ABSTRACT
Capture of a photon by an opsin visual pigment isomerizes its 11-cis-retinaldehyde (11cRAL) chromophore to all-trans-retinaldehyde (atRAL), which subsequently dissociates. To restore light sensitivity, the unliganded apo-opsin combines with another 11cRAL to make a new visual pigment. Two enzyme pathways supply chromophore to photoreceptors. The canonical visual cycle in retinal pigment epithelial cells supplies 11cRAL at low rates. The photic visual cycle in Müller cells supplies cones with 11-cis-retinol (11cROL) chromophore precursor at high rates. Although rods can only use 11cRAL to regenerate rhodopsin, cones can use 11cRAL or 11cROL to regenerate cone visual pigments. We performed a screen in zebrafish retinas and identified ZCRDH as a candidate for the enzyme that converts 11cROL to 11cRAL in cone inner segments. Retinoid analysis of eyes from Zcrdh-mutant zebrafish showed reduced 11cRAL and increased 11cROL levels, suggesting impaired conversion of 11cROL to 11cRAL. By microspectrophotometry, isolated Zcrdh-mutant cones lost the capacity to regenerate visual pigments from 11cROL. ZCRDH therefore possesses all predicted properties of the cone 11cROL dehydrogenase. The human protein most similar to ZCRDH is RDH12. By immunocytochemistry, ZCRDH was abundantly present in cone inner segments, similar to the reported distribution of RDH12. Finally, RDH12 was the only mammalian candidate protein to exhibit 11cROL-oxidase catalytic activity. These observations suggest that RDH12 in mammals is the functional ortholog of ZCRDH, which allows cones, but not rods, to regenerate visual pigments from 11cROL provided by Müller cells. This capacity permits cones to escape competition from rods for visual chromophore in daylight-exposed retinas.
Subject(s)
Alcohol Oxidoreductases , Retinal Cone Photoreceptor Cells , Retinal Rod Photoreceptor Cells , Zebrafish , Animals , Zebrafish/physiology , Retinal Cone Photoreceptor Cells/metabolism , Retinal Cone Photoreceptor Cells/physiology , Retinal Rod Photoreceptor Cells/metabolism , Retinal Rod Photoreceptor Cells/physiology , Alcohol Oxidoreductases/metabolism , Alcohol Oxidoreductases/genetics , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Retinaldehyde/metabolism , Retinal Pigments/metabolism , Humans , Opsins/metabolism , Opsins/geneticsABSTRACT
Computational whole-brain models describe the resting activity of each brain region based on a local model, inter-regional functional interactions, and a structural connectome that specifies the strength of inter-regional connections. Strokes damage the healthy structural connectome that forms the backbone of these models and produce large alterations in inter-regional functional interactions. These interactions are typically measured by correlating the time series of the activity between two brain regions in a process, called resting functional connectivity. We show that adding information about the structural disconnections produced by a patient's lesion to a whole-brain model previously trained on structural and functional data from a large cohort of healthy subjects enables the prediction of the resting functional connectivity of the patient and fits the model directly to the patient's data (Pearson correlation = 0.37; mean square error = 0.005). Furthermore, the model dynamics reproduce functional connectivity-based measures that are typically abnormal in stroke patients and measures that specifically isolate these abnormalities. Therefore, although whole-brain models typically involve a large number of free parameters, the results show that, even after fixing those parameters, the model reproduces results from a population very different than that on which the model was trained. In addition to validating the model, these results show that the model mechanistically captures the relationships between the anatomical structure and the functional activity of the human brain.
