Evaluation of self-administered antigen testing in a college setting.

BACKGROUND: The objective of our investigation was to better understand barriers to implementation of self-administered antigen screening testing for SARS-CoV-2 at institutions of higher education (IHE). METHODS: Using the Quidel QuickVue At-Home COVID-19 Test, 1347 IHE students and staff were asked to test twice weekly for seven weeks. We assessed seroconversion using baseline and endline serum specimens. Online surveys assessed acceptability. RESULTS: Participants reported 9971 self-administered antigen test results. Among participants who were not antibody positive at baseline, the median number of tests reported was eight. Among 324 participants seronegative at baseline, with endline antibody results and ≥ 1 self-administered antigen test results, there were five COVID-19 infections; only one was detected by self-administered antigen test (sensitivity = 20%). Acceptability of self-administered antigen tests was high. CONCLUSIONS: Twice-weekly serial self-administered antigen testing in a low prevalence period had low utility in this investigation. Issues of testing fatigue will be important to address in future testing strategies.

Isolation, Loneliness and Aloneness in the Age of Covid-19: Reflections on Clinical Experiences.

The Covid-19 pandemic brought a heightened fear of death and illness, and increased experiences of isolation, loneliness and aloneness. In this article we describe clinical experiences of psychotherapists in Argentina, the UK and Germany in order to explore how the impacts of the pandemic are variously felt and mediated by inner resources. We explore the capacity to relate internally to good experiences of infancy and a secure internal world, and the risks of loneliness, and interpersonal and intrapsychic withdrawal, that lead to vulnerability in patients and therapists. We contrast instances where psychotherapy in response to increased fears of death, infection and isolation is facilitative of change and growth, with situations where perverse, destructive or defensive relating predominate. We ask if we are witnessing and, through our therapeutic activities, contributing to the emergence of new ways of understanding the internal conflicts of this Covid-19 age, and tentatively identify some key emerging themes; the capacity for facilitative interactions and change; identifications with the powerful virus; an increase in paranoid anxieties and the potential for a more considerate, 'care-full' way of relating.

Point-of-Care Antigen Test for SARS-CoV-2 in Asymptomatic College Students.

We used the BinaxNOW COVID-19 Ag Card to screen 1,540 asymptomatic college students for severe acute respiratory syndrome coronavirus 2 in a low-prevalence setting. Compared with reverse transcription PCR, BinaxNOW showed 20% overall sensitivity; among participants with culturable virus, sensitivity was 60%. BinaxNOW provides point-of-care screening but misses many infections.

Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions.

OBJECTIVE: Infantile spasms may evolve into persistent epilepsies including Lennox-Gastaut syndrome. We compared adult epilepsy outcomes in models of infantile spasms due to structural etiology (multiple-hit model) or focal cortical inflammation and determined the anti-epileptogenic effects of pulse-rapamycin, previously shown to stop spasms in multiple-hit rats. METHODS: Spasms were induced in 3-day-old male rats via right intracerebral doxorubicin/lipopolysaccharide (multiple-hit model) infusions. Controls and sham rats were used. Separate multiple-hit rats received pulse-rapamycin or vehicle intraperitoneally between postnatal days 4 and 6. In adult mice, video-EEG (electroencephalography) scoring for seizures and sleep and histology were done blinded to treatment. RESULTS: Motor-type seizures developed in 66.7% of multiple-hit rats, usually from sleep, but were reduced in the pulse-rapamycin-treated group (20%, p = .043 vs multiple-hit) and rare in other groups (0-9.1%, p < .05 vs multiple-hit). Spike-and-wave bursts had a slower frequency in multiple-hit rats (5.4-5.8Hz) than in the other groups (7.6-8.3Hz) (p < .05); pulse rapamycin had no effect on the hourly spike-and-wave burst rates in adulthood. Rapamycin, however, reduced the time spent in slow-wave-sleep (17.2%), which was increased in multiple-hit rats (71.6%, p = .003). Sham rats spent more time in wakefulness (43.7%) compared to controls (30.6%, p = .043). Multiple-hit rats, with or without rapamycin treatment, had right more than left corticohippocampal, basal ganglia lesions. There was no macroscopic pathology in the other groups. SIGNIFICANCE: Structural corticohippocampal/basal ganglia lesions increase the risk for post-infantile spasms epilepsy, Lennox-Gastaut syndrome features, and sleep dysregulation. Pulse rapamycin treatment for infantile spasms has anti-epileptogenic effects, despite the structural lesions, and decreases the time spent in slow wave sleep.

