184 research outputs found

    Corticosteroid-induced manic and/or psychotic symptoms: a systematic review

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    Introduction: Given their immunosuppressive and anti-inflammatory properties, corticosteroids are widely used. However, corticosteroid-induced psychiatric effects are deeply concerning, since they can be severe and require accurate differential diagnosis from primary psychiatric disorders. Among corticosteroid-induced psychiatric symptoms, what kind of patients under corticosteroids develop manic and/or psychotic symptoms and which risk factors are associated with their development remain unclear. Methods: The present systematic review aimed at giving a comprehensive overview of corticosteroids-induced symptoms of mania and/or psychosis and at examining the clinical factors that might increase the risk of developing these adverse reactions. According to PRISMA guidelines, this systematic review included 40 papers (clinical cases = 34; quantitative research = 6). Results: In 64.7% of clinical cases and 33.3% of research studies reviewed, patients taking corticosteroids presented with both manic and psychotic symptoms; in 11.8% of clinical cases and 1 (out of 6) quantitative research patients under corticosteroids presented with manic symptoms only, whereas in 23.5% of clinical cases and 3 quantitative studies, psychotic symptoms only. Prolonged and high-dose corticosteroid therapy, pre-existing psychiatric conditions, older age and female sex represent risk factors, which are likely to increase individual susceptibility to corticosteroid-induced symptoms of mania and/or psychosis. Discussion: Although manic and psychotic symptoms often coexist in patients taking corticosteroids, the direction and nature of this relationship (e.g., which symptoms appear first, their interaction and progression over time) remain unclear. Clinicians prescribing corticosteroids might take advantage of clinimetric methods, which may allow a substantial improvement in the early detection and evaluation of severity of corticosteroid-induced manic and/or psychotic symptoms

    Equilibrium and non-equilibrium studies on certain chemical systems I. Equilibrium thermochemical investigations on selected sugars and spiranes. II. Shear viscosity studies on [alpha]-olefins and normal alcohols

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    Precision oxygen-bomb calorimetry measurements have been conducted in three areas of investigation. The areas of investigation are: 1) the construction of a predictive standard enthalpy of formation correlation procedure for spriroalkane compounds and, specifically, the nature and contribution of the spiro-carbon atom; 2) the enthalpies of combustion and formation of aldopentoses; and 3) the enthalpies of combustion and formation of maltose and lactose sugars. Enthalpies of vaporization have been determined for selected spiroalkanes and the enthalpies of melting and desorption for the hydrated sugars have been determined by a dynamical method. High precision kinematic shear viscosities have been measured for certain normal alcohols and ��-olefins from -20��C to about 80��C. The experimental data are analyzed with respect to the Andrade equation, the Eyring density dependent equation, the Batschinski-Hildebrand equation, and a generalized empirical equation. In order to understand the energy-structural relations in the spiroalkanes, the enthalpies of combustion for spiro[4.5]decane, spiro[5.5]lundecane, spiro[5.6]dodecane, and 7-n-hexadecyl-spiro[4.5]decane were determined by static oxygen-bomb calorimetry. From these measurements, the spiro-carbon atom contribution to the strain energy of the spirane molecules has been ascertained. ..

    A randomized, Phase IIb study investigating oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (µ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty

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    Neil Singla,1 Harold S Minkowitz,2 David G Soergel,3 David A Burt,3 Ruth Ann Subach,3 Monica Y Salamea,3 Michael J Fossler,3 Franck Skobieranda3 1Lotus Clinical Research, Pasadena, CA, 2Memorial Hermann Memorial City Medical Center, Houston, TX, 3Trevena, Inc, King of Prussia, PA, USA Background: Oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (µ-GPS) modulator, was designed to improve the therapeutic window of conventional opioids by activating G-protein signaling while causing low β-arrestin recruitment to the µ receptor. This randomized, double-blind, patient-controlled analgesia Phase IIb study was conducted to investigate the efficacy, safety, and tolerability of oliceridine compared with morphine and placebo in patients with moderate to severe pain following abdominoplasty (NCT02335294; oliceridine is an investigational agent not yet approved by the US Food and Drug Administration). Methods: Patients were randomized to receive postoperative regimens of intravenous oliceridine (loading/patient-controlled demand doses [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B]), morphine (4.0/1.0), or placebo with treatment initiated within 4 hours of surgery and continued as needed for 24 hours. Results: Two hundred patients were treated (n=39, n=39, n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and placebo groups, respectively). Patients were predominantly female (n=198 [99%]) and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of 7.7 (on 11-point numeric pain rating scale). Patients receiving the oliceridine regimens had reductions in average pain scores (model-based change in time-weighted average versus placebo over 24 hours) of 2.3 and 2.1 points, respectively (P=0.0001 and P=0.0005 versus placebo); patients receiving morphine had a similar reduction (2.1 points; P<0.0001 versus placebo). A lower prevalence of adverse events (AEs) related to nausea, vomiting, and respiratory function was observed with the oliceridine regimens than with morphine (P<0.05). Other AEs with oliceridine were generally dose-related and similar in nature to those observed with conventional opioids; no serious AEs were reported with oliceridine. Conclusion: These results suggest that oliceridine may provide effective, rapid analgesia in patients with moderate to severe postoperative pain, with an acceptable safety/tolerability profile and potentially wider therapeutic window than morphine. Keywords: TRV130, acute pain, analgesic, opioid, biased ligan

