Shared and selective neural correlates of inhibition, facilitation, and shifting processes during executive control

A network of prefrontal and parietal regions has been implicated in executive control processes. However, the extent to which individual regions within this network are engaged in component control processes, such as inhibition of task-irrelevant stimulus attributes or shifting (switching) between attentional foci, remains controversial. Participants (N = 17) underwent functional magnetic resonance imaging while performing a global–local task in which the global and local levels could facilitate or interfere with one another. Stimuli were presented in blocks in which participants either constantly shifted between the global and local levels, or consistently responded to one level only. Activations related to inhibition and shifting processes were observed in a large network of bilateral prefrontal, parietal, and basal ganglia regions. Region of interest analyses were used to classify each region within this network as being common to inhibition and shifting, or preferential to one component process. Several regions were classified as being preferential to inhibition, including regions within the dorsolateral and ventrolateral prefrontal cortex, the parietal lobes, and the temporal–parietal junction. A limited set of regions in the parietal lobes and left dorsolateral prefrontal cortex were classified as preferential to shifting. There was a very large set of regions displaying activation common to both inhibition and shifting processes, including regions within the dorsolateral prefrontal cortex, anterior cingulate, and basal ganglia. Several of these common regions were also involved during facilitation, suggesting that they are responsive to the number of task-salient channels of information, rather than purely to demands on control processes.National Institute of Mental Health (U.S.) (MH061426)National Institute on Aging (AG021847

Effects of daily porcine somatotropin administration on tile performance and carcass characteristics of finishing swine

One hundred forty-four pigs (72 barrows and 72 gilts) were utilized in six treatments with six pens each to evaluate four levels of daily porcine somatotropin (pST) injections (0, 1, 3, or 5 mg/d) in combination with diets containing 13 or 16% crude protein (CP). One randomly selected pig from each pen was slaughtered when it reached a weight between 230 and 240 lb. Daily feed intake (ADFI), tenth rib backfat, and estimated percentage of lean pork were reduced in pigs fed the 13% CP diet and injected with 3 mg/d pST compared to pigs fed the same diet and injected daily with a placebo. Feed intake was reduced in pigs fed the 16% CP diet and injected daily with 3 and 5 mg/d pST. Improvement in feed conversion (F/G), tenth rib backfat, and estimated percentage lean pork occurred when pigs fed the 16% CP diet were injected with 1 mg/d, with greater improvements occurring at the 3 and 5 mg/d levels of pST. The improvement in F/G and the greater magnitude of response observed in pigs fed 16% CP diets compared to the response of pigs fed the 13% CP diet indicate that both the performance and carcass characteristics of pigs injected with pST are dependent on the dietary CP content

Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor

Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions—both therapeutic and hallucinogenic—are not understood, although activation of the 5-HT2A serotonin receptor (HTR2A) is key. To gain molecular insights into psychedelic actions, we determined the active-state structure of HTR2A bound to 25-CN-NBOH—a prototypical hallucinogen—in complex with an engineered Gαq heterotrimer by cryoelectron microscopy (cryo-EM). We also obtained the X-ray crystal structures of HTR2A complexed with the arrestin-biased ligand LSD or the inverse agonist methiothepin. Comparisons of these structures reveal determinants responsible for HTR2A-Gαq protein interactions as well as the conformational rearrangements involved in active-state transitions. Given the potential therapeutic actions of hallucinogens, these findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders. © 2020 Elsevier Inc.; Roth et al. reveal structurally how psychedelics, including LSD, psilocin, mescaline, and various N-BOH analogs, mediate their therapeutic and hallucinogenic effects by binding to and activating their molecular target, the serotonin (5-HT) 2A receptor coupled with G-protein Gαq

‘It’s Kinda Punishment’: Tandem Logics and Penultimate Power in the Penal Voluntary Sector for Canadian Youth

This paper draws on original empirical research in Ontario, Canada which analyses penal voluntary sector practice with youth in conflict with the law. I illustrate how youth penal voluntary sector practice (YPVS) operates alongside, or in tandem with the statutory criminal justice system. I argue that examining the PVS and the statutory criminal justice system simultaneously, or in tandem, provides fuller understandings of PVS inclusionary (and exclusionary) control practices (Tomczak and Thompson 2017). I introduce the concept of penultimate power, which demonstrates the ability of PVS workers to trigger criminal justice system response toward a young person in conflict with the law. My novel concepts of tandem logics and penultimate power are useful for understanding PVS practice, explaining how seemingly contradictory approaches across state and ‘community’ organizations not only co-exist, but depend upon the tandem relationship between the PVS and the statutory criminal justice system

Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD

Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT2A serotonin receptor (HTR2A), the 5-HT2B serotonin receptor (HTR2B) has been used as a model receptor to study the activation mechanisms of psychedelic drugs due to its high expression and similarity to HTR2A. In this study, we determined the cryo-EM structures of LSD-bound HTR2B in the transducer-free, Gq-protein-coupled, and β-arrestin-1-coupled states. These structures provide distinct signaling snapshots of LSD's action, ranging from the transducer-free, partially active state to the transducer-coupled, fully active states. Insights from this study will both provide comprehensive molecular insights into the signaling mechanisms of the prototypical psychedelic LSD and accelerate the discovery of novel psychedelic drugs

Tratamento conservativo e cirúrgico em 22 ruminantes com fraturas em membros

O objetivo do presente trabalho foi relatar os principais locais de fraturas em membros de 22 ruminantes e determinar a eficiência dos tratamentos utilizados. Foram incluídos no estudo oito caprinos, oito ovinos e seis bovinos Em casos de fraturas distais, o tratamento conservativo com imobilização foi o método de eleição. Em casos de fraturas proximais e fraturas expostas de metatarso ou metacarpo, os ruminantes foram tratados cirurgicamente. Observou-se maior frequência de fraturas envolvendo o metacarpo ou metatarso (54,5%), seguido por fraturas de tíbia (22,7%), fêmur (9%) e casos isolados de fraturas de falange medial, úmero, rádio e ulna (4,5% cada). O índice de recuperação total alcançou 95,4%. A imobilização com gesso associada à tala de Thomas, ou apenas com talas de madeira em animais jovens, foi eficiente na redução de fraturas de metacarpo, metatarso, tíbia, úmero e rádio nos ruminantes tratados. Enquanto no caso de fratura de falange medial, a imobilização com uso apenas de gesso foi suficiente para proporcionar reparação óssea adequada. A fixação esquelética externa ou interna deve ser considerada uma opção no tratamento de fraturas metacárpicas, metatársicas, tibiais e femorais em ruminantes, principalmente quando o animal for de baixo peso corporal

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected