Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Magnetic-field-induced charge-stripe order in the high temperature superconductor YBa2Cu3Oy

Electronic charges introduced in copper-oxide planes generate high-transition temperature superconductivity but, under special circumstances, they can also order into filaments called stripes. Whether an underlying tendency of charges to order is present in all cuprates and whether this has any relationship with superconductivity are, however, two highly controversial issues. In order to uncover underlying electronic orders, magnetic fields strong enough to destabilise superconductivity can be used. Such experiments, including quantum oscillations in YBa2Cu3Oy (a notoriously clean cuprate where charge order is not observed) have suggested that superconductivity competes with spin, rather than charge, order. Here, using nuclear magnetic resonance, we demonstrate that high magnetic fields actually induce charge order, without spin order, in the CuO2 planes of YBa2Cu3Oy. The observed static, unidirectional, modulation of the charge density breaks translational symmetry, thus explaining quantum oscillation results, and we argue that it is most likely the same 4a-periodic modulation as in stripe-ordered cuprates. The discovery that it develops only when superconductivity fades away and near the same 1/8th hole doping as in La2-xBaxCuO4 suggests that charge order, although visibly pinned by CuO chains in YBa2Cu3Oy, is an intrinsic propensity of the superconducting planes of high Tc cuprates.Comment: For a final version, see http://www.nature.com/nature/journal/v477/n7363/full/nature10345.htm

Tension of knotted surgical sutures shows tissue specific rapid loss in a rodent model

<p>Abstract</p> <p>Background</p> <p>Every surgical suture compresses the enclosed tissue with a tension that depends from the knotting force and the resistance of the tissue. The aim of this study was to identify the dynamic change of applied suture tension with regard to the tissue specific cutting reaction.</p> <p>Methods</p> <p>In rabbits we placed single polypropylene sutures (3/0) in skin, muscle, liver, stomach and small intestine. Six measurements for each single organ were determined by tension sensors for 60 minutes. We collected tissue specimens to analyse the connective tissue stability by measuring the collagen/protein content.</p> <p>Results</p> <p>We identified three phases in the process of suture loosening. The initial rapid loss of the first phase lasts only one minute. It can be regarded as cutting through damage of the tissue. The percentage of lost tension is closely related to the collagen content of the tissue (r = -0.424; p = 0.016). The second phase is characterized by a slower decrease of suture tension, reflecting a tissue specific plastic deformation. Phase 3 is characterized by a plateau representing the remaining structural stability of the tissue. The ratio of remaining tension to initial tension of phase 1 is closely related to the collagen content of the tissue (r = 0.392; p = 0.026).</p> <p>Conclusions</p> <p>Knotted non-elastic monofilament sutures rapidly loose tension. The initial phase of high tension may be narrowed by reduction of the surgeons' initial force of the sutures' elasticity to those of the tissue. Further studies have to confirm, whether reduced tissue compression and less local damage permits improved wound healing.</p

Outcome reporting across randomized trials and observational studies evaluating treatments for twin–twin transfusion syndrome: systematic review

Objective Twin–twin transfusion syndrome (TTTS) is associated with significant mortality and morbidity. Potential treatments for the condition require robust evaluation. The aim of this study was to evaluate outcome reporting across observational studies and randomized controlled trials assessing treatments for TTTS. Methods Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE were searched from inception to August 2016. Observational studies and randomized controlled trials reporting outcome following treatment for TTTS in monochorionic–diamniotic twin pregnancy and monochorionic–triamniotic or dichorionic–triamniotic triplet pregnancy were included. Outcome reporting was systematically extracted and categorized. Results Six randomized trials and 94 observational studies were included, reporting data from 20 071 maternal participants and 3199 children. Six different treatments were evaluated. Included studies reported 62 different outcomes, including six fetal, seven offspring mortality, 25 neonatal, six early childhood and 18 maternal/operative outcomes. Outcomes were reported inconsistently across trials. For example, when considering offspring mortality, 31 (31%) studies reported live birth, 31 (31%) reported intrauterine death, 49 (49%) reported neonatal mortality and 17 (17%) reported perinatal mortality. Four (4%) studies reported respiratory distress syndrome. Only 19 (19%) studies were designed for long‐term follow‐up and 11 (11%) of these reported cerebral palsy. Conclusions Studies evaluating treatments for TTTS have often neglected to report clinically important outcomes, especially neonatal morbidity outcomes, and most are not designed for long‐term follow‐up. The development of a core outcome set could help standardize outcome collection and reporting in TTTS studies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd

Non-Functional Parathyroid Carcinoma: A Review of the Literature and Report of a Case Requiring Extensive Surgery