ABSTRACT
Bone releases calcium and phosphate in response to pro-inflammatory cytokine-mediated inflammation. The body develops impaired urinary excretion of phosphate with age and chronic inflammation given the reduction of the kidney protein Klotho, which is essential to phosphate excretion. Phosphate may also play a role in the development of the resistance of the parathyroid calcium-sensing receptor (CaSR) to circulating calcium thus contributing to calcium retention in the circulation. Phosphate can contribute to vascular smooth muscle dedifferentiation with manifestation of osteoblastogenesis and ultimately endovascular calcium phosphate precipitation. Thus phosphate, along with calcium, contributes to the calcification and inflammation of atherosclerotic plaques and the origin of these elements is likely the bone, which serves as storage for the majority of the body's supply of extracellular calcium and phosphate. Early cardiac evaluation of patients with chronic inflammation and attempts at up-regulating the parathyroid CaSR with calcimimetics or introducing earlier anti-resorptive treatment with bone active pharmacologic agents may serve to delay onset or reduce the quantity of atherosclerotic plaque calcification in these patients.
Subject(s)
Calcium , Inflammation , Phosphates , Receptors, Calcium-Sensing , Vascular Calcification , Humans , Vascular Calcification/metabolism , Phosphates/metabolism , Calcium/metabolism , Inflammation/metabolism , Receptors, Calcium-Sensing/metabolism , Animals , Coronary Vessels/metabolismABSTRACT
This review examines our current understanding of consensus definitions for frailty, sarcopenia, and cachexia and their perceived overlap with malnutrition. Patients with these syndromes will often meet the criteria for malnutrition. It is common for these overlap syndromes to be misapplied by practitioners, and confusion has been further exacerbated by the lack of a common malnutrition language. To address the latter concern, we recommend using either the standalone Global Leadership Initiative in Malnutrition (GLIM) framework or the GLIM consensus criteria integrated with other accepted approaches as dictated by preference and available resources. Established care standards should guide the recognition and treatment of malnutrition to promote optimal clinical outcomes and quality of life. The effectiveness of nutrition interventions may be reduced in settings of severe acute inflammation and in end-stage disease that is associated with cachexia. However, such interventions may still assist patients to tolerate treatments that target the underlying etiology for an overlap syndrome, and they may help to improve select clinical outcomes and quality of life. Recent, large, well-designed randomized controlled trials have demonstrated the compelling positive clinical effects of medical nutrition therapy. The application of concurrent malnutrition risk screening and assessment is therefore a high priority. The necessity to deliver specific interventions that target the underlying mechanisms of these overlap syndromes and also diagnose and address malnutrition is paramount. It must be highlighted that securing beneficial outcomes for frailty, sarcopenia, and cachexia will also require nonnutrition interventions, like comprehensive care plans, pharmacologic agents, and prescribed exercise.
ABSTRACT
Several decades of theory suggest that pathological narcissism (PN) may limit psychotherapy success, but empirical evidence for such theories is limited and mixed. In addition, it has been proposed that individuals with high levels of PN may benefit more from supportive compared to interpretive psychodynamic therapies, but no studies thus far have investigated this question empirically. As such, our study aimed to extend past research by investigating (a) whether higher levels of pretreatment PN predict poorer treatment outcome and (b) whether the type of psychodynamic therapy (supportive or interpretive therapy) moderates these findings, in a sample of patients undergoing group psychodynamic psychotherapy for perfectionism. The sample was drawn from the University of British Columbia Perfectionism Treatment Study II (Hewitt et al., 2023) and consisted of 80 treatment-seeking adults with elevated perfectionism. Contrary to expectations, multilevel and multiple regression analyses showed that pretreatment PN did not significantly predict posttreatment changes in symptom severity, life satisfaction, or work and social impairment. We also did not find that either grandiose or vulnerable narcissism predicted likelihood of patient dropout. Finally, treatment type did not moderate the relationship between pretreatment PN and treatment outcome, suggesting that, contrary to our hypotheses, PN does not impact treatment outcome regardless of the interpretive nature of the psychodynamic group therapy. These results, taken together with past findings, suggest that PN may not be associated with poorer psychotherapy outcomes in certain contexts, such as in the case of supportive or interpretive psychodynamic group psychotherapy for perfectionism. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Subject(s)
