the brain, or through modulating the actions of circulating peptide hormones on the brain. Together, these steroid–peptide links form short chains that evoke changes in central physiological systems that favour the pregnancy, including altered control of water and electrolyte balance, appetite and energy partitioning and stress responses. In parallel such links prepare the brain, through inhibition of oxytocin secretion until it is needed to support parturition and for immediate expression of maternal behaviour postpartum. We focus here on recent advances in understanding some of these steroid–peptide links, especially on non-classical progesterone actions through allopregnanolone, its neuroactive steroid metabolite, and opioid peptide mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Sensorimotor deficits affecting voice and swallowing ability can have a devastating impact on the quality of life of people with Parkinson disease (PD). Recent scientific findings in animal models of PD pinpoint targeted exercise therapy as a potential treatment to reduce neurochemical loss and decrease parkinsonian symptoms. Although there may be beneficial effects, targeted exercise therapy is not a standard component of therapy for the cranial sensiromotor deficits seen in PD. In this paper, we review the scientific evidence for targeted training for voice and swallowing deficits. The literature search revealed 19 publications that included targeted training for voice and only one publication that included targeted training for swallowing. We summarize 3 main findings: (1) targeted training may be associated with lasting changes in voice behavior; (2) targeted training of sensorimotor actions with anatomical or functional overlap with voice and swallowing may improve voice and swallowing to some degree, but it is unknown whether these effects endure over time; and (3) evidence regarding cranial sensorimotor interventions for Parkinson disease is sparse. We concluded that targeted training for voice and swallow is a promising but understudied intervention for cranial sensorimotor deficits associated with PD and posit that animal models can be useful in designing empirically based studies that further the science on targeted training. [Copyright &y& Elsevier]

Abstract: This paper explores the effect of cluster plasticisation on the autonomous damage initiated self healing behaviour of a partially neutralised poly(ethylene-co-methacrylic acid) ionomer copolymer, Surlyn 8940® (DuPont). Aliphatic di- and tri-carboxylic acid based modifiers and their analogues were blended with the ionomer at 10 wt% concentration using twin screw extrusion methods to study their effect upon self healing. In-situ mechanical evaluation of the healing process showed that carboxylic acid modifiers reduced the elastic properties of the blend, increased elastomeric behaviour and enhanced elastic healing. The sodium neutralised carboxylic acids analogues and succinamide modifiers displayed the opposite behaviour, increasing elastic properties, decreasing elastomeric behaviour and reducing elastic healing. A proposed relationship which accounted for both the elastic and elastomeric behaviour during impact was found to correlate well with independent measurements of elastic healing or hole closure. Thermal analysis suggested that the carboxylic acid modifiers plasticised the ionic clusters, reducing their strength and increasing their rate of recovery. The sodium neutralised analogues and succinamide modifiers, again conversely, produced negligible plasticisation but reduced the rate of reformation of the ionic clusters after annealing. Examination of the impact zone using scanning electron microscopy complemented the mechanical and thermal results revealing increased elastomeric and viscous behaviour for the carboxylic acid modified samples but increased brittle failure for the sodium neutralised analogues and succinamide modifiers. Systematic modification of the ionomer therefore has clearly illustrated the importance of the ionic clusters in determining static and dynamic properties. In addition to this, controlling their strength and mobility is shown to have a profound effect upon the efficiency of the damage initiated healing event. [Copyright &y& Elsevier]

In fibrotic conditions increases in TG2 activity has been linked to an increase in the deposition of extracellular matrix proteins. Using TG2 transfected Swiss 313 fibroblasts expressing TG2 under the control of the tetracycline-regulated inducible promoter, we demonstrate that induction of TG2 not only stimulates an increase in collagen and fibronectin deposition but also an increase in the expression of these proteins. Increased TG2 expression in these fibroblasts led to NF-κB activation, resulting in the increased expression of transforming growth factor (TGF) β1. In addition, cells overexpressing TG2 demonstrated an increase in biologically active TGFβ1 in the extracellular environment. A specific site-directed inhibitor of TG abolished the NF-κB and TGFβ1 activation and the subsequent elevation in the synthesis and deposition of extracellular matrix proteins, confirming that this process depends on the induction of transglutaminase activity. Treatment of TG2-induced fibroblasts with nontoxic doses of nitric oxide donor S-nitroso-N-acetylpenicillamine resulted in decreased TG2 activity and apprehension of the inactive enzyme on the cell surface. This was paralleled by a reduction in activation of NE-KB and TGFβ1 production with a subsequent decrease in collagen expression and deposition. These findings support a role for NO in the regulation of TG2 function in the extracellular environment. [ABSTRACT FROM AUTHOR]

