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1.
Mol Psychiatry ; 28(3): 1079-1089, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36653677

RESUMO

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.


Assuntos
Fobia Social , Adulto , Adolescente , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Ansiedade , Neuroimagem/métodos
2.
Langmuir ; 39(9): 3462-3470, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36827550

RESUMO

Carbon-fluorine bonds in fluorinated molecules can undergo homolytic cleavage reactions when electrons are injected, and the resulting radicals combine to form network structures characterized by reduced solubility. This crosslinking chemistry suggests a new category of patterning materials that function under electron beam (e-beam) and extreme ultraviolet (EUV) lithographic conditions. Although this chemistry enables the production of 50 nm or smaller-sized features of simple fluoroalkylated polymers, it is limited by the need for relatively large amounts of irradiation energy to achieve required solubility changes. Therefore, this study was undertaken to devise a sensitivity-enhancing strategy based on a synergistic combination of radical crosslinking and hydrogen-bonding interactions between highly fluoroalkylated copolymers. An alternating copolymer was synthesized using tert-butoxystyrene and a fluoroalkylated maleimide, the former of which produces active hydrogens through catalytic acidolysis reactions. When the polymer was blended with a catalytic amount of a photoacid generator and subjected to lithographic patterning tests under e-beam and EUV irradiation, the deprotection reactions of tert-butoxy moieties proceeded at room temperature and led to a solubility decrease. We presume the small number of hydroxyl moieties produced formed an intermolecular hydrogen-bonding network, which acted synergistically with the covalent crosslinks generated by C-F bonds. When 30 nm features of copolymer thin films were fabricated by EUV lithography, sensitivity was improved by 25-34% without significant deterioration of pattern quality, especially line-edge roughness. These results demonstrate that EUV resists with improved patterning capabilities can be achieved by combining catalytic acidolysis reactions and noncatalytic crosslinking chemistry.

3.
Am J Addict ; 30(1): 72-79, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33232571

RESUMO

BACKGROUND AND OBJECTIVES: Substance use disorder (SUD) includes maladaptive patterns of substance use despite negative consequences. Previous structural neuroimaging studies showed some structural alterations in SUD, but it remains unknown whether these alterations are specifically associated with SUD or common comorbidities. This study attempts to validate the findings of structural differences between SUD, healthy controls (HC), and psychiatric controls (PC). METHODS: We used HC (N = 86) matched for demographics, and PC (N = 86) matched for demographics and psychiatric diagnoses to a group of SUD patients (N = 86). We assessed the group differences of subcortical volumes, cortical volumes, thickness, and surface areas between SUD and HC. We then analyzed the group differences between SUD and PC within regions showing differences between SUD and HC. RESULTS: SUD had smaller left nucleus accumbens, right thalamus, right hippocampus, left caudal anterior cingulate cortex (ACC) volume, and larger right caudal ACC volume, and right caudal ACC, right caudal middle frontal gyrus (MFG), and right posterior cingulate cortex (PCC) surface than HC. Increased right caudal ACC volume and right PCC surface in SUD were the only findings when compared with PC. Several areas showed thickness alterations between SUD and HC, but none survived multiple comparisons vs PC. DISCUSSION AND CONCLUSIONS: Our findings suggest that cingulate structures may be altered in SUD compared with both HC and PC. SCIENTIFIC SIGNIFICANCE: These results are among the first to indicate that some structural alterations may be SUD-specific, and highlight a cautionary note about using HC in psychiatric biomarker research. (Am J Addict 2021;30:72-79).


Assuntos
Encéfalo/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Adolescente , Adulto , Encéfalo/patologia , Estudos de Casos e Controles , Comorbidade , Feminino , Giro do Cíngulo/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Pacientes Internados , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/patologia , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Neuroimagem , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/patologia , Tamanho do Órgão , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Adulto Jovem
4.
Biotechnol Bioeng ; 115(2): 278-289, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28782813

RESUMO

Antibacterial resistance is an issue of increasing severity as current antibiotics are losing their effectiveness and fewer antibiotics are being developed. New methods for combating bacterial virulence are required. Modulating molecular communication among bacteria can alter phenotype, including attachment to epithelia, biofilm formation, and even toxin production. Intercepting and modulating communication networks provide a means to attenuate virulence without directly interacting with the bacteria of interest. In this work, we target communication mediated by the quorum sensing (QS) bacterial autoinducer-2, AI-2. We have assembled a capsule of biological polymers alginate and chitosan, attached an AI-2 processing kinase, LsrK, and provided substrate, ATP, for enzymatic alteration of AI-2 in culture fluids. Correspondingly, AI-2 mediated QS activity is diminished. All components of this system are "biofabricated"-they are biologically derived and their assembly is accomplished using biological means. Initially, component quantities and kinetics were tested as assembled in microtiter plates. Subsequently, the identical components and assembly means were used to create the "artificial cell" capsules. The functionalized capsules, when introduced into populations of bacteria, alter the dynamics of the AI-2 bacterial communication, attenuating QS activated phenotypes. We envision the assembly of these and other capsules or similar materials, as means to alter QS activity in a biologically compatible manner and in many environments, including in humans.


