1,357 research outputs found
The Relationship Between Service Utilization and Psychiatric Hospitalization Among People Diagnosed with Borderline Personality Disorder
This exploratory study was conducted to determine the relationship between service utilization and the psychiatric hospitalization among people diagnosed with borderline personality disorder (BPD). Secondary analysis was performed on the case files of 12 female adult clients of a rural county social service mental health department who are diagnosed with BPD. Results indicate that service utilization by this population is comparable regardless of time spent in acute psychiatric hospitals. Results further indicate that history of childhood sexual abuse was a predictor of hospitalization in this sample. A replication of this study which utilizes multiple methods is recommended. Implications for direct social work practice and policy are described
Bone Proteomics Method Optimization for Forensic Investigations
\ua9 2024 The Authors. Published by American Chemical Society.The application of proteomic analysis to forensic skeletal remains has gained significant interest in improving biological and chronological estimations in medico-legal investigations. To enhance the applicability of these analyses to forensic casework, it is crucial to maximize throughput and proteome recovery while minimizing interoperator variability and laboratory-induced post-translational protein modifications (PTMs). This work compared different workflows for extracting, purifying, and analyzing bone proteins using liquid chromatography with tandem mass spectrometry (LC-MS)/MS including an in-StageTip protocol previously optimized for forensic applications and two protocols using novel suspension-trap technology (S-Trap) and different lysis solutions. This study also compared data-dependent acquisition (DDA) with data-independent acquisition (DIA). By testing all of the workflows on 30 human cortical tibiae samples, S-Trap workflows resulted in increased proteome recovery with both lysis solutions tested and in decreased levels of induced deamidations, and the DIA mode resulted in greater sensitivity and window of identification for the identification of lower-abundance proteins, especially when open-source software was utilized for data processing in both modes. The newly developed S-Trap protocol is, therefore, suitable for forensic bone proteomic workflows and, particularly when paired with DIA mode, can offer improved proteomic outcomes and increased reproducibility, showcasing its potential in forensic proteomics and contributing to achieving standardization in bone proteomic analyses for forensic applications
Synonymous codons direct cotranslational folding toward different protein conformations.
In all genomes, most amino acids are encoded by more than one codon. Synonymous codons can modulate protein production and folding, but the mechanism connecting codon usage to protein homeostasis is not known. Here we show that synonymous codon variants in the gene encoding gamma-B crystallin, a mammalian eye-lens protein, modulate the rates of translation and cotranslational folding of protein domains monitored in real time by Forster resonance energy transfer and fluorescence-intensity changes. Gamma-B crystallins produced from mRNAs with changed codon bias have the same amino acid sequence but attain different conformations, as indicated by altered invivo stability and invitro protease resistance. 2D NMR spectroscopic data suggest that structural differences are associated with different cysteine oxidation states of the purified proteins, providing a link between translation, folding, and the structures of isolated proteins. Thus, synonymous codons provide a secondary code for protein folding in the cell
The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patients
\ua9 2024 The Author(s)Background: Medulloblastoma patients with a sub-total surgical resection (STR; >1.5 cm2 primary tumour residuum post-surgery) typically receive intensified treatment. However, the association of STR with poor outcomes has not been observed consistently, questioning the validity of STR as a high-risk disease feature. Methods: We collected extent of resection (EOR) data from 1110 patients (from UK CCLG centres (n = 416, collected between September 1990 and July 2014) and published (n = 694) cohorts), the largest cohort of molecularly and clinically annotated tumours assembled to specifically assess the significance of EOR. We performed association and univariable/multivariable survival analyses, assessing overall survival (OS) cohort-wide and with reference to the four consensus medulloblastoma molecular groups and clinical features. Findings: STR was reported in 20% (226/1110) of patients. Non-WNT (p = 0.047), children <5 years at diagnosis (p = 0.021) and metastatic patients (p < 0.0001) were significantly more likely to have a STR. In cohort-wide analysis, STR was associated with worse survival in univariable analysis (p < 0.0001). Examination of specific disease contexts showed that STR was prognostic in univariate analysis for patients receiving cranio-spinal irradiation (CSI) and chemotherapy (p = 0.016) and for patients with Group 3 tumours receiving CSI (p = 0.039). STR was not independently prognostic in multivariable analyses; outcomes for patients who have STR as their only risk-feature are as per standard-risk disease. Specifically, STR was not prognostic in non-metastatic patients that received upfront CSI. Interpretation: In a cohort of 1100 molecularly characterised medulloblastoma patients, STR (n = 226) predicted significantly lower OS in univariable analysis, but was not an independent prognostic factor. Our data suggest that maximal safe resection can continue to be carried out for patients with medulloblastoma and suggest STR should not inform patient management when observed as a sole, isolated risk-feature. Funding: Cancer Research UK, Newcastle Hospitals Charity, Children\u27s Cancer North, British Division of the International Academy of Pathology
Moral reasoning and homosexuality: the acceptability of arguments about lesbian and gay issues
In the political arena, lesbian and gay issues have typically been contested on grounds of human rights, but with variable success. Using a moral developmental framework, the purpose of this study was to explore preferences for different types of moral arguments when thinking about moral dilemmas around lesbian and gay issues. The analysis presented here comprised data collected from 545 students at UK universities, who completed a questionnaire, part of which comprised a moral dilemma task. Findings of the study showed that respondents do not apply moral reasoning consistently, and do not (clearly) favour human rights reasoning when thinking about lesbian and gay issues. Respondents tended to favour reasoning supporting existing social structures and frameworks, therefore this study highlights the importance of structural change in effecting widespread attitude change in relation to lesbian and gay rights issues. The implications of the findings for moral education are also discussed.</p
Child mental health in Jordanian orphanages: effect of placement change on behavior and caregiving
Background: To assess the mental health and behavioral problems of children in institutional placements in Jordan to inform understanding of current needs, and to explore the effects of placement change on functioning and staff
perceptions of goodness-of-fit.