The effectiveness of psychoanalytic/psychodynamic psychotherapy for reducing suicide attempts and self-harm: systematic review and meta-analysis.

BACKGROUND: Preventing suicide and self-harm is a global health priority. Although there is a growing evidence base for the effectiveness of psychoanalytic and psychodynamic psychotherapies for a range of disorders, to date there has been no systematic review of its effectiveness in reducing suicidal and self-harming behaviours.AimsTo systematically review randomised controlled trials of psychoanalytic and psychodynamic psychotherapies for suicidal attempts and self-harm. METHOD: We searched PubMed, PsycINFO, Psycharticles, CINAHL, EMBASE and the Cochrane Central Register of Controlled Trials for randomise controlled trials of psychoanalytic and psychodynamic psychotherapies for reducing suicide attempts and self-harm. RESULTS: Twelve trials (17 articles) were included in the meta-analyses. Psychoanalytic and psychodynamic therapies were effective in reducing the number of patients attempting suicide (pooled odds ratio, 0.469; 95% CI 0.274-0.804). We found some evidence for significantly reduced repetition of self-harm at 6-month but not 12-month follow-up. Significant treatment effects were also found for improvements in psychosocial functioning and reduction in number of hospital admissions. CONCLUSIONS: Psychoanalytic and psychodynamic psychotherapies are indicated to be effective in reducing suicidal behaviour and to have short-term effectiveness in reducing self-harm. They can also be beneficial in improving psychosocial well-being. However, the small number of trials and moderate quality of the evidence means further high-quality trials are needed to confirm our findings and to identity which specific components of the psychotherapies are effective.Declaration of interestNone.

CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms.

OBJECTIVE: Infantile spasms (IS) have poor outcomes and limited treatment options, including vigabatrin, a γ-aminobutyric acid (GABA) aminotransferase inactivator. Vigabatrin has been associated with retinal toxicity. A high affinity vigabatrin analogue (CPP-115; Catalyst Pharmaceutical Partners, Inc., Coral Gables, FL, U.S.A.) has shown lower risk of retinal toxicity. Here, we test the efficacy of CPP-115 in reducing spasms and its tolerability in the multiple-hit rat model of IS, in which daily vigabatrin reduced spasms for only one day, but was not well tolerated. METHODS: Male rats were treated with the protocol of the multiple-hit model of IS on postnatal day 3 (PN3). Using a randomized, blinded, vehicle-controlled, dose-response study design, CPP-115 (0.1, 1, or 5 mg/kg intraperitoneally [i.p.]) or vehicle was given daily (PN4-12) or as a single injection (PN7) after spasm onset. Intermittent video- or video-electroencephalography (EEG) monitoring was done. Secondary end points included the following: daily weights, survival, performance on open field activity, surface righting time, and negative geotaxis (PN3-20), horizontal bar (PN13-20), and Barnes maze (PN16-19). Statistics used a linear mixed model of raw or normalized log-transformed data, taking into account the repeated observations on each animal. RESULTS: The lower CPP-115 doses (0.1-1 mg/kg/day, PN4-12) reduced spasms between PN6 and 7 without increasing mortality. CPP-115 at 5 mg/kg/day (PN4-12) reduced spasms earlier (PN5), but was eventually lethal. A single CPP-115 injection (1 mg/kg, i.p.) decreased electroclinical spasms acutely but transiently. CPP-115 transiently improved the probability to >50% reduction of spasms, but did not accelerate spasm cessation. CPP-115 did not alter neurodevelopmental outcomes or visuospatial learning. SIGNIFICANCE: We provide proof-of-concept evidence that CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of IS at considerably lower and better tolerated doses than vigabatrin did in our previous studies. Further optimization of the treatment protocol is needed. CPP-115 may be a promising new candidate treatment for IS with better tolerability than vigabatrin.

