Recognizing thyrotoxicosis in a patient with bipolar mania: a case report

<p>Abstract</p> <p>Background</p> <p>A thyroid stimulating hormone level is commonly measured in patients presenting with symptoms of mania in order to rule out an underlying general medical condition such as hyperthyroidism or thyrotoxicosis. Indeed, many cases have been reported in which a patient is initially treated for bipolar mania, but is later found to have a thyroid condition. Several case reports have noted the development of a thyroid condition in bipolar patients either on lithium maintenance treatment or recently on lithium treatment.</p> <p>Case presentation</p> <p>We review a case in which a patient with a long history of bipolar disorder presents with comorbid hyperthyroidism and bipolar mania after recent discontinuation of lithium treatment.</p> <p>Conclusion</p> <p>Physicians should consider a comorbid hyperthyroidism in bipolar manic patients only partially responsive to standard care treatment with a mood stabilizer and antipsychotic.</p

Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled activation subunits, while the DA was modeled using uncoupled activation subunits. Implementations of DA with coupled subunits, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable - allowing an easy and efficient DA implementation. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur

Probing electron-phonon interactions away from the Fermi level with resonant inelastic x-ray scattering

Interactions between electrons and lattice vibrations are responsible for a wide range of material properties and applications. Recently, there has been considerable interest in the development of resonant inelastic x-ray scattering (RIXS) as a tool for measuring electron-phonon ( e -ph) interactions. Here, we demonstrate the ability of RIXS to probe the interaction between phonons and specific electronic states both near to, and away from, the Fermi level. We perform carbon K -edge RIXS measurements on graphite, tuning the incident x-ray energy to separately probe the interactions of the π ∗ and σ ∗ electronic states. Our high-resolution data reveal detailed structure in the multiphonon RIXS features that directly encodes the momentum dependence of the e -ph interaction strength. We develop a Green’s-function method to model this structure, which naturally accounts for the phonon and interaction-strength dispersions, as well as the mixing of phonon momenta in the intermediate state. This model shows that the differences between the spectra can be fully explained by contrasting trends of the e -ph interaction through the Brillouin zone, being concentrated at the Γ and K points for the π ∗ states while being significant at all momenta for the σ ∗ states. Our results advance the interpretation of phonon excitations in RIXS and extend its applicability as a probe of e -ph interactions to a new range of out-of-equilibrium situations

Association of angiotensin-converting enzyme inhibitor therapy and comorbidity in diabetes: results from the Vermont diabetes information system

<p>Abstract</p> <p>Background</p> <p>Angiotensin converting enzyme inhibitors (ACE inhibitors) reduce peripheral vascular resistance via blockage of angiotensin converting enzyme (ACE). ACE inhibitors are commonly used to treat congestive heart failure and high blood pressure, but other effects have been reported. In this study, we explored the association between ACE inhibitor therapy and the prevalence of comorbid conditions in adults with diabetes</p> <p>Methods</p> <p>We surveyed 1003 adults with diabetes randomly selected from community practices. Patients were interviewed at home and self-reported their personal and clinical characteristics including comorbidity. Current medications were obtained by direct observation of medication containers. We built logistic regression models with the history of comorbidities as the outcome variable and the current use of ACE inhibitors as the primary predictor variable. We adjusted for possible confounding by social (age, sex, alcohol drinking, cigarette smoking) and clinical factors (systolic blood pressure, body mass index (BMI), glycosolated hemoglobin (A1C), number of comorbid conditions, and number of prescription medications).</p> <p>Results</p> <p>ACE users reported a history of any cancer (except the non-life-threatening skin cancers) less frequently than non-users (10% <it>vs</it>. 15%; odd ratio = 0.59; 95% confidence interval [0.39, 0.89]; <it>P </it>= 0.01); and a history of stomach ulcers or peptic ulcer disease less frequently than non-users (12% <it>vs</it>. 16%, odd ratio = 0.70, [0.49, 1.01], <it>P </it>= 0.06). After correcting for potential confounders, ACE inhibitors remained significantly inversely associated with a personal history of cancer (odds ratio = 0.59, [0.39, 0.89]; <it>P </it>= 0.01) and peptic ulcer disease (odd ratio = 0.68, [0.46, 1.00], <it>P </it>= 0.05).</p> <p>Conclusion</p> <p>ACE inhibitor use is associated with a lower likelihood of a history of cancer and peptic ulcers in patients with diabetes. These findings are limited by the cross sectional study design, self-report of comorbid diagnoses, and lack of information on the timing and duration of ACE inhibitor use. Further research is needed to confirm these associations and understand their mechanisms.</p

Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48

Dysregulated mitochondrial function is a hallmark of immune-mediated inflammatory diseases. Cytochrome c oxidase (CcO), which mediates the rate-limiting step in mitochondrial respiration, is remodeled during development and in response to changes of oxygen availability, but there has been little study of CcO remodeling during inflammation. Here, we describe an elegant molecular switch mediated by the bifunctional transcript C15orf48, which orchestrates the substitution of the CcO subunit NDUFA4 by its paralog C15ORF48 in primary macrophages. Expression of C15orf48 is a conserved response to inflammatory signals and occurs in many immune-related pathologies. In rheumatoid arthritis, C15orf48 mRNA is elevated in peripheral monocytes and proinflammatory synovial tissue macrophages, and its expression positively correlates with disease severity and declines in remission. C15orf48 is also expressed by pathogenic macrophages in severe coronavirus disease 2019 (COVID-19). Study of a rare metabolic disease syndrome provides evidence that loss of the NDUFA4 subunit supports proinflammatory macrophage functions

Supporting dynamic change detection: using the right tool for the task

Detecting task-relevant changes in a visual scene is necessary for successfully monitoring and managing dynamic command and control situations. Change blindness—the failure to notice visual changes—is an important source of human error. Change History EXplicit (CHEX) is a tool developed to aid change detection and maintain situation awareness; and in the current study we test the generality of its ability to facilitate the detection of changes when this subtask is embedded within a broader dynamic decision-making task. A multitasking air-warfare simulation required participants to perform radar-based subtasks, for which change detection was a necessary aspect of the higher-order goal of protecting one’s own ship. In this task, however, CHEX rendered the operator even more vulnerable to attentional failures in change detection and increased perceived workload. Such support was only effective when participants performed a change detection task without concurrent subtasks. Results are interpreted in terms of the NSEEV model of attention behavior (Steelman, McCarley, & Wickens, Hum. Factors 53:142–153, 2011; J. Exp. Psychol. Appl. 19:403–419, 2013), and suggest that decision aids for use in multitasking contexts must be designed to fit within the available workload capacity of the user so that they may truly augment cognition

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector.

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies

Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

<p>Abstract</p> <p>Background</p> <p>In idiopathic pulmonary arterial hypertension (IPAH), peripheral airway obstruction is frequent. This is partially attributed to the mediator dysbalance, particularly an excess of endothelin-1 (ET-1), to increased pulmonary vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor antagonist) improves pulmonary hemodynamics, exercise limitation, and disease severity in IPAH. We hypothesized that bosentan might affect airway obstruction.</p> <p>Methods</p> <p>In 32 IPAH-patients (19 female, WHO functional class II (n = 10), III (n = 22); (data presented as mean ± standard deviation) pulmonary vascular resistance (11 ± 5 Wood units), lung function, 6 minute walk test (6-MWT; 364 ± 363.7 (range 179.0-627.0) m), systolic pulmonary artery pressure, sPAP, 79 ± 19 mmHg), and NT-proBNP serum levels (1427 ± 2162.7 (range 59.3-10342.0) ng/L) were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice per day).</p> <p>Results and Discussion</p> <p>At baseline, maximal expiratory flow at 50 and 25% vital capacity were reduced to 65 ± 25 and 45 ± 24% predicted. Total lung capacity was 95.6 ± 12.5% predicted and residual volume was 109 ± 21.4% predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 ± 19 and 53 ± 69 m, respectively; p < 0.01; whereas sPAP decreased by 7 ± 14 and 10 ± 19 mmHg, respectively; p < 0.05. NT-proBNP serum levels tended to be reduced by 123 ± 327 and by 529 ± 1942 ng/L; p = 0.11). There was no difference in expiratory flows or lung volumes during 3 and 12 months.</p> <p>Conclusion</p> <p>This study gives first evidence in IPAH, that during long-term bosentan, improvement of hemodynamics, functional parameters or serum biomarker occur independently from persisting peripheral airway obstruction.</p