Methods: An assessment was completed of 134 children between 1.5? 12 years-of-age residing in Jordanian orphanages. The Child Behavior Checklist was used to assess prevalence rates of problems across externalizing and internalizing behavior and DSM-IV oriented subscales. Also included was caregiver perceived goodness-of-fit with each child, caregiving behavior, and two placement change-clock variables; an adjustment clock measuring time since last move, and an anticipation clock measuring time to next move.
Results: 28% were in the clinical range for the internalizing domain on the CBCL, and 22% for the externalizing domain. The children also exhibited high levels of clinical range social problems, affective disorder, pervasive developmental disorder, and conduct problems. Internalizing problems were found to decrease with time in placement as children adjust to a prior move, whereas externalizing problems increased as the time to their next age-triggered move drew closer, highlighting the anticipatory effects of change. Both behavioral problems and the
change clocks were predictive of staff perceptions of goodness-of-fit with the children under their care.
Conclusions: These findings add to the evidence demonstrating the negative effects of orphanage rearing, and highlight the importance of the association between behavioral problems and child-caregiver relationship pathways including the timing of placement disruptions and staff perceptions of goodness-of-fit
Phylogeny and expression analysis of C-reactive protein (CRP) and serum amyloid-P (SAP) like genes reveal two distinct groups in fish
This work was funded by British Society of Animal Science/Genesis Faraday to both SAM and SB Immune control of energy reallocation in fish and a BBSRC Research Experience Placements (2010).Peer reviewedPublisher PD
Evaluation of analogues of furan-amidines as inhibitors of NQO2
Inhibitors of the enzyme NQO2 (NRH: quinone oxidoreductase 2) are of potential use in cancer chemotherapy and malaria. We have previously reported that non-symmetrical furan amidines are potent inhibitors of NQO2 and here novel analogues are evaluated. The furan ring has been changed to other heterocycles (imidazole, N-methylimidazole, oxazole, thiophene) and the amidine group has been replaced with imidate, reversed amidine, N-arylamide and amidoxime to probe NQO2 activity, improve solubility and decrease basicity of the lead furan amidine. All compounds were fully characterised spectroscopically and the structure of the unexpected product N-hydroxy-4-(5-methyl-4-phenylfuran-2-yl)benzamidine was established by X-ray crystallography. The analogues were evaluated for inhibition of NQO2, which showed lower activity than the lead furan amidine. The observed structure-activity relationship for the furan-amidine series with NQO2 was rationalized by preliminary molecular docking and binding mode analysis. In addition, the oxazole-amidine analogue inhibited the growth of Plasmodium falciparum with an IC50 value of 0.3 μM
Upper Limits on Gravitational Waves from Scorpius X-1 from a Model-Based Cross-Correlation Search in Advanced LIGO Data
We present the results of a semicoherent search for continuous gravitational waves from the low-mass X-ray binary Scorpius X-1, using data from the first Advanced LIGO observing run. The search method uses details of the modeled, parametrized continuous signal to combine coherently data separated by less than a specified coherence time, which can be adjusted to trade off sensitivity against computational cost. A search was conducted over the frequency range 25–, spanning the current observationally constrained range of binary orbital parameters. No significant detection candidates were found, and frequency-dependent upper limits were set using a combination of sensitivity estimates and simulated signal injections. The most stringent upper limit was set at , with comparable limits set across the most sensitive frequency range from 100 to . At this frequency, the 95% upper limit on the signal amplitude h 0 is marginalized over the unknown inclination angle of the neutron star\u27s spin, and assuming the best orientation (which results in circularly polarized gravitational waves). These limits are a factor of 3–4 stronger than those set by other analyses of the same data, and a factor of ~7 stronger than the best upper limits set using data from Initial LIGO science runs. In the vicinity of , the limits are a factor of between 1.2 and 3.5 above the predictions of the torque balance model, depending on the inclination angle; if the most likely inclination angle of 44° is assumed, they are within a factor of 1.7
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