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer.

Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development.

pH-dependent modulation of voltage gating in connexin45 homotypic and connexin45/connexin43 heterotypic gap junctions.

Intracellular pH (pH(i)) can change during physiological and pathological conditions causing significant changes of electrical and metabolic cell-cell communication through gap junction (GJ) channels. In HeLa cells expressing wild-type connexin45 (Cx45) as well as Cx45 and Cx43 tagged with EGFP, we examined how pH(i) affects junctional conductance (g(j)) and g(j) dependence on transjunctional voltage (V(j)). To characterize V(j) gating, we fit the g(j)-V(j) relation using a stochastic four-state model containing one V(j)-sensitive gate in each apposed hemichannel (aHC); aHC open probability was a Boltzmann function of the fraction of V(j) across it. Using the model, we estimated gating parameters characterizing sensitivity to V(j) and number of functional channels. In homotypic Cx45 and heterotypic Cx45/Cx43-EGFP GJs, pH(i) changes from 7.2 to approximately 8.0 shifted g(j)-V(j) dependence of Cx45 aHCs along the V(j) axis resulting in increased probability of GJ channels being in the fully open state without change in the slope of g(j) dependence on V(j). In contrast, acidification shifted g(j)-V(j) dependence in the opposite direction, reducing open probability; acidification also reduced the number of functional channels. Correlation between the number of channels in Cx45-EGFP GJs and maximal g(j) achieved under alkaline conditions showed that only approximately 4% of channels were functional. The acid dissociation constant (pK(a)) of g(j)-pH(i) dependence of Cx45/Cx45 GJs was approximately 7. The pK(a) of heterotypic Cx45/Cx43-EGFP GJs was lower, approximately 6.7, between the pK(a)s of Cx45 and Cx43-EGFP (approximately 6.5) homotypic GJs. In summary, pH(i) significantly modulates junctional conductance of Cx45 by affecting both V(j) gating and number of functional channels.

Factors that influence food choices in secondary school canteens: a qualitative study of pupil and staff perspectives.

Background: Adolescence is recognised as a period of nutritional vulnerability, with evidence indicating that United Kingdom adolescents have suboptimal dietary intakes with many failing to meet dietary recommendations. Additionally, adolescence is a time of transition when they become more independent in their dietary choices and begin to develop their own sense of autonomy and are less reliant on their parent's guidance, which is reported to lead to less favourable dietary behaviours. Reducing the prevalence of poor dietary intakes and the associated negative health consequences among this population is a public health priority and schools represent an important setting to promote positive dietary behaviours. The aim of this school-based study was to explore the factors and barriers which influence food choices within the school canteen and to identify feasible strategies to promote positive dietary behaviours within this setting. Methods: Thirteen focus groups with 86 pupils in Year 8 (n = 37; aged 11-12 years) and Year 9 (n = 49; aged 12-13 years) in six secondary schools across Northern Ireland, United Kingdom were conducted. Additionally, one-to-one virtual interviews were conducted with 29 school staff [principals/vice-principals (n = 4); teachers (n = 17); and caterers (n = 7)] across 17 secondary schools and an Education Authority (EA) senior staff member (n = 1). Focus groups and interviews were audio-recorded, transcribed, and analysed following an inductive thematic approach. Results: Using the ecological framework, multiple factors were identified which influenced pupils' selection of food in the school canteen at the individual (e.g., time/convenience), social (e.g., peer influence), physical (e.g., food/beverage placement), and macro environment (e.g., food provision) level. Suggestions for improvement of food choices were also identified at each ecological level: individual (e.g., rewards), social (e.g., pupil-led initiatives), physical (e.g., labelling), and macro environment (e.g., whole-school approaches). Conclusion: Low-cost and non-labour intensive practical strategies could be employed, including menu and labelling strategies, placement of foods, reviewing pricing policies and whole-school initiatives in developing future dietary interventions to positively enhance adolescents' food choices in secondary schools.

