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1.
Nature ; 630(8016): 493-500, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38718835

RESUMEN

The introduction of AlphaFold 21 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design2-6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.37,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.


Asunto(s)
Aprendizaje Profundo , Ligandos , Modelos Moleculares , Proteínas , Programas Informáticos , Humanos , Anticuerpos/química , Anticuerpos/metabolismo , Antígenos/metabolismo , Antígenos/química , Aprendizaje Profundo/normas , Iones/química , Iones/metabolismo , Simulación del Acoplamiento Molecular , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Unión Proteica , Conformación Proteica , Proteínas/química , Proteínas/metabolismo , Reproducibilidad de los Resultados , Programas Informáticos/normas
2.
BMC Psychiatry ; 23(1): 554, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37528355

RESUMEN

BACKGROUND: The treatment efficacy varies across individual patients with major depressive disorder (MDD). It lacks robust electroencephalography (EEG) markers for an antidepressant-responsive phenotype. METHOD: This is an observational study enrolling 28 patients with MDD and 33 healthy controls (mean age of 40.7 years, and 71.4% were women). Patients underwent EEG exams at baseline (week0) and week1, while controls' EEG recordings were acquired only at week0. A resting eye-closing EEG segment was analyzed for functional connectivity (FC). Four parameters were used in FC analysis: (1) node strength (NS), (2) global efficiency (GE), (3) clustering coefficient (CC), and (4) betweenness centrality (BC). RESULTS: We found that controls had higher values in delta wave in the indices of NS, GE, BC, and CC than MDD patients at baseline. After treatment with antidepressants, patients' FC indices improved significantly, including GE, mean CC, and mean NS in the delta wave. The FC in the alpha and beta bands of the responders were higher than those of the non-responders. CONCLUSIONS: The FC of the MDD patients at baseline without treatment was worse than that of controls. After treatment, the FC improved and was close to the values of controls. Responders showed better FC in the high-frequency bands than non-responders, and this feature exists in both pre-treatment and post-treatment EEG.


Asunto(s)
Trastorno Depresivo Mayor , Femenino , Masculino , Humanos , Trastorno Depresivo Mayor/terapia , Depresión , Electroencefalografía , Antidepresivos/uso terapéutico , Biomarcadores , Encéfalo
3.
J Formos Med Assoc ; 121(8): 1384-1391, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34654583

RESUMEN

BACKGROUND/PURPOSE: During pandemics like SARS-CoV-2, healthcare providers' well-being and morale are in particular at stake. Burnout may substantially hinder the well-being and morale of healthcare providers, challenging our efforts at disease containment. This study investigated the relationship between perceived COVID-19 stigma and burnout symptoms among physicians and nurses. We further aimed to identify potential factors that may moderate this relationship, including profession, clinical contact with COVID-19 patients, and prior experience with 2003 SARS-CoV-1. METHODS: We used a web-based, structured survey from March 12th to 29th, 2020 to collect cross-sectional, self-reported data. Participants were provided with a link to the survey which took them on average 5-8 minutes. Survey consisted of demographic characteristics, clinical experiences, perceived COVID-19 related stigma, and burnout symptoms. Linear regression with bootstrapping techniques was adopted to test the relations between stigma and burnout, as well as other potential moderators, while adjusting for demographic and clinical factors. RESULTS: Of the 1421 consented respondents, 357 identified as physicians while 1064 identified as nurses. Participants reported some levels of stigma, and noticeable burnout symptoms. Burnout symptoms were positively correlated with COVID-19 stigma, profession, and currently care for confirmed/suspected COVID-19 patients. The interaction between stigma and profession (Stigma × Nurses) but no other interaction terms reached the significance level, suggesting that the slope for nurses was flatter than the slope for physicians. CONCLUSION: The study results suggest that COVID-19 stigma may contribute to burnout among physicians and nurses, and this relation may not vary across clinical roles and experiences but profession.