    Psychopathological Burden among Healthcare Workers during the COVID-19 Pandemic Compared to the Pre-Pandemic Period

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    This retrospective observational study on hospital staff requesting an “application visit” (from 2017 to 2022) at the Occupational Medicine department aimed at comparing a “pre-COVID group” (2017–2019) with a “COVID group” (2020–2022) regarding (a) sociodemographic data (i.e., age, sex, occupation, years of employment at the hospital), (b) rate and type of psychiatric diagnoses in both groups and rate of psychiatric diagnoses per subject, and (c) rate of drug/psychotherapeutic prescriptions. Two hundred and five healthcare workers (F = 73.7%; mean age = 50.7 ± 10.33) were visited. Compared with the pre-COVID group, healthcare workers evaluated during COVID-19 were significantly younger and reported fewer years of employment at the hospital. Although rates of primary psychiatric diagnoses were similar in both samples, an increased number of psychopathologies per subject and associated treatment prescriptions in the COVID group was observed. In the COVID group, 61% had one psychiatric diagnosis, and 28% had 2+ psychiatric diagnoses, compared with 83.8% and 6.7% of pre-COVID. Furthermore, 56.2%/1.9% in pre-COVID and 73%/6% in the COVID group were prescribed drugs/psychotherapy, respectively. The findings of the present study highlighted an increase in both younger workers’ requests and psychiatric comorbidities during the pandemic, representing a burden on the Italian healthcare system. It is thus relevant to address the mental health challenges of healthcare workers accordingly

    Care manager role for older multimorbid heart failure patients’ needs in relation to psychological distress and quality of life: a cross-sectional study

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    Background There are few studies investigating patients’ needs in healthcare focusing on disease severity and psychological characteristics of elderly heart failure (HF) patients with multimorbidity, specifically addressed by a care manager (CM). Aims To explore the role of a CM dealing with elderly multimorbid HF patients’ needs/preferences according to NYHA class, ejection fraction, psychological/psychosomatic distress and quality of life (QoL), utilizing a Blended Collaborative Care (BCC) approach (ESCAPE; Grant agreement No 945377). Methods Cue cards, self-reported questionnaires, and a semi-structured interview were used to collect data. Results Twenty-five Italian patients (mean age ±  SD  = 77.5 ± 6.68) were enrolled between June 2021 and March 2022. The most relevant patients’ needs to be addressed by a CM were: education (e.g., on medical comorbidities), individual treatment tailoring (e.g., higher number of appointments with cardiologists) and symptom monitoring. Conclusion The study highlights the importance of targeting HF patients’ needs according to psychological characteristics, whose healthcare requires person-centered care with CM assistance. In view of ESCAPE BCC intervention, a CM should consider specific patients’ needs of elderly multimorbid HF patients with psychological, psychosomatic distress, particularly somatization, and lower QoL to achieve a more personalized health care pathway. Study registration The «Evaluation of a patient-centred biopsychosocial blended collaborative care pathway for the treatment of multi-morbid elderly patients» (ESCAPE) study has been registered at the University of Göttingen Medical Centre (UMG Reg. No 02853) and the German Clinical Trials Register (DRKS00025120)

    Teacher, administrator, and professional business partner perceptions of the effectiveness of the Oak Creek High School Advisory Board

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    Plan BAt the beginning of the 2017-2018 academic year, the Oak Creek-Franklin Joint School District implemented a Career and Technical Education Advisory Board comprised of teachers, administrators, and local business professionals. The mission of the board is to "provide business partners, community leaders, and teachers an opportunity to improve student learning outcomes and to expand CTE experiences for students." CTE advisory boards that follow best practices in CTE advisory board implementation and development engage members, create work-based learning opportunities for students, and create opportunities for CTE students by partnering events that allow students and community members to collaborate. Through this qualitative study, members of the Oak Creek CTE Advisory Board described the effectiveness of the board in regards to curriculum development, work-based learning opportunities, and the ability to create partnerships for events. Findings from the data defined the current effectiveness of the board and provided a blueprint for successful practices for the future. The results of the study demonstrated that teachers and administrators perceived the advisory board to be more effective than professional business member counterparts in the areas of curriculum development and the ability of the board to create events that featured student and community member collaboration

    A sensitive soma-localized red fluorescent calcium indicator for in vivo imaging of neuronal populations at single-cell resolution.