Toward a roadmap for space-based observations of the land sector for the UNFCCC global stocktake.

Space-based remote sensing can make an important contribution toward monitoring greenhouse gas emissions and removals from the agriculture, forestry, and other land use (AFOLU) sector, and to understanding and addressing human-caused climate change through the UNFCCC Paris Agreement. Space agencies have begun to coordinate their efforts to identify needs, collect and harmonize available data and efforts, and plan and maintain a long-term roadmap for observations. International cooperation is crucial in developing and realizing the roadmap, and the Committee on Earth Observation Satellites (CEOS) is a key coordinating driver of this effort. Here, we first identify the data and information that will be useful to support the global stocktake (GST) of the Paris Agreement. Then, the paper explains how existing and planned space-based capabilities and products can be used and combined, particularly in the land use sector, and provides a workflow for their harmonization and contribution to greenhouse gas inventories and assessments at the national and global level.

Psychoanalytic understanding of the request for assisted suicide.

The legalisation of assisted dying, including euthanasia and physician assisted suicide, is increasing in countries across the world and constitutes a key contemporary debate, reflecting social changes, in which two views of suicide conflict; that (1) rational reasons justify assisted suicide, providing dignity and control of terminal illness and (2) suicidal wishes are driven by unconscious and disturbing internal conflicts. In this paper we explore the unconscious motives and meanings of requests for assisted suicide. Although there is a paucity of psychoanalytic literature on the subject, and an absence of practice examples, we make two links, firstly, with the literature of palliative and end of life care, and, secondly, with psychoanalytic understanding of suicide, in order to develop the view that unconscious factors are crucial to understanding requests for assisted suicide. We provide an illustrative case example of psychodynamic psychotherapy with a 94-year-old woman, drawing out theoretical and practice implications. We show that unconscious factors and motives lie behind apparently rational requests for assisted suicide, and attention to these through psychoanalytically informed treatment can bring about therapeutic change.

A pulse rapamycin therapy for infantile spasms and associated cognitive decline.

Infantile spasms are seizures manifesting within a spectrum of epileptic encephalopathies of infancy that often lead to cognitive impairment. Their current therapies, including adrenocorticotropic hormone (ACTH), high dose steroids, or vigabatrin, are not always effective and may be associated with serious side effects. Overactivation of the TORC1 complex of the mTOR pathway is implicated in the pathogenesis of certain genetic and acquired disorders that are linked with infantile spasms, like tuberous sclerosis. Here, we tested the therapeutic potential of rapamycin, a TORC1 inhibitor, as a potential treatment for infantile spasms in the multiple-hit rat model of ACTH-refractory symptomatic infantile spasms, which is not linked to tuberous sclerosis. Rapamycin or vehicle was given after spasms appeared. Their effects on spasms, other seizures, performance in Barnes maze, and expression of the phosphorylated S6 ribosomal protein (pS6: a TORC1 target) in the cortex, using immunofluorescence, were compared. Rapamycin suppressed spasms dose-dependently and improved visuospatial learning, although it did not reduce the frequency of other emerging seizures. High-dose pulse rapamycin effected acute and sustained suppression of spasms and improved cognitive outcome, without significant side effects. Therapeutically effective rapamycin doses normalized the pS6 expression, which was increased in perilesional cortical regions of pups with spasms. These findings support that pathological overactivation of TORC1 may be implicated in the pathogenesis of infantile spasms, including those that are not linked to tuberous sclerosis. Furthermore, a high-dose, pulse rapamycin treatment is a promising, well tolerated and disease-modifying new therapy for infantile spasms, including those refractory to ACTH.