Asunto(s)
Agotamiento Profesional , COVID-19 , Enfermeras y Enfermeros , Médicos , Agotamiento Profesional/epidemiología , Agotamiento Psicológico , Estudios Transversales , Personal de Salud , Humanos , SARS-CoV-2 , Encuestas y Cuestionarios
4.
BMC Psychiatry ; 20(1): 376, 2020 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-32677926

RESUMEN

BACKGROUND: It is hypothesized that anxiety and behavioral responses are intense at the beginning of an epidemic. The objective of this study was to investigate anxiety symptoms and use of preventive measures against COVID-19. The study also compared the association between preventive measures and anxiety symptoms during the week immediately preceding the study and those symptoms and measures at the beginning of the outbreak. METHODS: A cross-sectional population survey using an online questionnaire commenced on 14 February 2020. The study participants were residents of Taiwan ages 20 to 70 years. The 6-item state version of the State-Trait Anxiety Inventory (STAI-6) was used to assess anxiety symptoms. The questions about preventive measures asked participants about their personal protection, cough etiquette, contact precautions, voluntary quarantine, and prompt reporting. Multivariable logistic regression was used to determine the factors influencing an increase in the preventive measures scores. RESULTS: Of a total of 3555 completed responses, a total of 52.1% (95% confidence interval [CI] 50.4-53.7) of the respondents reported moderate to severe levels of anxiety symptoms in the past week, whereas 48.8% (95%CI 47.2-50.5) reported moderate to severe anxiety symptoms at the beginning of the outbreak. With a higher score indicating greater anxiety, the median scores for anxiety symptoms in the past week and at the beginning of the outbreak were 46.7 (IQR [interquartile range] 36.7-53.3) and 43.3 (IQR 36.7-53.3), respectively. The median scores for the preventive measures taken in the past week and at the beginning of the outbreak were 26.0 (IQR 21.0-30.0) and 24.0 (IQR 19.0-28.0), respectively, out of a maximum score of 36. In the multivariable analysis, an increased anxiety symptom score from the beginning of the outbreak to the past week (adjusted OR = 7.38, 95%CI 6.28-8.66) was a strongly significant determinant of an increased preventive measures score in the past week compared with the score at the beginning of the outbreak. CONCLUSIONS: Anxiety and preventive measures scores were high and increased with the epidemic rate. Higher anxiety was associated with an increased use of preventive measures against COVID-19.


Asunto(s)
Ansiedad/psicología , Infecciones por Coronavirus/prevención & control , Conductas Relacionadas con la Salud , Pandemias/prevención & control , Equipo de Protección Personal , Neumonía Viral/prevención & control , Cuarentena , Adulto , Anciano , Ansiedad/epidemiología , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/epidemiología , Estudios Transversales , Brotes de Enfermedades , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neumonía Viral/epidemiología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Taiwán/epidemiología , Adulto Joven
5.
BMC Psychiatry ; 20(1): 346, 2020 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-32616019

RESUMEN

AIMS: The study aims were to investigate adherence to methadone maintenance treatment (MMT) and to identify associated clinical factors in patients who inject drugs diagnosed with human immunodeficiency virus (HIV) infection in Taiwan. METHODS: Data were from the National Health Surveillance System on HIV and the National Drug Treatment System on MMT. HIV-positive people who inject drugs (HIVPWID) were defined as the study population. Information obtained included age, sex, education, marital status, employment, methadone dose, and date of diagnosis of HIV infection. Adherence was defined as taking methadone for the past 90, 180 and 365 days, then categorized as high (> 90%), moderate (51 to 90%), or low (<=50%) adherent respectively. RESULTS: Of 1641 HIVPWID registered in the datasets from 2007 to 2012, 961 (58.56%) had received MMT. For HIVPWID evaluated at 90 days (n = 951), 271 (28.5%), 382 (40.2%), and 298 (31.3%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 180 days (n = 936), 190 (20.3%), 349 (37.3%), and 397 (42.4%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 365 days (n = 919), 133 (14.5%), 271 (29.5%), and 515 (56.0%) were classified as high, moderate, and low adherent respectively. After controlling for sociodemographics, results showed that methadone dose, location of MMT clinic, and date of HIV diagnosis were significantly associated with MMT adherence. CONCLUSIONS: Study findings underscore the importance to MMT adherence of methadone dosage, early diagnosis of patient's HIV infection, and area of patient residence.


