• Harrison Vangsgaard opublikował 1 rok, 8 miesięcy temu

    Under such conditions, the functionalized Janus particles eventually achieved a limit of detection of 1 pg/mL. The rotational diffusometry realized by Janus particles was power-free and feasible for ultrasensitive detection, such as early disease detection.While thermal proteome profiling (TPP) shines in the field of drug target screening by analyzing the soluble fraction of the proteome samples treated at high temperature, the counterpart, the insoluble precipitate, has been overlooked for a long time. The analysis of the precipitate is hampered by the inefficient sample processing procedure. Herein, we propose a novel method, termed microparticle-assisted precipitation screening (MAPS), for drug target identification. The MAPS method exploits the principle that drug-bound proteins will be more resistant to thermal unfolding similar to the classic TPP method, but the process of protein precipitation is assisted by microparticles. Upon heating, proteins unfold and aggregate on the surface of the microparticles. The introduction of a microparticle simplifies the whole sample preparation workflow. The proteins that precipitate on the microparticles are subjected to washing, alkylation, and digestion. The whole sample preparation is processed conveniently on the surface of the microparticles without any transfer. With the assistance of microparticles, sample loss is minimized. The MAPS method is compatible with minute amounts of initial proteins. MAPS was applied to screen the targets of several well-studied drugs and the known target proteins were successfully identified with high confidence and specificity. To investigate the specificity of the method, MAPS was applied to screen the targets of the pan-kinase inhibitor, staurosporine, and 32 protein kinases (specificity of 80%) were identified using only 20 μg of initial proteins of each sample. MAPS is an unbiased robust method for drug target screening, filling the vacancy of stability-based target screening using a precipitate.

    We investigated whether the addition of Alzheimer’s disease-signature region cortical thickness (AD-Ct) and hippocampal volume (Hv) obtained from brain MRI to subjective memory complaints and informant-reports of cognitive decline enhances the screening accuracy for cognitive disorders in a memory clinic setting.

    120 participants (40 cognitively normal, 40 MCI, 40 dementia) underwent clinical evaluation, neuropsychological assessment, and brain MRI. The Subjective Memory Complaints Questionnaire (SMCQ) and Seoul Informant-Report Questionnaire for Dementia (SIRQD) were applied to assess subjective memory complaints and informant-reports of cognitive decline respectively. Logistic regression and ROC curve analyses were conducted to compare the screening abilities of SMCQ+SIRQD, SMCQ+SIRQD+Hv, and SMCQ+SIRQD+AD-Ct models for cognitive disorders.

    SMCQ+SIRQD+Hv model indicated better screening accuracy for MCI and overall cognitive disorder (CDall) than SMCQ+ SIRQD model. SMCQ+SIRQD+AD-Ct model had superior screening accuracy for dementia in comparison to SMCQ+SIRQD model. ROC curve analyses revealed that SMCQ+SIRQD+Hv model had the greatest area under the curve (AUC) for screening MCI and CDall (AUC 0.941 and 0.957), while SMCQ+SIRQD+AD-Ct model had the greatest AUC for screening dementia (AUC 0.966).

    Our results suggest that the addition of regional quantitative MRI data enhances the screening ability of subjective memory complaints and informant-reports of cognitive decline for MCI and dementia.

    Our results suggest that the addition of regional quantitative MRI data enhances the screening ability of subjective memory complaints and informant-reports of cognitive decline for MCI and dementia.

    Attentional biases toward emotional scenes may represent vulnerability and maintenance factors in depression. Antidepressant therapy may improve cognitive function and reduce depression, and is considered as the mechanism of action of antidepressants. Therefore, we conducted an eye-tracking test to examine whether selective serotonin re-uptake inhibitor (SSRI) antidepressants can reduce negative attentional biases and elicit clinical responses in depression.

    Twenty first-episode depressive patients freely viewed three types of pictures that depicted different emotional scenes (i.e., positive-control, neutral-control, and negative-control) for 4,000 ms while their eye movements were monitored. The attentional bias to different emotional scenes was assessed before and after eight weeks of SSRI treatment using the eye-tracking method. The control group included a group of healthy individuals.

    The results revealed that first-episode depressive patients oriented their gaze more frequently to negative images and less to happy images, compared to controls. Importantly, the attentional bias in depressive patients was regulated after eight weeks of SSRI treatment. Patients showed an increased tendency to fixate on positive images and a decreased tendency to focus on negative images.

    This suggests that SSRI antidepressants decrease vulnerability to negative images, while having an effect on attention in respect to positive images.