Narcissism , Perfectionism , Psychotherapy, Group , Psychotherapy, Psychodynamic , Humans , Female , Male , Adult , Psychotherapy, Group/methods , Psychotherapy, Psychodynamic/methods , Treatment Outcome , Personality Disorders/therapy , Personality Disorders/psychology , Middle Aged , Young Adult , Narcissistic Personality DisorderABSTRACT
BACKGROUND: Phosphate buffer is often used as a replacement for the physiological bicarbonate buffer in pharmaceutical dissolution testing, although there are some discrepancies in their properties making it complicated to extrapolate dissolution results in phosphate to the in vivo situation. This study aims to characterize these discrepancies regarding solubility and dissolution behavior of ionizable compounds. METHODS: The dissolution of an ibuprofen powder with a known particle size distribution was simulated in silico and verified experimentally in vitro at two different doses and in two different buffers (5 mM pH 6.8 bicarbonate and phosphate). RESULTS: The results showed that there is a solubility vs. dissolution mismatch in the two buffers. This was accurately predicted by the in-house simulations based on the reversible non-equilibrium (RNE) and the Mooney models. CONCLUSIONS: The results can be explained by the existence of a relatively large gap between the initial surface pH of the drug and the bulk pH at saturation in bicarbonate but not in phosphate, which is caused by not all the interfacial reactions reaching equilibrium in bicarbonate prior to bulk saturation. This means that slurry pH measurements, while providing surface pH estimates for buffers like phosphate, are poor indicators of surface pH in the intestinal bicarbonate buffer. In addition, it showcases the importance of accounting for the H2CO3-CO2 interconversion kinetics to achieve good predictions of intestinal drug dissolution.
Subject(s)
Bicarbonates , Drug Liberation , Ibuprofen , Phosphates , Solubility , Buffers , Bicarbonates/chemistry , Hydrogen-Ion Concentration , Ibuprofen/chemistry , Phosphates/chemistry , Particle Size , Computer Simulation , Powders/chemistry , Kinetics , Chemistry, Pharmaceutical/methodsABSTRACT
BACKGROUND: Experiencing symptoms of traumatic stress may be the cost of caring for trauma patients. Emergency nurses caring for trauma patients are at risk for traumatic stress reactions. OBJECTIVE: This study explored the stress and coping behaviors experienced by emergency nurses who provide trauma care. METHODS: Focus groups were held at three urban trauma centers in the Midwestern United States: a Level I pediatric trauma center, a Level I adult trauma center, and a Level III adult trauma center. Data were collected between December 2009 and March 2010. Data analysis was guided by the principles of grounded theory. Line-by-line coding and constant comparative analysis techniques were used to identify recurring constructs. RESULTS: A total of 48 emergency nurses participated. Recurring constructs emerged in the data analysis and coding, revealing four major themes: care of the trauma patient, professional practice, personal life, and support. CONCLUSIONS: Nurse job engagement, burnout, and professional and personal relationships are influenced by trauma patient care. The study's resulting themes of care of the trauma patient, professional practice, personal life, and support resulted in the development of the "trauma nursing is a continual experience theory" that can be used as a framework to address these effects. Intentional support and timely interventions based on this new theory can help mitigate the effects of traumatic stress experienced by trauma nurses.
Subject(s)
Adaptation, Psychological , Emergency Nursing , Focus Groups , Grounded Theory , Nursing Staff, Hospital , Qualitative Research , Trauma Centers , Humans , Female , Adult , Male , Middle Aged , Midwestern United States , Nursing Staff, Hospital/psychology , Trauma Nursing , Burnout, Professional/psychology , Wounds and Injuries/nursing , Wounds and Injuries/psychologyABSTRACT
Mitochondrial dynamics were examined in human dermal fibroblasts biopsied from a confirmed Leber's Hereditary Optic Neuropathy (LHON) patient with a homoplasmic G11778A mutation of the mitochondrial genome. Expression of the G11778A mutation did not impart any discernible difference in mitochondrial network morphology using widefield fluorescence microscopy. However, at the ultrastructural level, cells expressing this mutation exhibited an impairment of mitochondrial morphological plasticity when forced to utilize oxidative phosphorylation (OXPHOS) by transition to glucose-free, galactose-containing media. LHON fibroblasts also displayed a transient increase in mitophagy upon transition to galactose media. These results provide new insights into the consequences of the G11778A mutation of LHON and the pathological mechanisms underlying this disease.