Abstract: An explanation is proposed for the nuclear reactions that occur in the electrolysis class of LENR processes. The proposed explanation postulates that a proton, or deuteron, dissolved in the hydrogen bearing metal cathode, absorbs its associated atomic electron to become a short lived state of the neutron with the resulting neutrino in a singular wave function centered on the neutron. The energy required to initiate this endothermic reaction is supplied either by the ion current during electrolysis type experiments, or by ion bombardment in plasma type experiments. It is the energy of this bombardment of the cathode with heavy ions that creates a coherent polyplasmon field within crystalline metallic grains that are present in the metal cathode of typical active electrolysis cells. The LENR process consists of a second order reaction mediated by a coherent plasmon field excited in the conduction electrons in a hydrogen bearing metal that is in the form of crystalline grains of the order of a few microns in dimension. The coherent plasmon field in each grain is called a polyplasmon. The metallic grains typically form during solidification of a metal, the impurities being forced to the grain surfaces. The resulting grain thus forms a resonant structure that can be filled with a number of coherent plasmons, i.e., a polyplasmon. Energy from the polyplasmon is coupled to the nucleus via electron capture by hydrogen. Because the neutrino has mass, its wave function has a second class of solutions. This description can take the form of a short lived pairing with the neutron that results from electron capture by the hydrogen nucleus. This short-lived compound particle is named the “dion” and in the case of deuterium results in a “dineutron”. Because the dion and dineutron are formed with essentially thermal kinetic energy, they can capture in nearby nuclei, either in hydrogen or in the host metal. Most of the resulting exothermic nuclear energy is absorbed in the plasmon field by a variety of mechanisms that increase the intensity of the plasmon field and hence the rate of electron capture – that then increases the rate of nuclear reactions. This stochastic chain-reaction process continues in the grain until it is terminated by the random occurrence of losses preventing the continuation of sustaining nuclear reactions before the plasmon field decays away, or until the rise in temperature of the metal grain alters the physical properties of the metallic grain sufficiently to disrupt the polyplasmon field. Multiple reported experiments confirm that most of the nuclear energy released is absorbed by the host metallic cathode and the electrolyte. Calculations from first principles are consistent with many of the reported quantitative and qualitative phenomena. [Copyright &y& Elsevier]

Abstract: The spruce terminal weevil Pissodes strobi (Peck) is a major pest in western spruces, attacking trees of all ages beyond the juvenile stage, killing the leader and causing tree distortion. This paper describes a computer simulation model of the joint population dynamics within this tree/pest system, over the lifetime of a plantation, and is combined with the Province of British Columbia''s Tree and Stand Simulator (TASS) to drive individual tree growth and stand establishment and development. The model differs from current models of this system, and of other similar systems, in two important ways: (1) it simulates the entire life of a stand, from planting until harvest, and (2) it is based on the underlying biological processes that govern behavior of individual weevils on and in each tree. Each model simulation begins by planting a stand using tree materials from seed or clonal hedge orchards, choosing trees either individually and independently or in groups represented as clones or families. Stand growth and mortality are advanced through a juvenile period, after which weevils appear in the stand. From this time until harvest, the model simulates daily changes in the weevil populations on each tree, tracking mortality, oviposition, and juvenile maturation and emergence, as well as weevil movement from tree to tree. Once a year, the code projects tree mortality and growth, taking into account within-stand competition and damage to leaders caused by weevil attacks. At harvest, the model computes an estimate of the merchantable timber produced by the stand. As illustrations of model output, we present (1) simulated average numbers of adult and juvenile weevils in stands generated using materials from seed orchards, both throughout a single season and also through the years from stand planting until harvest; and (2) the differential effect of weevil damage on two tree genotypes, one resistant and one susceptible, in a stand composed of adjacent clonal blocks. The results of model simulations are in agreement with some of the population dynamics statistics observed in plantations, suggesting that the model reflects biological realism and can be used as a research or management tool. [Copyright &y& Elsevier]

Abstract: Oxytocin synthesised by magnocellular neurons in the supraoptic and paraventricular nuclei plays an important role in mammalian parturition. Accordingly, in late pregnant rats, oxytocin neurons are restrained from premature activation and stimulated oxytocin secretion is inhibited, preserving the expanded neurohypophysial oxytocin stores for parturition. A wide range of stressors stimulate oxytocin secretion in the rat. Some physical stressors, in particular immune challenge with systemic interleukin-1β (IL-1β, a cytokine that mimics infection) signal to magnocellular oxytocin neurons via brainstem noradrenergic neurons. Afferents relaying information from the uterus and birth canal also converge onto brainstem noradrenergic neurons and are robustly activated at parturition. Thus, quiescence of these inputs may be important in minimising the risk of preterm labour. Focussing on an immune challenge model (since infection is a major cause of preterm labour in women), we have found that the responsiveness of oxytocin neurons to IL-1β is markedly suppressed in late pregnancy. Here we discuss the mechanisms involved, which include induction of central inhibitory opioid tone by the progesterone neurosteroid metabolite, allopregnanolone, and act to prevent activation of oxytocin neurons by inappropriate stimuli at the end of pregnancy. [Copyright &y& Elsevier]

In supersymmetric grand unified theories (GUTs) based on S1/(Z2×Z′2) orbifold constructions in 5 dimensions, Standard Model (SM) matter and Higgs fields can be realized in terms of 5d hypermultiplets. These hypermultiplets can naturally have large bulk masses, leading to a localization of the zero modes at one of the two branes or to an exponential suppression of the mass of the lowest-lying non-zero mode. We demonstrate that these dynamical features allow for the construction of an elegant 3-generation SU(5) model in 5 dimensions that explains all the hierarchies between fermion masses and CKM matrix elements in geometrical terms. Moreover, if U(1)χ (where SU(5)×U(1)χ⊂SO(10)) is gauged in the bulk, but broken by the orbifold action at the SM brane, the right-handed neutrino mass scale is naturally suppressed relative to MGUT. Together with our construction in the charged fermion sector this leads, via the usual see-saw mechanism, to a realistic light neutrino mass scale and large neutrino mixing angles. [Copyright &y& Elsevier]