Asunto(s)
Consumidores de Drogas , Infecciones por VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Taiwán
6.
Am J Drug Alcohol Abuse ; 46(1): 31-43, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31264888

RESUMEN

Background: The striatum supports motivated behavior and impulse control. Altered striatal activation and connectivity has been observed in link with impulse control dysfunction in individuals with drug addiction.Objectives: We examined how resting state functional connectivity (rsFC) of the striatum is altered as a result of chronic ketamine misuse.Methods: Thirty-six ketamine users (10 women) and 20 healthy controls (9 women) completed an assessment with the Barratt Impulsiveness Scale (BIS-11) and magnetic resonance imaging. In SPM we examined voxel-wise connectivities of the caudate, pallidum, putamen, and ventral striatum in ketamine users (versus healthy controls) and in association with BIS-11 score and duration of use, all at a corrected threshold.Results: Compared to controls, ketamine users showed higher connectivity between caudate and dorsal anterior cingulate cortex and between pallidum and bilateral cerebellum. In ketamine users, putamen showed higher connectivity with the left orbitofrontal cortex (OFC) in association with both BIS-11 score and months of ketamine use. Mediation analyses suggest that the connectivity z score mediated the relationship between impulsivity and duration of use.Conclusions: These preliminary findings highlighted altered striatal connectivity in chronic ketamine users, and the potential role of putamen OFC connectivity in supporting the correlation between impulsivity and duration of ketamine use. If replicated in a larger sample, these findings may represent neural markers of ketamine misuse.


Asunto(s)
Consumidores de Drogas , Conducta Impulsiva , Ketamina/efectos adversos , Estriado Ventral/efectos de los fármacos , Estriado Ventral/fisiopatología , Adulto , Femenino , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Análisis de Mediación , Proyectos Piloto , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Taiwán/epidemiología , Adulto Joven
7.
Proc Natl Acad Sci U S A ; 112(29): 9123-8, 2015 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-26150519

RESUMEN

Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.


Asunto(s)
Encéfalo/fisiopatología , Endofenotipos/metabolismo , Red Nerviosa/fisiopatología , Resiliencia Psicológica , Esquizofrenia/fisiopatología , Adulto , Análisis por Conglomerados , Demografía , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Análisis de Ondículas
9.
Magn Reson Med ; 78(1): 387-398, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-27501382

RESUMEN

PURPOSE: The common marmoset (Callithrix jacchus) is a New World primate of increasing interest to neuroscience and in translational brain research. The present work describes the design and implementation of individualized 8-channel receive-only radiofrequency (RF) coil arrays that provide whole-brain coverage and allow anatomical and functional MRI experiments in conscious, awake marmosets. METHODS: The coil arrays were designed with their elements embedded inside individualized restraint helmets. The size, geometry, and arrangement of the coil elements were optimized to allow whole-brain coverage. Coil-to-coil decoupling was achieved by a combination of geometric decoupling and low input impedance preamplifiers. The performance of the embedded arrays was compared against that of one 8-channel receive-only array built to fit the external surface of the helmets. RESULTS: Three individualized helmets with embedded coil arrays were built for three marmosets. Whole-brain coverage was achieved with high sensitivity extending over the entire cortex. Visual stimulation of conscious awake marmosets elicited robust BOLD fMRI responses in both primary and higher order visual areas of the occipitotemporal cortex. CONCLUSION: The high sensitivity provided by embedded receive-only coil arrays allows both anatomical and functional MRI data to be obtained with high spatial resolution in conscious, awake marmosets. Magn Reson Med 78:387-398, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Asunto(s)
Mapeo Encefálico/instrumentación , Mapeo Encefálico/veterinaria , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/veterinaria , Transductores/veterinaria , Corteza Visual/anatomía & histología , Corteza Visual/fisiología , Animales , Callithrix , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de Equipo , Aumento de la Imagen/instrumentación , Masculino , Estimulación Luminosa/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Vigilia
10.
J Neurosci ; 35(3): 1160-72, 2015 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-25609630

