Coulomb explosion imaging of CH3I and CH2ClI photodissociation dynamics.

The photodissociation dynamics of CH3I and CH2ClI at 272 nm were investigated by time-resolved Coulomb explosion imaging, with an intense non-resonant 815 nm probe pulse. Fragment ion momenta over a wide m/z range were recorded simultaneously by coupling a velocity map imaging spectrometer with a pixel imaging mass spectrometry camera. For both molecules, delay-dependent pump-probe features were assigned to ultraviolet-induced carbon-iodine bond cleavage followed by Coulomb explosion. Multi-mass imaging also allowed the sequential cleavage of both carbon-halogen bonds in CH2ClI to be investigated. Furthermore, delay-dependent relative fragment momenta of a pair of ions were directly determined using recoil-frame covariance analysis. These results are complementary to conventional velocity map imaging experiments and demonstrate the application of time-resolved Coulomb explosion imaging to photoinduced real-time molecular motion.

Traditional Tibetan Medicine Induced High Methylmercury Exposure Level and Environmental Mercury Burden in Tibet, China.

Highly elevated concentrations of total mercury (THg) and methylmercury (MeHg) were found in the municipal sewage in Tibet. Material flow analysis supports the hypothesis that these elevated concentrations are related to regular ingestion of Hg-containing Traditional Tibetan Medicine (TTM). In Tibet in 2015, a total of 3600 kg of THg was released from human body into the terrestrial environment as a result of TTM ingestion, amounting to 45% of the total THg release into the terrestrial environment in Tibet, hence substantially enhancing the environmental Hg burden. Regular ingestion of TTM leads to chronic exposure of Tibetans to inorganic Hg (IHg) and MeHg, which is 34 to 3000-fold and 0-12-fold higher than from any other known dietary sources, respectively. Application of a human physiology model demonstrated that ingestion of TTM can induce high blood IHg and MeHg levels in the human body. Moreover, 180 days would be required for the MeHg to be cleared out of the human body and return to the initial concentration i.e. prior to the ingestion of 1 TTM pill. Our analysis suggests that high Hg level contained in TTM could be harmful to human health and elevate the environmental Hg burden in Tibet.

The expanding role of primary care in cancer control.

The nature of cancer control is changing, with an increasing emphasis, fuelled by public and political demand, on prevention, early diagnosis, and patient experience during and after treatment. At the same time, primary care is increasingly promoted, by governments and health funders worldwide, as the preferred setting for most health care for reasons of increasing need, to stabilise health-care costs, and to accommodate patient preference for care close to home. It is timely, then, to consider how this expanding role for primary care can work for cancer control, which has long been dominated by highly technical interventions centred on treatment, and in which the contribution of primary care has been largely perceived as marginal. In this Commission, expert opinion from primary care and public health professionals with academic and clinical cancer expertise­from epidemiologists, psychologists, policy makers, and cancer specialists­has contributed to a detailed consideration of the evidence for cancer control provided in primary care and community care settings. Ranging from primary prevention to end-of-life care, the scope for new models of care is explored, and the actions needed to effect change are outlined. The strengths of primary care­its continuous, coordinated, and comprehensive care for individuals and families­are particularly evident in prevention and diagnosis, in shared follow-up and survivorship care, and in end-of-life care. A strong theme of integration of care runs throughout, and its elements (clinical, vertical, and functional) and the tools needed for integrated working are described in detail. All of this change, as it evolves, will need to be underpinned by new research and by continuing and shared multiprofessional development.

Long-term outcome and quality of life after supercharged jejunal interposition for oesophageal replacement.

BACKGROUND: The consequences of major conduit necrosis following oesophagectomy are devastating. Jejunal interposition with vascular supercharging is an alternative reconstructive method if colon is unavailable. Aims of this study were to review the long-term outcome and quality of life of patients undergoing this surgery in our tertiary unit. METHODS: Patients undergoing oesophageal reconstruction with supercharged jejunum were identified and retrospective review of hospital notes performed. Each patient was then interviewed for follow up data and quality of life assessment using the EORTC QLQ-C30 questionnaire. RESULTS: Six patients (5 men) (median age 59 years (range 34-72) underwent supercharged pedicled jejunal (SPJ) interposition from May 2005-August 2010. Indications for surgery were loss of both gastric and colonic conduits following surgery for oesophageal cancer (n = 4), loss of gastric conduit and previous colectomy (n = 1) and lastly, gastric and colonic infarction in a strangulated paraoesophageal hernia (n = 1). Median time to reconstruction was 12 months [6-15 range]. There were no in-hospital deaths. Median postoperative stay was 46 days [13-118]. Three patients required surgical re-intervention for leak, sepsis and reflux, respectively. Median follow up was 6.5 years [range 7-102 months]. One patient died seven months following surgery due to respiratory complications. On follow up, 5 patients have an enteral diet without supplemental nutrition, maintaining weight and good quality of life scores. CONCLUSIONS: Supercharged jejunal interposition is a suitable alternative conduit for delayed oesophageal replacement in patients with otherwise limited reconstructive options. Good functional outcomes can be achieved despite formidable technical challenges in this group.