    This suggests that SSRI antidepressants decrease vulnerability to negative images, while having an effect on attention in respect to positive images.

    In 2011, „Suicide CARE” (Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea) was originally developed for the early detection of warning signs of suicide completion, since there is a tendency to regard emotional suppression as a virtue of Korean traditional culture. A total of 1.2 million individuals completed the training program of „Suicide CARE” in Korea.

    More sophisticated suicide prevention approaches according to age, sex, and occupation have been proposed, demanding for a more detailed revision of „Suicide CARE.” Thus, during the period from August 2019 to February 2020, „Suicide CARE” has been updated to version 2.0. The assessments on domestic gatekeeper training programs for suicide prevention, international gatekeeper training programs for suicide prevention, psychological autopsy interview reports between 2015 and 2018, and the evaluation of feedback from people who completed „Suicide CARE” version 1.6 training were performed.

    We describe the revision process of „Suicide CARE,” revealing that „Suicide CARE” version 2.0 has been developed using an evidence-based methodology.

    It is expected that „Suicide CARE” version 2.0 be positioned as the basic framework for many developing gatekeeper training programs for suicide prevention in Korea in the near future.

    It is expected that „Suicide CARE” version 2.0 be positioned as the basic framework for many developing gatekeeper training programs for suicide prevention in Korea in the near future.

    Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (SHC3) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of SHC3 and schizophrenia.

    An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population.

    The allelic and genotypic association analyses showed that four SNPs in SHC3 significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia.

    Our present results suggest SHC3 as a susceptibility gene for schizophrenia.

    Our present results suggest SHC3 as a susceptibility gene for schizophrenia.

    This study aimed to investigate the morphometric differences in the corpus callosum between patients with major depressive disorder (MDD) and healthy controls and analyze their relationship to gray matter changes.

    Twenty female MDD patients and 21 healthy controls (HCs) were included in the study. To identify the difference in the regional gray matter concentration (GMC), VBM was performed with T1 magnetic resonance imaging. The shape analysis of the corpus callosum was processed. Diffusion tensor imaging (DTI) fiber-tracking was performed to identify the regional tract pathways in the damaged corpus callosal areas.

    In the shape analysis, regional shape contractions in the rostrum and splenium were found in the MDD patients. VBM analysis showed a significantly lower white matter concentration in the genu and splenium, and a significantly lower GMC in the frontal, limbic, insular, and temporal regions of the MDD patients compared to the HCs. In DTI fiber-tracking, the fibers crossing the damaged areas of the genu, rostrum, and splenium were anatomically connected to the areas of lower GMC in MDD patients.

    These findings support that major depressive disorder may be due to disturbances in multiple neuronal circuits, especially those associated with the corpus callosum.

    These findings support that major depressive disorder may be due to disturbances in multiple neuronal circuits, especially those associated with the corpus callosum.

    This cross-sectional study aimed to 1) explore the relationships among work-life balance (WLB), burnout, and empathy and 2) investigate the roles of the subtypes of burnout relating to WLB and empathy.

    A total of 105 health care professionals from a general hospital in Seoul were assessed using the Maslach Burnout Inventory, Jefferson Scale of Physician Empathy, and a one-sentence-question on subjective WLB. Multiple questions on psychiatric problems, including sleep problems, anxiety, depressive symptom, and alcohol problems, were also included.

    In the mediation analyses, personal achievement was considered as a potential mediating variable between WLB and empathy. The direct effect (β=3.93, 95% CI 1.21-6.64) and the indirect effect (β=1.95, 95% CI 0.52-3.76) of WLB on empathy were also significant.

    Interventions encouraging personal achievement may help mitigate burnout of health professionals.

    Interventions encouraging personal achievement may help mitigate burnout of health professionals.Hydroureteronephrosis with acute urinary tract obstruction can lead to serious complications such as obstructive nephropathy or pyelonephritis. We report the first case of hydroureteronephrosis caused by a giant fecaloma in an 83-year-old woman accompanied with chronic constipation in Korea. The patient with a fever presented to the emergency room and was diagnosed with right hydronephrosis. Computed tomography revealed a markedly dilated rectum with a giant fecaloma compressing the right vesicoureteric junction. Hydroureteronephrosis was resolved through manual disimpaction of the fecaloma and simultaneous lavage with rectal tubes, which improved the acute pyelonephritis and renal function. Chronic constipation can lead to giant fecaloma threatening urinary tract patency, especially in older patients with immobility or dehydration. Therefore, clinicians should consider this condition as a rare but possible cause of hydronephrosis in older adult patients with chronic constipation.

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