Subject(s)
Fibroblasts , Mitochondria , Mitophagy , Mutation , Optic Atrophy, Hereditary, Leber , Humans , Mitophagy/genetics , Optic Atrophy, Hereditary, Leber/genetics , Optic Atrophy, Hereditary, Leber/pathology , Optic Atrophy, Hereditary, Leber/metabolism , Mitochondria/metabolism , Mitochondria/genetics , Mitochondria/pathology , Fibroblasts/metabolism , Fibroblasts/pathology , Oxidative Phosphorylation , Cells, CulturedABSTRACT
Leber's hereditary optic neuropathy (LHON) is a visual impairment associated with mutations of mitochondrial genes encoding elements of the electron transport chain. While much is known about the genetics of LHON, the cellular pathophysiology leading to retinal ganglion cell degeneration and subsequent vision loss is poorly understood. The impacts of the G11778A mutation of LHON on bioenergetics, redox balance and cell proliferation were examined in patient-derived fibroblasts. Replacement of glucose with galactose in the culture media reveals a deficit in the proliferation of G11778A fibroblasts, imparts a reduction in ATP biosynthesis, and a reduction in capacity to accommodate exogenous oxidative stress. While steady-state ROS levels were unaffected by the LHON mutation, cell survival was diminished in response to exogenous H2O2.
Subject(s)
DNA, Mitochondrial , Fibroblasts , Galactose , Mutation , Optic Atrophy, Hereditary, Leber , Humans , Fibroblasts/metabolism , Fibroblasts/drug effects , Optic Atrophy, Hereditary, Leber/genetics , Optic Atrophy, Hereditary, Leber/metabolism , Optic Atrophy, Hereditary, Leber/pathology , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Galactose/metabolism , Mutation/genetics , Cell Proliferation/drug effects , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/genetics , Cells, Cultured , Glucose/metabolism , Glucose/pharmacologyABSTRACT
Though rod and cone photoreceptors use similar phototransduction mechanisms, previous model calculations have indicated that the most important differences in their light responses are likely to be differences in amplification of the G-protein cascade, different decay rates of phosphodiesterase (PDE) and pigment phosphorylation, and different rates of turnover of cGMP in darkness. To test this hypothesis, we constructed TrUx;GapOx rods by crossing mice with decreased transduction gain from decreased transducin expression, with mice displaying an increased rate of PDE decay from increased expression of GTPase-activating proteins (GAPs). These two manipulations brought the sensitivity of TrUx;GapOx rods to within a factor of 2 of WT cone sensitivity, after correcting for outer-segment dimensions. These alterations did not, however, change photoreceptor adaptation: rods continued to show increment saturation though at a higher background intensity. These experiments confirm model calculations that rod responses can mimic some (though not all) of the features of cone responses after only a few changes in the properties of transduction proteins.