Assuntos
Células Artificiais/metabolismo , Biopolímeros/química , Proteínas de Escherichia coli/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Percepção de Quorum/genética , Proteínas Recombinantes/metabolismo , Alginatos/química , Células Artificiais/química , Quitosana/química , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Homosserina/análogos & derivados , Homosserina/química , Homosserina/metabolismo , Lactonas/química , Lactonas/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Plasmídeos/genética , Proteínas Recombinantes/genética
5.
Adv Funct Mater ; 26(20): 3382-3393, 2016 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-27375374

RESUMO

When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve oral delivery of NCs to treat gastrointestinal (GI) pathologies or for systemic absoption. However, GI instability of targeting moieties compromises this strategy. We explored whether encapsulation of antibody-coated NCs in microcapsules would protect against gastric degradation, providing NCs release and targeting in intestinal conditions. We used nanoparticles coated with antibodies against intercellular adhesion molecule-1 (anti-ICAM) or non-specific IgG. NCs (~160-nm) were encapsulated in ~180-µm microcapsules with an alginate core, in the absence or presence of a chitosan shell. We found >95% NC encapsulation within microcapsules and <10% NC release from microcapsules in storage. There was minimal NC release at gastric pH (<10%) and burst release at intestinal pH (75-85%), slightly attenuated by chitosan. Encapsulated NCs afforded increased protection against degradation (3-4 fold) and increased cell targeting (8-20 fold) after release vs. non-encapsulated NCs. Mouse oral gavage showed that microencapsulation provided 38-65% greater protection of anti-ICAM NCs in the GI tract, 40% lower gastric retention, and 4-9-fold enhanced intestinal biodistribution vs. non-encapsulated NCs. Therefore, microencapsulation of antibody-targeted NCs may enable active targeting strategies to be effective in the context of oral drug delivery.

6.
J Am Chem Soc ; 137(17): 5819-27, 2015 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-25871426

RESUMO

The ability to modulate the physical properties of a supramolecular hydrogel may be beneficial for biomaterial and biomedical applications. We find that guanosine (G 1), when combined with 0.5 equiv of potassium borate, forms a strong, self-supporting hydrogel with elastic moduli >10 kPa. The countercation in the borate salt (MB(OH)4) significantly alters the physical properties of the hydrogel. The gelator combination of G 1 and KB(OH)4 formed the strongest hydrogel, while the weakest system was obtained with LiB(OH)4, as judged by (1)H NMR and rheology. Data from powder XRD, (1)H double-quantum solid-state magic-angle spinning (MAS) NMR and small-angle neutron scattering (SANS) were consistent with a structural model that involves formation of borate dimers and G4·K(+) quartets by G 1 and KB(OH)4. Stacking of these G4·M(+) quartets into G4-nanowires gives a hydrogel. We found that the M(+) cation helps stabilize the anionic guanosine-borate (GB) diesters, as well as the G4-quartets. Supplementing the standard gelator mixture of G 1 and 0.5 equiv of KB(OH)4 with additional KCl or KNO3 increased the strength of the hydrogel. We found that thioflavin T fluoresces in the presence of G4·M(+) precursor structures. This fluorescence response for thioflavin T was the greatest for the K(+) GB system, presumably due to the enhanced interaction of the dye with the more stable G4·K(+) quartets. The fluorescence of thioflavin T increased as a function of gelator concentration with an increase that correlated with the system's gel point, as measured by solution viscosity.


Assuntos
Boratos/química , Guanosina/química , Hidrogéis/química , Metais Alcalinos/química , Compostos Organometálicos/química , Tiazóis/química , Benzotiazóis , Fluorescência , Hidrogéis/síntese química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Organometálicos/síntese química , Prótons
7.
Langmuir ; 31(19): 5259-64, 2015 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-25955654

RESUMO

Molecular organogelators convert oils into gels by forming self-assembled fibrous networks. Here, we demonstrate that such gelation can be activated by contacting the oil with an immiscible solvent (water). Our gelator is dibenzylidene sorbitol (DBS), which forms a low-viscosity sol when added to toluene containing a small amount of dimethyl sulfoxide (DMSO). Upon contact with water, DMSO partitions into the water, activating gelation of DBS in the toluene. The gel grows from the oil/water interface and slowly envelops the oil phase. We have exploited this effect for the self-repair of oil leaks from underwater tubes. When a DBS/toluene/DMSO solution flows through the tube, it forms a gel selectively at the leak point, thereby plugging the leak and restoring flow. Our approach is reminiscent of wound-sealing via blood-clotting: there also, inactive gelators in blood are activated at the wound site into a fibrous network, thereby plugging the wound and restoring blood flow.