RESUMEN

The cerebral cortex of humans and macaques has specialized regions for processing faces and other visual stimulus categories. It is unknown whether a similar functional organization exists in New World monkeys, such as the common marmoset (Callithrix jacchus), a species of growing interest as a primate model in neuroscience. To address this question, we measured selective neural responses in the brain of four awake marmosets trained to fix their gaze upon images of faces, bodies, objects, and control patterns. In two of the subjects, we measured high gamma-range field potentials from electrocorticography arrays implanted over a large portion of the occipital and inferotemporal cortex. In the other two subjects, we measured BOLD fMRI responses across the entire brain. Both techniques revealed robust, regionally specific patterns of category-selective neural responses. We report that at least six face-selective patches mark the occipitotemporal pathway of the marmoset, with the most anterior patches showing the strongest preference for faces over other stimuli. The similar appearance of these patches to previous findings in macaques and humans, including their apparent arrangement in two parallel pathways, suggests that core elements of the face processing network were present in the common anthropoid primate ancestor living ∼35 million years ago. The findings also identify the marmoset as a viable animal model system for studying specialized neural mechanisms related to high-level social visual perception in humans.


Asunto(s)
Corteza Visual/fisiología , Percepción Visual/fisiología , Animales , Mapeo Encefálico , Callithrix , Cara , Neuroimagen Funcional , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa
12.
Neuroimage ; 120: 1-11, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26149609

RESUMEN

The visual brain is composed of interconnected subcortical and cortical structures that receive and process image information originating in the retina. The visual system of nonhuman primates, in particular macaques, has been studied in great detail in order to elucidate principles of human sensation and perception. The common marmoset (Callithrix jacchus) is a small New World monkey of growing interest as a primate model for neuroscience. Marmosets have advantages over macaques because of their small size, lissencephalic cortex, and growing potential for viral and genetic manipulations. Previous anatomical studies and electrophysiological recordings in anesthetized marmosets have shown that this species' cortical visual hierarchy closely resembles that of other primates, including humans. Until now, however, there have been no attempts to systematically study visual responses throughout the marmoset brain using fMRI. Here we show that awake marmosets readily learn to carry out a simple visual task inside the bore of an MRI scanner during functional mapping experiments. Functional scanning at 500 µm in-plane resolution in a 30 cm horizontal bore at 7 T revealed robust positive blood oxygenation level-dependent (BOLD) fMRI responses to visual stimuli throughout visual cortex and associated subcortical areas. Nonvisual sensory areas showed negative contrasts to visual stimuli compared to the fixation dot only baseline. Structured images of objects and faces led to stronger responses than scrambled control images at stages beyond early visual cortex. Our study establishes fMRI mapping of visual responses in awake, behaving marmosets as a straightforward and valuable tool for assessing the functional organization of the primate brain at high resolution.


Asunto(s)
Conducta Animal/fisiología , Mapeo Encefálico/métodos , Encéfalo/fisiología , Callithrix/fisiología , Imagen por Resonancia Magnética/métodos , Reconocimiento Visual de Modelos/fisiología , Animales , Masculino
13.
Org Biomol Chem ; 12(27): 4890-904, 2014 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-24874710