Subject(s)
Retinal Cone Photoreceptor Cells , Retinal Rod Photoreceptor Cells , Transducin , Animals , Retinal Cone Photoreceptor Cells/metabolism , Retinal Rod Photoreceptor Cells/metabolism , Mice , Transducin/metabolism , Transducin/genetics , Retina/metabolism , Phosphoric Diester Hydrolases/metabolism , Phosphoric Diester Hydrolases/geneticsABSTRACT
INTRODUCTION: Recent insights regarding mechanisms mediating stemness, heterogeneity, and metastatic potential of lung cancers have yet to be fully translated to effective regimens for the treatment of these malignancies. This study sought to identify novel targets for lung cancer therapy. METHODS: Transcriptomes and DNA methylomes of 14 SCLC and 10 NSCLC lines were compared with normal human small airway epithelial cells (SAECs) and induced pluripotent stem cell (iPSC) clones derived from SAEC. SCLC lines, lung iPSC (Lu-iPSC), and SAEC were further evaluated by DNase I hypersensitive site sequencing (DHS-seq). Changes in chromatin accessibility and depths of transcription factor (TF) footprints were quantified using Bivariate analysis of Genomic Footprint. Standard techniques were used to evaluate growth, tumorigenicity, and changes in transcriptomes and glucose metabolism of SCLC cells after NFIC knockdown and to evaluate NFIC expression in SCLC cells after exposure to BET inhibitors. RESULTS: Considerable commonality of transcriptomes and DNA methylomes was observed between Lu-iPSC and SCLC; however, this analysis was uninformative regarding pathways unique to lung cancer. Linking results of DHS-seq to RNA sequencing enabled identification of networks not previously associated with SCLC. When combined with footprint depth, NFIC, a transcription factor not previously associated with SCLC, had the highest score of occupancy at open chromatin sites. Knockdown of NFIC impaired glucose metabolism, decreased stemness, and inhibited growth of SCLC cells in vitro and in vivo. ChIP-seq analysis identified numerous sites occupied by BRD4 in the NFIC promoter region. Knockdown of BRD4 or treatment with Bromodomain and extra-terminal domain (BET) inhibitors (BETis) markedly reduced NFIC expression in SCLC cells and SCLC PDX models. Approximately 8% of genes down-regulated by BETi treatment were repressed by NFIC knockdown in SCLC, whereas 34% of genes repressed after NFIC knockdown were also down-regulated in SCLC cells after BETi treatment. CONCLUSIONS: NFIC is a key TF and possible mediator of transcriptional regulation by BET family proteins in SCLC. Our findings highlight the potential of genome-wide chromatin accessibility analysis for elucidating mechanisms of pulmonary carcinogenesis and identifying novel targets for lung cancer therapy.
Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Mice , Animals , Small Cell Lung Carcinoma/genetics , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/metabolism , NFI Transcription Factors/genetics , NFI Transcription Factors/metabolism , Genome-Wide Association Study , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Decades of research implicate perfectionism as a risk factor for psychopathology. Most research has focused on trait perfectionism (i.e., needing to be perfect), but there is a growing focus on perfectionistic self-presentation (PSP) (i.e., the need to seem perfect). The current article reports the results of a meta-analysis of previous research on the facets of PSP and psychopathology outcomes (either clinical diagnoses of psychiatric disorders or symptoms of these disorders). A systematic literature search retrieved 30 relevant studies (37 samples; N = 15,072), resulting in 192 individual effect-size indexes that were analysed with random-effect meta-analysis. Findings support the notion of PSP as a transdiagnostic factor by showing that PSP facets are associated with various forms of psychopathology, especially social anxiety, depression, vulnerable narcissism and-to lesser extent-grandiose narcissism and anorexia nervosa. The results indicated that there both commonalities across the three PSP and some unique findings highlighting the need to distinguish among appearing perfect, avoiding seeming imperfect and avoiding disclosures of imperfections. Additional analyses yielded little evidence in the results across studies including undergraduates, community samples and clinical samples. Our discussion includes a focus on factors and processes that contribute to the association between PSP and psychopathology.
Subject(s)
Perfectionism , Humans , Mood Disorders , Narcissism , PsychopathologyABSTRACT
The objectives of this study were to determine the effect of COVID-19 on physical therapy (PT) mobilization of trauma patients and to determine if mobilization affected patient course in the ICU. This retrospective study included patients who were admitted to the ICU of a level II trauma center. The patients were divided into two groups, i.e., those admitted before (n = 378) and after (n = 499) 1 April 2020 when Georgia's COVID-19 shelter-in-place order was mandated. The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. A secondary analysis focused specifically on the after-COVID patients examined the extent to which mobilization (n = 328) or lack of mobilization (n = 171) influenced ICU outcomes (e.g., mortality, readmission). The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. The after-COVID patients had higher injury severity as a greater proportion was classified as severely injured (i.e., >15 on Injury Severity Score) compared to the before-COVID patients. After-COVID patients also had a greater cumulative number of comorbidities and experienced greater complications in the ICU. Despite this, there was no difference between patients in receiving a PT consultation or days to mobilization. Within the after-COVID cohort, those who were mobilized were older, had greater Glasgow Coma Scale scores, had longer total hospital days, and had a lesser mortality rate, and a higher proportion were female. Despite shifting patient injury attributes post-COVID-19, a communicable disease, mobilization care remained consistent and effective.