STEP regulation of seizure thresholds in the hippocampus.

PURPOSE: To investigate whether striatal enriched protein tyrosine phosphatase (STEP) influences ictogenesis. METHODS: STEP knockout mice were compared to wild-type (WT) mice in pilocarpine-induced seizures. Hippocampal slices were also prepared from these two mouse populations, allowing the examination of ictal-like stimulation in these slices using calcium imaging and electrophysiologic recordings. KEY FINDINGS: To examine seizure thresholds, increasing doses of pilocarpine were administered to adult mice and seizures were scored behaviorally. Significantly fewer STEP knockout mice developed seizures that progressed to the stage of status epilepticus compared to WT mice. To examine potential differences in neural circuits that might account for this finding, seizure-like activity was induced in hippocampal slices. Electrical stimulation of the hippocampal-entorhinal cortex pathway in STEP knockout mice resulted in less activation of the dentate gyrus granule cell layer (GCL), but greater activation of the hilus in STEP knockouts, compared with heterozygous slices. SIGNIFICANCE: STEP deficiency is associated with higher seizure thresholds. The locus of these effects appears to include the dentate gyrus granule cell layer and hilus.

Altered GABA signaling in early life epilepsies.

The incidence of seizures is particularly high in the early ages of life. The immaturity of inhibitory systems, such as GABA, during normal brain development and its further dysregulation under pathological conditions that predispose to seizures have been speculated to play a major role in facilitating seizures. Seizures can further impair or disrupt GABA(A) signaling by reshuffling the subunit composition of its receptors or causing aberrant reappearance of depolarizing or hyperpolarizing GABA(A) receptor currents. Such effects may not result in epileptogenesis as frequently as they do in adults. Given the central role of GABA(A) signaling in brain function and development, perturbation of its physiological role may interfere with neuronal morphology, differentiation, and connectivity, manifesting as cognitive or neurodevelopmental deficits. The current GABAergic antiepileptic drugs, while often effective for adults, are not always capable of stopping seizures and preventing their sequelae in neonates. Recent studies have explored the therapeutic potential of chloride cotransporter inhibitors, such as bumetanide, as adjunctive therapies of neonatal seizures. However, more needs to be known so as to develop therapies capable of stopping seizures while preserving the age- and sex-appropriate development of the brain.

Legacy effects override soil properties for CO2 and N2O but not CH4 emissions following digestate application to soil.

The application of organic materials to soil can recycle nutrients and increase organic matter in agricultural lands. Digestate can be used as a nutrient source for crop production but it has also been shown to stimulate greenhouse gas (GHG) emissions from amended soils. While edaphic factors, such as soil texture and pH, have been shown to be strong determinants of soil GHG fluxes, the impact of the legacy of previous management practices is less well understood. Here we aim to investigate the impact of such legacy effects and to contrast them against soil properties to identify the key determinants of soil GHG fluxes following digestate application. Soil from an already established field experiment was used to set up a pot experiment, to evaluate N2O, CH4 and CO2 fluxes from cattle-slurry-digestate amended soils. The soil had been treated with farmyard manure, green manure or synthetic N-fertilizer, 18 months before the pot experiment was set up. Following homogenization and a preincubation stage, digestate was added at a concentration of 250 kg total N/ha eq. Soil GHG fluxes were then sampled over a 64 day period. The digestate stimulated emissions of the three GHGs compared to controls. The legacy of previous soil management was found to be a key determinant of CO2 and N2O flux while edaphic variables did not have a significant effect across the range of variables included in this experiment. Conversely, edaphic variables, in particular texture, were the main determinant of CH4 flux from soil following digestate application. Results demonstrate that edaphic factors and current soil management regime alone are not effective predictors of soil GHG flux response following digestate application. Knowledge of the site management in terms of organic amendments is required to make robust predictions of the likely soil GHG flux response following digestate application to soil.