RESUMEN

We report the results of attaching the anticancer drug chlorambucil (CLB) to two high-affinity DNA binding peptides: Met-Hyp-Arg-Lys-(Py)4-Lys-Arg-NH2 (HyM-10) and Gln-Hyp-Arg-Lys-(Py)4-Lys-Arg-NH2 (HyQ-10). These CLB-peptide conjugates cleave DNA very effectively and sequence-selectively without the use of chemicals, heat, or UV irradiation. Polyacrylamide gel electrophoresis identifies the sites where CLB-HyM-10 and CLB-HyQ-10 attack a complementary pair of 5'-(32)P-labeled duplexes derived from pBR322 in the absence of piperidine or other chemical additives. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has confirmed the preferential cleavage sites as well as a novel stepwise cleavage mechanism of sequence-selective DNA cleavage. Resembling restriction endonucleases, the CLB-peptide conjugates appear to be capable of producing double strand DNA breaks. Circular dichroism studies show that CLB-HyM-10 and CLB-HyQ-10 induce significant local conformational changes in DNA via the minor groove, possibly with dimeric binding stoichiometry. The energetic basis of DNA binding by these conjugates has been investigated by isothermal titration calorimetry, revealing that the binding of both the peptides and their CLB conjugates is overwhelmingly enthalpy-driven. The maintenance of a conserved negative binding free energy in DNA-conjugate interactions is a crucial feature of the universal enthalpy-entropy compensation phenomenon. The strongly enthalpy-driven binding of CLB-peptide conjugates to preferred loci in DNA furnishes the required proximity effect to generate the observed nuclease-like sequence-selective cleavage.


Asunto(s)
Clorambucilo/metabolismo , Desoxirribonucleasas/metabolismo , Péptidos/metabolismo , Termodinámica , ADN/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
14.
Nano Lett ; 13(9): 4118-22, 2013 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-23930914

RESUMEN

We report the transport and trapping behavior of 100 and 500 nm diameter nanospheres in a plasmon-enhanced two-dimensional optical lattice. An optical potential is created by a two-dimensional square lattice of gold nanostructures, illuminated by a Gaussian beam to excite plasmon resonance. The nanoparticles can be guided, trapped, and arranged using this optical potential. Stacking of 500 nm nanospheres into a predominantly hexagonal closed pack crystalline structure under such a potential is also reported.

15.
Am J Geriatr Psychiatry ; 21(8): 811-5, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23567390

RESUMEN

OBJECTIVES: Selective serotonin reuptake inhibitor (SSRI) exposure has controversial results in increasing the stroke risk. With the risk of stroke increased with age, the safety of SSRI use among older adults attracts much concern. METHODS: We analyzed 28,145 subjects older than 65 years from a subset of a 9-year cohort database from the National Health Insurance Research Database, Taiwan. RESULTS: The survival analysis showed a greater probability of stroke in subjects with SSRI exposure after adjusting other covariates. Compared with other variables, SSRI exposure had the strongest effect (hazard ratio: 2.66, 95% confidence interval: 2.21-3.20). The risk was independent to depression-related stroke risk. CONCLUSIONS: The use of SSRIs independently increases the risk of stroke among older patients. SSRIs are still practically safe to most users, providing precautionary measures are taken.


Asunto(s)
Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Masculino , Taiwán/epidemiología
16.
Org Biomol Chem ; 11(1): 48-61, 2013 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-23051861

RESUMEN

This study aims to interpret the energetic basis of complex DNA-peptide interactions according to a novel allosteric interaction network approach. In common with other designed peptides, five new conjugates incorporating the XPRK or XHypRK motif (Hyp = hydroxyproline) attached to a N-methylpyrrole (Py) tract with a basic tail have been found to display cooperative binding to DNA involving multiple monodentate as well as interstrand bidentate interactions. Using quantitative DNase I footprinting it appears that allosteric communication via cooperative binding to multiple sites on complementary DNA strands corresponds to two different types of DNA-peptide interaction network. Temperature variation experiments using a dodecapeptide RY-12 show that lower temperature (25 °C) favor a circuit type of allosteric interaction network, whereas higher temperatures (31 and 37 °C) afford only a partial-circuit type of network. Circular dichroism studies show that our five peptides induce significant local conformational changes in DNA via the minor groove, with apparently dimeric binding stoichiometry. Isothermal titration calorimetry reveals that these peptides, together with another seven for comparison, are strongly exothermic upon binding to a model 13-mer DNA duplex, characterized by ΔH ranging from -14.7 to -74.4 kcal mol(-1), and also high TΔS ranging from -6.5 to -65.9 kcal mol(-1). Multiple monodentate and bidentate interactions, as well as ionic forces that mediate positive cooperativity in sequence recognition, are consistent with a dramatic decrease in entropy and a 'tightening' effect of DNA conformation. Distinctive enthalpy-entropy compensation (EEC) relationships are demonstrated for the interaction of all twelve designed peptides with DNA, affording a straight line of slope close to unity when ΔH is plotted versus TΔS, with a y-axis intercept (average ΔG) corresponding to -8.5 kcal mol(-1), while the observed ΔG ranges from -8.2 to -9.1 kcal mol(-1) for the peptides. The EEC seen with peptide RY-12 binding to the model duplex persists throughout various incubation temperatures. The net compensation of energy between the favorable negative ΔH and unfavorable negative ΔS components thus constrains the value of net binding free energy ΔG within a remarkably constant range, as is clearly visible in a 3-dimensional energetic plot. We conclude that the preservation of a rather narrowly-defined ΔG value is central to the EEC in DNA-peptide interactions, illuminating the universal EEC paradox commonly found in diverse biochemical reactions.