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    Recent advancements in genetically encoded calcium indicators, particularly those based on green fluorescent proteins, have optimized their performance for monitoring neuronal activities in a variety of model organisms. However, progress in developing red-shifted GECIs, despite their advantages over green indicators, has been slower, resulting in fewer options for end users. In this study, we explored topological inversion and soma-targeting strategies, which are complementary to conventional mutagenesis, to re-engineer a red genetically encoded calcium indicator, FRCaMP, for enhanced in vivo performance. The resulting sensors, FRCaMPi and soma-targeted FRCaMPi (SomaFRCaMPi), exhibit up to 2-fold higher dynamic range and peak ΔF/F0 per single AP compared to widely used jRGECO1a in neurons both in culture and in vivo. Compared to jRGECO1a and FRCaMPi, SomaFRCaMPi reduces erroneous correlation of neuronal activity in the brains of mice and zebrafish by two- to 4-fold due to diminished neuropil contamination without compromising the signal-to-noise ratio. Under wide-field imaging in primary somatosensory and visual cortices in mice with high labeling density (80-90%), SomaFRCaMPi exhibits up to 40% higher SNR and decreased artifactual correlation across neurons. Altogether, SomaFRCaMPi improves the accuracy and scale of neuronal activity imaging at single-neuron resolution in densely labeled brain tissues due to a 2-3-fold enhanced automated neuronal segmentation, 50% higher fraction of responsive cells, up to 2-fold higher SNR compared to jRGECO1a. Our findings highlight the potential of SomaFRCaMPi, comparable to the most sensitive soma-targeted GCaMP, for precise spatial recording of neuronal populations using popular imaging modalities in model organisms such as zebrafish and mice

    GAF-CaMP3–sfGFP, An Enhanced Version of the Near-Infrared Genetically Encoded Positive Phytochrome-Based Calcium Indicator for the Visualization of Neuronal Activity

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    The first generation of near-infrared, genetically encoded calcium indicators (NIR-GECIs) was developed from bacterial phytochrome-based fluorescent proteins that utilize biliverdin (BV) as the chromophore moiety. However, NIR-GECIs have some main drawbacks such as either an inverted response to calcium ions (in the case of NIR-GECO1) or a limited dynamic range and a lack of data about their application in neurons (in the case of GAF-CaMP2–superfolder green fluorescent protein (sfGFP)). Here, we developed an enhanced version of the GAF-CaMP2–sfGFP indicator, named GAF-CaMP3–sfGFP. The GAF-CaMP3–sfGFP demonstrated spectral characteristics, molecular brightness, and a calcium affinity similar to the respective characteristics for its progenitor, but a 2.9-fold larger DF/F response to calcium ions. As compared to GAF-CaMP2–sfGFP, in cultured HeLa cells, GAF-CaMP3–sfGFP had similar brightness but a 1.9-fold larger DF/F response to the elevation of calcium ions levels. Finally, we successfully utilized the GAF-CaMP3–sfGFP for the monitoring of the spontaneous and stimulated activity of neuronal cultures and compared its performance with the R-GECO1 indicator using two-color confocal imaging. In the cultured neurons, GAF-CaMP3–sfGFP showed a linear DF/F response in the range of 0–20 APs and in this range demonstrated a 1.4-fold larger DF/F response but a 1.3- and 2.4-fold slower rise and decay kinetics, respectively, as compared to the same parameters for the R-GECO1 indicator

    Conversion of red fluorescent protein into a bright blue probe

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    At the time of publication, David Grünwald was not yet affiliated with the University of Massachusetts Medical School.We used a red chromophore formation pathway, in which the anionic red chromophore is formed from the neutral blue intermediate, to suggest a rational design strategy to develop blue fluorescent proteins with a tyrosine-based chromophore. The strategy was applied to red fluorescent proteins of the different genetic backgrounds, such as TagRFP, mCherry, HcRed1, M355NA, and mKeima, which all were converted into blue probes. Further improvement of the blue variant of TagRFP by random mutagenesis resulted in an enhanced monomeric protein, mTagBFP, characterized by the substantially higher brightness, the faster chromophore maturation, and the higher pH stability than blue fluorescent proteins with a histidine in the chromophore. The detailed biochemical and photochemical analysis indicates that mTagBFP is the true monomeric protein tag for multicolor and lifetime imaging, as well as the outstanding donor for green fluorescent proteins in Forster resonance energy transfer applications
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