Assuntos
Óleos/química , Sorbitol/análogos & derivados , Água/química , Biomimética , Coagulação Sanguínea , Dimetil Sulfóxido/química , Géis/síntese química , Géis/química , Estrutura Molecular , Reologia , Sorbitol/síntese química , Sorbitol/química , Tolueno/química
8.
Langmuir ; 30(34): 10221-30, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25121460

RESUMO

The self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Previous studies on lecithin-bile salt mixtures have reported the formation of short, rodlike micelles. Here, we show that lecithin-bile salt micelles can be further induced to grow into long, flexible wormlike structures. The formation of long worms and their resultant entanglement into transient networks is reflected in the rheology: the fluids become viscoelastic and exhibit Maxwellian behavior, and their zero-shear viscosity can be up to a 1000-fold higher than that of water. The presence of worms is further confirmed by data from small-angle neutron and X-ray scattering and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin, which suggests a strong binding interaction between the two species. In addition, micellar growth also requires a sufficient concentration of background electrolyte such as NaCl or sodium citrate that serves to screen the electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We postulate a mechanism based on changes in the molecular geometry caused by bile salts and electrolytes to explain the micellar growth.


Assuntos
Ácidos e Sais Biliares/química , Lecitinas/química , Micelas , Microscopia Crioeletrônica , Microscopia Eletrônica de Varredura , Espalhamento de Radiação , Soluções , Viscosidade , Água/química
9.
Soft Matter ; 10(15): 2632-40, 2014 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-24647411

RESUMO

Many small molecules can self-assemble by non-covalent interactions into fibrous networks and thereby induce gelation of organic liquids. However, no capability currently exists to predict whether a molecule in a given solvent will form a gel, a low-viscosity solution (sol), or an insoluble precipitate. Gelation has been recognized as a phenomenon that reflects a balance between solubility and insolubility; however, the distinction between these regimes has not been quantified in a systematic fashion. In this work, we focus on a well-known gelator, 1,3:2,4-dibenzylidene sorbitol (DBS), and study its self-assembly in various solvents. From these data, we build a framework for DBS gelation based on Hansen solubility parameters (HSPs). While the HSPs for DBS are not known a priori, the HSPs are available for each solvent and they quantify the solvent's ability to interact via dispersion, dipole-dipole, and hydrogen bonding interactions. Using the three HSPs, we construct three-dimensional plots showing regions of solubility (S), slow gelation (SG), instant gelation (IG), and insolubility (I) for DBS in the different solvents at a given temperature and concentration. Our principal finding is that the above regions radiate out as concentric shells: i.e., a central solubility (S) sphere, followed in order by spheres corresponding to SG, IG, and I regions. The distance (R0) from the origin of the central sphere quantifies the incompatibility between DBS and a solvent-the larger this distance, the more incompatible the pair. The elastic modulus of the final gel increases with R0, while the time required for a super-saturated sol to form a gel decreases with R0. Importantly, if R0 is too small, the gels are weak, but if R0 is too large, insolubility occurs-thus, strong gels fall within an optimal window of incompatibility between the gelator and the solvent. Our approach can be used to design organogels of desired strength and gelation time by judicious choice of a particular solvent or a blend of solvents. The above framework can be readily extended to many other gelators, including those with molecular structures very different from that of DBS. We have developed a MATLAB program that will be freely available (upon request) to the scientific community to replicate and extend this approach to other gelators of interest.

10.
J Neonatal Nurs ; 20(4): 178-188, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25018662

RESUMO

The precocial nature of orofacial sensorimotor control underscores the biological importance of establishing ororythmic activity in human infants. The purpose of this study was to assess the effects of comparable doses of three forms of orosensory experience, including a low-velocity spectrally reduced orocutaneous stimulus (NT1), a high-velocity broad spectrum orocutaneous stimulus (NT2), and a SHAM stimulus consisting of a blind pacifier. Each orosensory experience condition was paired with gavage feedings 3x/day for 10 days in the neonatal intensive care unit (NICU). Four groups of preterm infants (N=214), including those with respiratory distress syndrome (RDS), chronic lung disease (CLD), infants of diabetic mothers (IDM), and healthy controls (HI) were randomized to the type of orosensory condition. Mixed modeling, adjusted for gender, gestational age, postmenstrual age, and birth weight, demonstrated the most significant gains in non-nutritive suck (NNS) development among CLD infants who were treated with the NT2 stimulus, with smaller gains realized among RDS and IDM infants. The broader spectrum of the NT2 stimulus maps closely to known response properties of mechanoreceptors in lip, tongue, and oral mucosa and is more effective in promoting NNS development among preterm infants with impaired oromotor function compared to the low-velocity, spectrally reduced NT1 orosensory stimulus.