Asunto(s)
ADN/química , Péptidos/química , Termodinámica
17.
Front Public Health ; 11: 1066908, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36844831

RESUMEN

Background: Improper or insufficient treatment of mental health illness harms individuals, families, and society. When psychiatric treatment shifts from a hospital-based to a community-based health care system, risk management is essential to the provision of effective care. Objective: We examine whether an upgrade in home visit frequency of psychiatric patients as identified by public health nurses can predict the subsequent need for emergency escort services for medical treatment. Design: A 2-year retrospective medical record review. Settings: A district of New Taipei City in Taiwan. Participants: A total of 425 patients with a diagnosed mental health illness cared for through home visits by public health nurses from January 2018 to December 2019. Methods: We accessed the Ministry of Health and Welfare's psychiatric care management information system to identify a set of medical records, and analyzed these records using chi-square and regression analyses. Results: The analyses indicated that the groups experiencing the greatest need for emergency escort services were: male, 35-49 years old, with a senior high school level of education, without a disability identification card, with a schizophrenia diagnosis, and had been reported by the nurse as having progressed to a serious level. Nurses' increased frequency of home visits (an indicator that the patient's overall condition was worsening) and nurses' reports of increased severity of problems were significant predictors of the need for emergency escort services. Conclusions: The nurses' adjustment of visit frequency based on the results of the visit assessment predicts the need for emergency escort services for mental patients. The findings support not only the professional roles and functions of public health nurses, but also the importance of strengthening psychiatric health community support services.


Asunto(s)
Trastornos Mentales , Enfermeras de Salud Pública , Humanos , Masculino , Adulto , Persona de Mediana Edad , Visita Domiciliaria , Estudios Retrospectivos , Trastornos Mentales/terapia , Registros Médicos
18.
Life Sci ; 301: 120624, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35568225

RESUMEN

AIMS: To study effects on cellular innate immune responses to ORF8, ORF10, and Membrane protein (M protein) from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, in combination with cannabidiol (CBD). MAIN METHODS: HEK293 cells transfected with plasmids expressing control vector, ORF8, ORF10, or M protein were assayed for cell number and markers of apoptosis at 24 h, and interferon and interferon-stimulated gene expression at 14 h, with or without CBD. Cells transfected with polyinosinic:polycytidylic acid (Poly (I:C)) were also studied as a general model of RNA-type viral infection. KEY FINDINGS: Reduced cell number and increased early and late apoptosis were found when expression of viral genes was combined with 1-2 µM CBD treatment, but not in control-transfected cells treated with CBD, or in cells expressing viral genes but treated only with vehicle. In cells expressing viral genes, CBD augmented expression of IFNγ, IFNλ1 and IFNλ2/3, as well as the 2'-5'-oligoadenylate synthetase (OAS) family members OAS1, OAS2, OAS3, and OASL. CBD also augmented expression of these genes in control cells not expressing viral genes, but without enhancing apoptosis. CBD similarly enhanced the cellular anti-viral response to Poly (I:C). SIGNIFICANCE: Our results demonstrate a poor ability of HEK293 cells to respond to SARS-CoV-2 genes alone, but an augmented innate anti-viral response to these genes in the presence of CBD. Thus, CBD may prime components of the innate immune system, increasing readiness to respond to RNA-type viral infection without activating apoptosis, and could be studied for potential in prophylaxis.