Parathyroid carcinoma is a rare malignancy, and only accounts for 0.5–2% of cases of primary hyperparathyroidism. Less than 10% of parathyroid carcinomas are non-functional, and as such, they have been rarely reported in the literature. Importantly, margin status at resection is related to prognosis, and only a handful of case reports of non-functional carcinoma note this important parameter. Here we report the first case of non-functional parathyroid carcinoma with negative margins, and review the literature on this rare entity. Whether functional or non-functional, parathyroid carcinoma can often be difficult to differentiate from benign parathyroid adenoma. While diagnosis has been based on clinical and histological criteria, recent data concerning the molecular underpinnings of parathyroid carcinoma may allow for improved accuracy in distinguishing benign and malignant parathyroid tumors

Resource Selection and Its Implications for Wide-Ranging Mammals of the Brazilian Cerrado

Conserving animals beyond protected areas is critical because even the largest reserves may be too small to maintain viable populations for many wide-ranging species. Identification of landscape features that will promote persistence of a diverse array of species is a high priority, particularly, for protected areas that reside in regions of otherwise extensive habitat loss. This is the case for Emas National Park, a small but important protected area located in the Brazilian Cerrado, the world's most biologically diverse savanna. Emas Park is a large-mammal global conservation priority area but is too small to protect wide-ranging mammals for the long-term and conserving these populations will depend on the landscape surrounding the park. We employed novel, noninvasive methods to determine the relative importance of resources found within the park, as well as identify landscape features that promote persistence of wide-ranging mammals outside reserve borders. We used scat detection dogs to survey for five large mammals of conservation concern: giant armadillo (Priodontes maximus), giant anteater (Myrmecophaga tridactyla), maned wolf (Chrysocyon brachyurus), jaguar (Panthera onca), and puma (Puma concolor). We estimated resource selection probability functions for each species from 1,572 scat locations and 434 giant armadillo burrow locations. Results indicate that giant armadillos and jaguars are highly selective of natural habitats, which makes both species sensitive to landscape change from agricultural development. Due to the high amount of such development outside of the Emas Park boundary, the park provides rare resource conditions that are particularly important for these two species. We also reveal that both woodland and forest vegetation remnants enable use of the agricultural landscape as a whole for maned wolves, pumas, and giant anteaters. We identify those features and their landscape compositions that should be prioritized for conservation, arguing that a multi-faceted approach is required to protect these species

Overview of medical errors and adverse events

Safety is a global concept that encompasses efficiency, security of care, reactivity of caregivers, and satisfaction of patients and relatives. Patient safety has emerged as a major target for healthcare improvement. Quality assurance is a complex task, and patients in the intensive care unit (ICU) are more likely than other hospitalized patients to experience medical errors, due to the complexity of their conditions, need for urgent interventions, and considerable workload fluctuation. Medication errors are the most common medical errors and can induce adverse events. Two approaches are available for evaluating and improving quality-of-care: the room-for-improvement model, in which problems are identified, plans are made to resolve them, and the results of the plans are measured; and the monitoring model, in which quality indicators are defined as relevant to potential problems and then monitored periodically. Indicators that reflect structures, processes, or outcomes have been developed by medical societies. Surveillance of these indicators is organized at the hospital or national level. Using a combination of methods improves the results. Errors are caused by combinations of human factors and system factors, and information must be obtained on how people make errors in the ICU environment. Preventive strategies are more likely to be effective if they rely on a system-based approach, in which organizational flaws are remedied, rather than a human-based approach of encouraging people not to make errors. The development of a safety culture in the ICU is crucial to effective prevention and should occur before the evaluation of safety programs, which are more likely to be effective when they involve bundles of measures

Levelt’s laws do not predict perception when luminance- and contrast-modulated stimuli compete during binocular rivalry

Incompatible patterns viewed by each of the two eyes can provoke binocular rivalry, a competition of perception. Levelt’s first law predicts that a highly visible stimulus will predominate over a less visible stimulus during binocular rivalry. In a behavioural study, we made a counterintuitive observation: low visibility patterns can predominate over high visibility patterns. Our results show that none of Levelt’s binocular rivalry laws hold when luminance-modulated (LM) patterns compete with contrast-modulated (CM) patterns. We discuss visual saliency, asymmetric feedback, and a combination of both as potential mechanisms to explain the CM versus LM findings. Competing orthogonal LM stimuli do follow Levelt’s laws, whereas only the first two laws hold for competing CM stimuli. The current results provide strong psychophysical evidence for the existence of separate processing stages for LM and CM stimuli