Towards bloodless cystectomy: a 10-year experience of intra-operative cell salvage during radical cystectomy.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Guidance from the UK National Institute for Health and Clinical Excellence (NICE) on the use of intraoperative cell savage (ICS) has been in place for over 3 years and recommends its routine usage in all patients undergoing radical pelvic urological surgery. The current series describes the contribution of ICS to contemporary blood conservation strategies and the goal of 'bloodless' cystectomy. OBJECTIVE: • To describe a 10-year experience of intra-operative cell salvage (ICS) during radical cystectomy at a regional cancer centre. PATIENTS AND METHODS: • Between 1(st) January 2001 and 31(st) December 2010, 213 consecutive patients underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer, with an ICS suction device used in theatre. • Surgery was performed by one of three consultant surgeons using an open technique with lymph node clearance to the iliac bifurcation. Orthotopic bladder substitution was performed in 25% of patients overall. • ICS data were collected prospectively on an electronic database and the institutional database was then cross-referenced with a complete review of patients' medical records, laboratory results and radiological investigations retrospectively. • Data collected included patient demographics, haemoglobin levels before and after surgery, the volume of ICS blood collected and re-infused, complications related to ICS usage, the volume of allogeneic red blood cells (RBCs) transfused, length of stay and overall patient survival at 3 and 5 years after surgery. RESULTS: • In all 213 cases described, ICS was used without complication, with no recorded episodes of device failure and no complications related to the use of cell salvage. • Overall, 91% of patients received ICS blood and 28% of patients avoided any further transfusion products. • The median (range) follow-up for the cohort was 24 (9-119) months. • Seventy percent of the transfusion requirement for patients who underwent surgery in 2001 was met using allogeneic RBC transfusion but by 2010, as blood loss markedly reduced, ICS blood was able to provide ∼70% of overall transfusion requirements. As a consequence, the percentage of patients avoiding an allogeneic RBC transfusion significantly increased during the 10-year period, such that 70% of patients avoided allogeneic RBC transfusion in 2010 compared with only 10-20% in the period 2001-2003 • The overall survival rate at 3 and 5 years was 58% and 49%, respectively. CONCLUSIONS: • In conclusion, the use of ICS during radical cystectomy is safe; it is capable of meeting the majority of or, in some cases, the total blood product requirement for individual patients. As a result, it decreases the need for allogeneic RBC transfusion and hence the associated risks. Current follow-up shows no apparent risk of decreased long-term survival from an oncological perspective. • The authors advocate routine availability of ICS for all major urological oncology cases.

Myths that persist about orofacial myology.

This article addresses many myths that have persisted over the years in dentistry and orofacial myology regarding the nature of orofacial myofunctional disorders (OMD's). Myths include 1) the concept that the term "tongue thrusting" includes the rest posture; 2) that there is an excessive amount of pressure exerted against the anterior teeth in swallows, that swallowing pressures add up, and the frequency of swallowing has an impact on the dentition; 3) the idea that the tongue is the strongest muscle in the body; 4) the view that a muscle will be the winner in any tug of war between muscle and bone; 5) the claim that a tongue thrust can cause an open bite malocclusion; 6) the claim that a tongue thrust can cause a Class II malocclusion; 7) the claim that the tongue molds the palatal vault; 8) the notion that a low tongue tip posture at rest presents a problem; and 9) the claim that OMD's represent a muscle imbalance that can be brought into balance with therapy. Each of these false claims or "myths" is discussed and corrected, with the positive acknowledgement that clinicians are abandoning the incorrect notion of muscle balance and imbalance as had been claimed previously.

Auditory gating in rat hippocampus and medial prefrontal cortex: effect of the cannabinoid agonist WIN55,212-2.