Asunto(s)
COVID-19 , Cannabidiol , Antivirales , Apoptosis , Cannabidiol/farmacología , Células HEK293 , Humanos , Inmunidad Innata/genética , Interferones/farmacología , Proteínas de la Membrana , Poli I-C/farmacología , ARN , SARS-CoV-2
19.
Sci Rep ; 12(1): 801, 2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-35039593

RESUMEN

This study aims to depict and compare clinical characteristics and risk behavior among groups of individuals using ketamine, polydrugs or smoking cigarette. A total of 185 drug-using participants and 49 smokers participated in this study. A cross-sectional interview was used to collect information on demographics, drug- and sex-related behaviors, HIV serostatus, lower urinary tract symptoms (LUTS), behavioral dispositions. N-back memory test was used to measure short-term memory. Result shows that 10 participants (5.41%) were HIV positive and 14 (7.57%) having LUTS. Individuals with ketamine and polydrugs use have significantly worse drug-related problem than cigarette smokers. Compared to cigarette smokers and ketamine users, individuals with polydrug users scored significantly higher on impulsivity measures. Cigarette smokers performed significantly better than the other two groups on the memory tests. A few patients had been infected with HIV and diagnosed with LUTS. Findings support that memory on short term recalls of patients with ketamine use might be impaired. Study findings warrants the necessarily of further study on influences of using ketamine.


Asunto(s)
Conducta Impulsiva , Ketamina/efectos adversos , Memoria a Corto Plazo , Asunción de Riesgos , Conducta Sexual , Trastornos Relacionados con Sustancias/etiología , Trastornos Relacionados con Sustancias/psicología , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Síntomas del Sistema Urinario Inferior/inducido químicamente , Masculino , Fumar/efectos adversos , Adulto Joven
20.
J Microbiol Immunol Infect ; 55(6 Pt 1): 1044-1051, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35995669

RESUMEN

BACKGROUND/PURPOSE: Predictors for out-of-hospital cardiac arrest (OHCA) in COVID-19 patients remain unclear. We identified the predictors for OHCA and in-hospital mortality among such patients in community isolation centers. METHODS: From May 15 to June 20, 2021, this cohort study recruited 2555 laboratory-confirmed COVID-19 patients admitted to isolation centers in Taiwan. All patients were followed up until death, discharge from the isolation center or hospital, or July 16, 2021. OHCA was defined as cardiac arrest confirmed by the absence of circulation signs and occurring outside the hospital. Multinomial logistic regressions were used to determine factors associated with OHCA and in-hospital mortality. RESULTS: Of the 37 deceased patients, 7 (18.9%) had OHCA and 30 (81.1%) showed in-hospital mortality. The mean (SD) time to OHCA was 6.6 (3.3) days from the symptom onset. After adjusting for demographics and comorbidities, independent predictors for OHCA included age ≥65 years (adjusted odds ratio [AOR]: 13.24, 95% confidence interval [CI]: 1.85-94.82), fever on admission to the isolation center (AOR: 12.53, 95% CI: 1.68-93.34), and hypoxemia (an oxygen saturation level below 95% on room air) (AOR: 26.54, 95% CI: 3.18-221.73). Predictors for in-hospital mortality included age ≥65 years (AOR: 10.28, 95% CI: 2.95-35.90), fever on admission to the isolation centers (AOR: 7.27, 95% CI: 1.90-27.83), and hypoxemia (AOR: 29.87, 95% CI: 10.17-87.76). CONCLUSIONS: Time to OHCA occurrence is rapid in COVID-19 patients. Close monitoring of patients' vital signs and disease severity during isolation is important, particularly for those with older age, fever, and hypoxemia.


Asunto(s)
COVID-19 , Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Humanos , Anciano , Paro Cardíaco Extrahospitalario/epidemiología , Estudios Retrospectivos , Estudios de Cohortes , Mortalidad Hospitalaria , Hipoxia/epidemiología
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