ABSTRACT
The dissolution testing method described in the United States Pharmacopeia (USP) Chapter ⟨711⟩ is widely used for assessing the release of active pharmaceutical ingredients from solid dosage forms. However, extensive use over the years has revealed certain issues, including high experimental intervariability observed in specific formulations and the settling of particles in the dead zone of the vessel. To address these concerns and gain a comprehensive understanding of the hydrodynamic conditions within the USP 2 apparatus, computational fluid dynamic simulations have been employed in this study. The base design employed in this study is the 900 mL USP 2 vessel along with a paddle stirrer at a 50 rpm rotational speed. Additionally, alternative stirrer designs, including the hydrofoil, pitched blade, and Rushton impeller, are investigated. A comparison is also made between a flat-bottom tank and the USP round-bottom vessel of the same volume and diameter. Furthermore, this work examines the impact of various parameters, such as clearance distance (distance between the bottom of the impeller and bottom of the vessel), number of impeller blades, impeller diameter, and impeller attachment angle. The volume-average shear rate (Stv), fluid velocity (Utv), and energy dissipation rates (ϵtv) represent the key properties evaluated in this study. Comparing the USP2 design and systems with the same stirrer but flat-bottom vessel reveals more homogeneous mixing compared to the USP2 design. Analyzing fluid flow streamlines in different designs demonstrates that hydrofoil stirrers generate more suspension or upward movement of fluid compared to paddle stirrers. Therefore, when impellers are of a similar size, hydrofoil designs generate higher fluid velocities in the coning area. Furthermore, the angle of blade attachment to the hub influences the fluid velocity in the coning area in a way that the 60° angle design generates more suspension than the 45° angle design. The findings indicate that the paddle stirrer design leads to a heterogeneous shear rate and velocity distributions within the vessel compared with the other designs, suggesting suboptimal performance. These insights provide valuable guidance for the development of improved in vitro dissolution testing devices, emphasizing the importance of optimized design considerations to minimize hydrodynamic variability, enhance dissolution characterization, and reduce variability in dissolution test results. Ultimately, such advancements hold potential for improving in vitro-in vivo correlations in drug development.
Subject(s)
Hydrodynamics , Solubility , Drug Liberation , Chemistry, Pharmaceutical/methods , Pharmacopoeias as Topic , Computer Simulation , Equipment Design , Drug Compounding/methods , United StatesABSTRACT
BACKGROUND: The United States makes up 4.4% of the world's population but nearly a quarter of the world's incarcerated population. Despite caring for nearly 2 million incarcerated persons and managing their unique needs, little is known about how this work spills over and affects the nurses who work in correctional settings. STUDY OBJECTIVE: This descriptive study aimed to (a) examine write-in answers regarding correctional nurse perceptions of how their work impacts their health and their home lives and (b) explore correctional nurse responses for how to improve the work environment to better support their well-being. METHOD: The researchers compiled and analyzed qualitative data from a cross-sectional study where U.S. correctional nurses (N = 270) completed an online survey. Manifest content analysis was used to analyze optional write-in data. RESULTS: Approximately 41% (n = 111) of participants answered qualitative questions. Participants were primarily White (77.3%) and non-Hispanic or Latino (88.7%), working in prisons (65.8%), and employed by the state (63.8%) as registered nurses (70%). Three major themes emerged: (a) "personal impact": increased stress and burnout, overwhelming work hours, and emotional and physical effects; (b) "social relationships and family impacts": withdrawn, strained homelife, and uncertainty; and (c) "need for change": improved staffing, reduced mandatory overtime, and better support from management. CONCLUSIONS: Correctional organizations may consider ways to support the well-being of their nurses through adequate staffing, flexible scheduling, decreased mandatory overtime, and hiring effective nurse managers as key members of the correctional team.