Sensory gating can be assessed in rodents and humans using an auditory conditioning (C)-test (T) paradigm, with schizophrenic patients exhibiting a loss of gating. Dysregulation of the endocannabinoid system has been proposed to be involved in the pathogenesis of schizophrenia. We studied auditory gating and the effects of the cannabinoid agonist WIN55,212-22 on gating in CA3 and dentate gyrus (DG) of the hippocampus and medial prefrontal cortex (mPFC) in male Lister hooded rats using in vivo electrophysiology. The effects of a single dose of WIN55,212-2 on the N2 local field potential (LFP) test/conditioning amplitude ratios (T/C ratio) and response latencies were examined. In rats that demonstrated gating of N2, mPFC showed higher T/C ratios and shorter conditioning response latencies compared to DG and CA3. WIN55,212-2 disrupted auditory gating in all three areas with a significant increase in test amplitudes in the gating rats. A group of non-gating rats demonstrated higher test amplitudes and higher T/C ratios compared to gating rats. WIN55,212-2 had no effect on T/C ratios in the non-gating rats. The cannabinoid receptor (CB1) antagonist SR141716A prevented WIN55,212-2 induced disruption of gating. This study demonstrates gated auditory-evoked responses in CA3, DG and mPFC. The mPFC showed an early phase of gating which may later be modulated by CA3 and DG activity. Furthermore, cannabinoid receptor activation disrupted auditory gating in CA3, DG and mPFC, an effect which was prevented by CB1 receptor antagonism. The results further demonstrate the presence of a non-gating rat population which responded differently to cannabinoid agonists.

Lung epithelial cells release ATP during ozone exposure: signaling for cell survival.

The common air pollutant ozone causes acute toxicity to human airways. In primary and transformed epithelial cells from all levels of human or rat airways, ozone levels relevant to air pollution (50-200 ppb) increased extracellular [ATP] within 7-30 min. A human bronchial epithelial cell line (16HBE14o(-)) that forms electrically resistant polarized monolayers had up to 10-fold greater apical than basolateral surface extracellular [ATP] within 7 min of ozone exposure. Increased extracellular [ATP] appeared due to ATP secretion or release because (1) inhibition of ectonucleotidase (cell surface enzyme(s) which degrade ATP) by ozone did not occur until >120 min of ozone exposure and (2) brefeldin A, a secretory inhibitor, eliminated elevation of extracellular [ATP] without affecting intracellular ATP. Extracellular ATP protected against ozone toxicity in a P2Y receptor-dependent manner as (1) removal of ATP and adenosine by apyrase and adenosine deaminase, respectively, potentiated ozone toxicity, (2) extracellular supplementation with ATP, a poorly hydrolyzable ATP analog ATPgammaS, or UTP inhibited apoptotic and necrotic ozone-mediated cell death, and (3) ATP-mediated protection was eliminated by P2 and P2Y receptor inhibitors suramin and Cibacron blue (reactive blue 2), respectively. The decline in glucose uptake caused by prolonged ozone exposure was prevented by supplemental extracellular ATP, an effect blocked by suramin. Further, Akt and ERK phosphorylation resulted from exposure to supplemental extracellular ATP. Thus, extracellularly released ATP signals to prevent ozone-induced death and supplementation with ATP or its analogs can augment protection, at least in part via Akt and /or ERK signaling pathways and their metabolic effects.

A serotonin receptor antagonist, but not melatonin, modulates hormonal responses to capture stress in two populations of garter snakes (Thamnophis sirtalis parietalis and Thamnophis sirtalis concinnus).

Hormonal and behavioral responses to a stressor depend on many factors, including the influence of other hormones. We examined the role of melatonin in modulating hormonal responses to capture stress in two populations of male garter snakes, Thamnophis sirtalis. Studies of red-sided (T. sirtalis parietalis) and red-spotted (T. sirtalis concinnus) garter snakes were conducted in the field with free-living snakes. Populations of red-sided garter snakes in south-central Manitoba, Canada undergo a period of winter dormancy for approximately 8 months each year followed by an attenuated mating season (4-5 weeks) in early spring. In contrast, the mid-latitude red-spotted garter snake in western Oregon, USA has an extended breeding season and can be active during 10-12 months of the year given appropriate environmental conditions. We chose to study these two populations of garter snakes to investigate possible variation in melatonin function among snakes with different suites of environmental adaptations. To better address these questions, we also examined the effects of 5-hydroxytryptophan (a precursor of melatonin synthesis) and ketanserin (a serotonergic type 2A receptor antagonist) on hormonal responses to capture stress. We observed a trend of increased corticosterone and decreased androgen concentrations in northern-latitude red-sided garter snakes (T. sirtalis parietalis) subjected to 4 h of capture stress during the spring. However, these differences were not statistically significant. During the fall, red-sided garter snakes showed no change in corticosterone or androgen concentrations in response to the capture stress treatments. We speculate that northern-latitude red-sided garter snakes suppress hormonal responses to capture stress during preparation for winter dormancy. Treatment with melatonin, 5-hydroxytryptophan, or ketanserin did not significantly influence corticosterone or androgen concentrations of northern-latitude red-sided garter snakes during the spring or fall. Mid-latitude red-spotted garter snakes (T. sirtalis concinnus) from Oregon showed a statistically significant increase in corticosterone concentrations in response to 4 h of capture stress; treatment with melatonin, 5-hydroxytryptophan, or ketanserin prior to capture stress had no significant influence on plasma corticosterone concentrations. Androgen concentrations of mid-latitude red-spotted garter snakes in response to capture stress were significantly lower than those of non-stressed control snakes. Neither melatonin nor 5-hydroxytryptophan influenced the change in androgen concentrations during capture stress. However, androgen concentrations of snakes treated with ketanserin prior to 4 h of capture stress did not differ significantly from those of non-stressed control snakes. These studies suggest that melatonin does not modulate hormonal responses to capture stress in this ectothermic model. Our results also suggest that a serotonin-regulated system may play a role in modulating the activity of the hypothalamic-pituitary-gonadal axis during physiological stress responses.