Maytree: A respite center for the suicidal: an evaluation.

This paper evaluates the contribution to suicide prevention made by an innovative project, Maytree, a respite center for the suicidal. Maytree offers a distinctive brief period of sanctuary for four nights for suicidal people; within this limited time it aims to provide opportunities through talking, reflecting, and relaxing for reducing the intense feelings that lead to suicidal behavior. The focus of this paper is on evaluating the first 3 years of Maytree's operation, exploring how Maytree works, and its effects on the people who stay there as "guests". This shows that Maytree reaches people who are at significant risk of suicide. Guests report both short term relief and longer term benefits. These changes are understood, through applying crisis intervention theory, as being generated by the opportunities for change in the Maytree approach. Thus, there is the potential for a benign cycle to be established. Maytree's model is different from that of mainstream, statutory services; we conclude that Maytree complements these services and also challenges the values and frameworks of statutory provision in the field of suicide prevention.

The ability of the Lauge-Hansen classification to predict ligament injury and mechanism in ankle fractures: an MRI study.

OBJECTIVES: The Lauge-Hansen classification system was designed to predict the mechanism and ligament injury patterns of ankle fractures on the basis of x-rays. The purpose of this study was to evaluate the accuracy of these predicted injury sequences using magnetic resonance imaging (MRI) in a series of patients with ankle fractures. DESIGN: Retrospective cohort. SETTING: Two university level 1 trauma centers. PATIENTS: Fifty-nine patients with operative ankle fractures who were evaluated with both x-ray and MRI were included. INTERVENTION: All patients had a standard 3-view ankle x-ray series before fracture reduction, followed by an MRI. All plain x-rays were assigned to a Lauge-Hansen category by an experienced orthopedic traumatologist. MRI studies were subsequently read by an MRI musculoskeletal radiologist for the integrity of the ankle ligaments. MAIN OUTCOME MEASUREMENTS: After evaluation of the x-rays, fractures were classified according to the system of Lauge-Hansen, and the predicted presence, sequence, and mechanism of injury was determined. These were then compared to the actual injured structures on MRI in each case, and the ability of the Lauge-Hansen system to accurately predict the complete injury pattern was determined for the entire cohort. RESULTS: Average patient age was 59 (range: 18 to 84) years. Of the 59 ankle fractures evaluated, 37 (63%) were classified as supination external rotation, 11 (19%) were pronation external rotation, 1 (2%) was supination adduction, and 10 (17%) were not classifiable on the basis of the Lauge-Hansen system. Of the 49 fractures that fit into Lauge-Hansen categories, 26 (53%) had patterns of ligamentous injury and fracture morphology that did not coincide with the Lauge-Hansen predictions. A common fracture pattern was observed in 8 of the 10 unclassifiable fractures, which included a high spiral fracture of the fibula, vertical shear fracture of the medial malleolus, posterior malleolar fracture, and complete tears of the anterior-inferior tibiofibular ligament and the interosseous membrane. In addition, over 65% of patients in this series had complete ligamentous injury and a fracture of the malleolus to which the ligament attaches. CONCLUSIONS: These results demonstrate that the Lauge-Hansen classification system may have some limitations as a predictor of the mechanism of injury and the presence of soft-tissue damage associated with ankle fractures. The identification of a novel pattern of ankle fracture also illustrates how the system fails to describe all possible fracture patterns. For these reasons, we recommend that the Lauge-Hansen system be used only as a guide in the diagnosis and management of ankle fractures and not solely relied upon for treatment decisions. Although the exact clinical implications of the variety of ligamentous injuries observed on MRI are yet to be determined, this technique may be useful in individual cases in which doubt about joint stability and soft-tissue integrity exists. Additionally, MRI may be helpful in planning surgical approaches in atypical fractures in which injury patterns are less predictable solely on the basis of x-ray.