ABSTRACT
Introduction: The current article introduces the Loneliness Automatic Thoughts Questionnaire (LATQ) and describes research evaluating its psychometric properties and correlates. Methods: Two separate samples of university student participants (Study 1; N = 282, Study 2; N = 289) were administered the LATQ along with a battery of other measures. Whereas Study 1 involved a preliminary investigation of the psychometric properties of the LATQ, Study 2 provided an opportunity to further expand on this aim by assessing the concurrent validity of the measure across studies. Results: Overall, psychometric analyses confirmed that the LATQ items are measured with an adequate degree of internal consistency and confirmatory factor analyses established that the nine items loaded significantly on one replicable factor. Concurrent validity was established in terms of links with other loneliness measures and a measure of persistent and intrusive negative thoughts. Furthermore, LATQ scores were associated with anti-mattering, social hopelessness, anxiety, depression, and unbearable psychache. Moreover, regression analyses established that the LATQ predicted significant unique variance in depression and psychache beyond the variance attributable to measures of loneliness and adaptability to loneliness. Discussion: Collectively, results indicate that loneliness-related automatic thoughts represent a unique and important element of the loneliness construct. Future research applications and additional psychometric issues to address in future research are discussed and a need for a greater focus on the cognitive aspects of loneliness is explored.
ABSTRACT
Progesterone receptor (PR)-interacting compounds in the environment are associated with serious health hazards. However, methods for their detection in environmental samples are cumbersome. We report a sensitive activity-based biosensor for rapid and reliable screening of progesterone receptor (PR)-interacting endocrine disrupting chemicals (EDCs). The biosensor is a cell line which expresses nuclear mCherry-NF1 and a green fluorescent protein (GFP)-tagged chimera of glucocorticoid receptor (GR) N terminus fused to the ligand binding domain (LBD) of PR (GFP-GR-PR). As this LBD is shared by the PRA and PRB, the biosensor reports on the activation of both PR isoforms. This GFP-GR-PR chimera is cytoplasmic in the absence of hormone and translocates rapidly to the nucleus in response to PR agonists or antagonists in concentration- and time-dependent manner. In live cells, presence of nuclear NF1 label eliminates cell fixation and nuclear staining resulting in efficient screening. The assay can be used in screens for novel PR ligands and PR-interacting contaminants in environmental samples. A limited screen of river water samples indicated a widespread, low-level contamination with PR-interacting contaminants in all tested samples.
Subject(s)
Endocrine Disruptors , Receptors, Progesterone/genetics , Biological Assay , Cell Line , Cytoplasm , Green Fluorescent Proteins/genetics , Receptors, Glucocorticoid/geneticsABSTRACT
Objective: This randomized controlled trial investigated the efficacy of dynamic relational group therapy (DRT) relative to group psychodynamic supportive therapy (PST) in improving perfectionism-related attitudes and components of the perfectionistic self-relationship. Method: Based on a comprehensive conceptualization of perfectionism, 80 community-recruited, highly perfectionistic individuals were randomly allocated to 12 sessions of group DRT (n = 41; 5 groups) or group PST (n = 39; 5 groups). Patients completed measures of dysfunctional attitudes, self-criticism, self-esteem, and self-reassurance at pre-, mid-, and post-treatment, and six months post-treatment. Results: Multigroup latent growth curve modeling revealed significant (p < .05) decreases in dysfunctional attitudes, concern over mistakes, two types of self-criticism, and self-esteem problems, along with a significant increase in self-reassurance, from pre-treatment to six-month follow-up in both DRT and PST. Moderate-to-large between-group differences favoring DRT over PST were found for dysfunctional attitudes and self-reassurance. A majority of patients in both conditions maintained reliable improvement at six-month follow-up in dysfunctional attitudes, concern over mistakes, and self-criticism focused on inadequacy. Conclusion: Findings provide evidence for the use of psychodynamic group therapy approaches in treating perfectionism-related attitudes and self-relational elements of perfectionism, and support the relative efficacy of DRT for dysfunctional attitudes and self-reassurance.