A retrospective and prospective view of orofacial myology.

Orofacial myofunctional disorders include specific conditions or behaviors that can have a negative impact on oral postures and functions. Historically, interest has focused on behaviors in the horizontal plane, highlighted by tongue thrusting. Currently, the scope of practice also includes tongue forward posturing, lip incompetence, open mouth rest posture, thumb and finger sucking, bruxism, and biting habits involving lips, fingers, tongue and cheeks. The common denominator for myofunctional conditions is a change in the inter-dental arch vertical rest posture dimension, the dental freeway space. The purposes of myofunctional therapy include normalizing the freeway space dimension by eliminating noxious habits or postures related to freeway space change. Improving cosmesis with a lips-together rest posture is also an important treatment goal. The clinical significance of the freeway space is explained in terms of the dental consequences of differential eruption patterns that can develop from postural modification of the freeway space. When the freeway space is opened for extended periods beyond the normal range, the tongue can act as a functional appliance and contribute to the development of anterior open bite or a Class II malocclusion. A clinical procedure is proposed for evaluating the freeway space dimension and incorporating the information into treatment planning and evaluation of treatment success. While dentistry/orthodontics has a primary focus on dental occlusion, or teeth-together relationships, orofacial myologists focus on teeth-apart behaviors and postures that can lead to, or have already resulted in malocclusion.

Methylmercury accumulation and fluxes across the intestine of channel catfish, Ictalurus punctatus.

The excised intestines of channel catfish, Ictalurus punctatus, were perfused at 20 or 4 degrees C for 1 h 45 min, with methylmercury (CH(3)HgCl) alone, or in the presence of excess L-cysteine (L-Cys), D-cysteine (D-Cys), L-methionine (L-Met); or with ouabain or probenecid to identify the potential CH(3)Hg(II) uptake pathways in fish intestines. A temperature effect was noted, with CH(3)Hg(II) concentrations in tissues perfused at 20 degrees C being higher than at 4 degrees C, substantiating the idea that mechanisms requiring metabolic energy are involved in CH(3)Hg(II) uptake in fish intestines. The results indicate that, when CH(3)Hg(II) is complexed as the CH(3)Hg-L-Cys complex, it is taken up via an L-neutral amino acid carrier and rapidly transported to the serosal side of the intestine. Methylmercury uptake could be inhibited by probenecid and ouabain, although probenecid had less impact on CH(3)Hg(II) uptake than ouabain. Our results for CH(3)Hg(II) uptake in the presence of D-Cys, L-Met in excess of L-Cys, or with a metal mixture further established that CH(3)Hg(II) uptake across fish intestines occurs via a variety of pathways, including an energy-dependent L-neutral amino acid carrier, and that the route and amount of accumulation were a function of CH(3)Hg(II) speciation in the digestive tract of the fish.

Effect of ligands and other metals on the uptake of mercury and methylmercury across the gills and the intestine of the blue crab (Callinectes sapidus).

Using the perfusion method, we compared the accumulation and flux of inorganic mercury (Hg) and methylmercury (CH(3)Hg) across the gills and intestine of the blue crab, Callinectes sapidus. The accumulation and transfer processes were studied for each form by exposing the organs in the presence of specific ligands and other metals. While binding of Hg and CH(3)Hg to organic ligands reduced the rate of uptake in most instances, the differences in accumulation could not be explained only in terms of passive diffusive uptake. Thus, it appears that Hg and CH(3)Hg accumulation is dominated by ligand exchange or facilitated transport processes. Exposure of the gills and intestine in the presence of a suite of metals and metalloids showed that inorganic Hg and CH(3)Hg uptake was largely by different mechanisms to that of the other elements, as there was little interaction in terms of uptake rate. Overall, the results of this study suggest that inorganic Hg and CH(3)Hg uptake into the gills and intestine of this invertebrate is by a variety of pathways, both active and passive.