Malreduction of the tibiofibular syndesmosis in ankle fractures.

BACKGROUND: Diagnosis and reduction of syndesmosis injuries in ankle fractures can be challenging. Previous studies have demonstrated that standard radiographic measurements used to evaluate the integrity of the syndesmosis are inaccurate. The purpose of this study was to determine the adequacy of standard postoperative radiographic measurements in assessing syndesmotic reduction compared to CT and to determine the prevalence of postoperative syndesmotic malreduction in a patient cohort. METHODS: Twenty-five patients with ankle fractures and syndesmotic instability who had open reduction and syndesmotic fixation were evaluated. All patients had a standard radiographic series postoperatively followed by a CT scan. Radiographic measurements were made by three observers to determine the tibiofibular relationship. Axial CT scan images were judged for quality of reduction of the syndesmosis by measuring the distance between the fibula and the anterior and posterior facets of the incisura. Differences between the anterior and posterior measurements of more than 2 mm were considered incongruous. RESULTS: Six patients (24%) had evidence of postoperative diastasis using the radiographic criteria, four of whom had evidence of malreduction on postoperative CT scan. Conversely, 13 patients (52%) had incongruity of the fibula within the incisura on CT scan (average 3.6 mm, range 2.0 to 8.0 mm), only four of whom had one or more abnormal radiographic measurements. In 10 (77%) of the 13 malreductions seen on CT scan, the posterior measurement was greater, indicating that internal rotation or anterior translation of the fibula may have occurred. Sensitivity of radiographs was 31% and the specificity was 83% compared to CT. CONCLUSIONS: Many syndesmoses were malreduced on CT scan but went undetected by plain radiographs. Radiographic measurements did not accurately reflect the status of the distal tibiofibular joint in this series of ankle fractures. Furthermore, postreduction radiographic measurements were inaccurate for assessing the quality of the reduction. Although we did not seek to correlate functional outcomes, the known morbidity of postoperative syndesmotic malreduction should lead to heightened vigilance for assessing accurate syndesmosis reduction intraoperatively.

Assessing and engaging suicidal teenagers in psychoanalytic psychotherapy: a case consultation.

Assessing and engaging suicidal adolescents in psychoanalytic psychotherapy is filled with complexity and stress, but offers a potential for lasting suicide prevention. This study provides a detailed account of the initial psychotherapy sessions with a suicidal teenager, drawing extensively on the comprehensive notes taken by the therapist. Four discussants were invited to provide their perspectives as to how they would assess the main factors in the case and from this to provide a brief commentary for their own perspectives. This study concludes with a discussion of the differences and commonalities between the various contributions.

A novel glucokinase activator modulates pancreatic islet and hepatocyte function.

The glucose-sensing enzyme glucokinase (GK) plays a key role in glucose metabolism. We report here the effects of a novel glucokinase activator, LY2121260. The activator enhanced GK activity via binding to the allosteric site located in the hinge region of the enzyme. LY2121260 stimulated insulin secretion in a glucose-dependent manner in pancreatic beta-cells and increased glucose use in rat hepatocytes. In addition, incubation of beta-cells with the GK activator resulted in increased GK protein levels, suggesting that enhanced insulin secretion on chronic treatment with a GK activator may be due to not only changed enzyme kinetics but also elevated enzyme levels. Animals treated with LY2121260 showed an improved glucose tolerance after oral glucose challenge. These results support the concept that GK activators represent a new class of compounds that increase both insulin secretion and hepatic glucose use and in doing so may prove to be effective agents for the control of blood glucose levels in patients with type 2 diabetes.