11.
Drug Alcohol Depend ; 256: 111097, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266574

RESUMO

BACKGROUND: Substance misuse is a major public health issue and research has established attenuated reward responses to drug cues in those who misuse substances. Yet, little is known about whether the expectation of natural reinforcers engages distinct brain regions in substance misuse. METHODS: Using functional magnetic resonance imaging (fMRI), we delivered juice at expected and unexpected times to examine reward processing dysfunctions. We focused on the responses within the left dorsal striatum (DS) in individuals with high-risk substance use (HRU, n = 65), low-risk substance use (psychiatric controls, PC, n = 65), and healthy controls (HC, n = 65). Additionally, we investigated whether the dysfunction in reward processing within the left DS is correlated with other common psychiatric symptoms. Finally, we conducted a comprehensive analysis of the whole brain to investigate other non-hypothesized brain regions. RESULTS: Compared to HC, HRU displayed lower responses to juice delivery (i.e., reward) in the left DS (p <.05). The whole-brain analysis demonstrated that compared to HC, HRU displayed significantly lower responses to reward stimuli in various brain regions, including the bilateral caudate, temporal gyrus, left frontal gyrus, middle frontal gyrus, and right thalamus. LIMITATIONS: Participants were individuals with polysubstance use; therefore, we were not able to examine the effects of individual substances. CONCLUSIONS: Our findings suggest that HRU displays lower responses to reward stimuli within the left DS and other non-hypothesized brain regions. Our findings may help further elucidate reward processing dysfunctions related to substance misuse.


Assuntos
Pacientes Internados , Transtornos Relacionados ao Uso de Substâncias , Humanos , Encéfalo , Recompensa , Transtornos Relacionados ao Uso de Substâncias/psicologia , Mapeamento Encefálico/métodos
12.
Autophagy ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953310

RESUMO

Co-occurring mutations in KEAP1 in STK11/LKB1-mutant NSCLC activate NFE2L2/NRF2 to compensate for the loss of STK11-AMPK activity during metabolic adaptation. Characterizing the regulatory crosstalk between the STK11-AMPK and KEAP1-NFE2L2 pathways during metabolic stress is crucial for understanding the implications of co-occurring mutations. Here, we found that metabolic stress increased the expression and phosphorylation of SQSTM1/p62, which is essential for the activation of NFE2L2 and AMPK, synergizing antioxidant defense and tumor growth. The SQSTM1-driven dual activation of NFE2L2 and AMPK was achieved by inducing macroautophagic/autophagic degradation of KEAP1 and facilitating the AXIN-STK11-AMPK complex formation on the lysosomal membrane, respectively. In contrast, the STK11-AMPK activity was also required for metabolic stress-induced expression and phosphorylation of SQSTM1, suggesting a double-positive feedback loop between AMPK and SQSTM1. Mechanistically, SQSTM1 expression was increased by the PPP2/PP2A-dependent dephosphorylation of TFEB and TFE3, which was induced by the lysosomal deacidification caused by low glucose metabolism and AMPK-dependent proton reduction. Furthermore, SQSTM1 phosphorylation was increased by MAP3K7/TAK1, which was activated by ROS and pH-dependent secretion of lysosomal Ca2+. Importantly, phosphorylation of SQSTM1 at S24 and S226 was critical for the activation of AMPK and NFE2L2. Notably, the effects caused by metabolic stress were abrogated by the protons provided by lactic acid. Collectively, our data reveal a novel double-positive feedback loop between AMPK and SQSTM1 leading to the dual activation of AMPK and NFE2L2, potentially explaining why co-occurring mutations in STK11 and KEAP1 happen and providing promising therapeutic strategies for lung cancer.

13.
Langmuir ; 29(1): 102-9, 2013 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-23210742

RESUMO

A photoresponsive micellar solution is developed as a promising working fluid for district heating/cooling systems (DHCs). It can be reversibly switched between a drag reduction (DR) mode and an efficient heat transfer (EHT) mode by light irradiation. The DR mode is advantageous during fluid transport, and the EHT mode is favored when the fluid passes through heat exchangers. This smart fluid is an aqueous solution of cationic surfactant oleyl bis(2-hydroxyethyl)methyl ammonium chloride (OHAC, 3.4 mM) and the sodium salt of 4-phenylazo benzoic acid (ACA, 2 mM). Initially, ACA is in a trans configuration and the OHAC/ACA solution is viscoelastic and exhibits DR (of up to 80% relative to pure water). At the same time, this solution is not effective for heat transfer. Upon UV irradiation, trans-ACA is converted to cis-ACA, and in turn, the solution is converted to its EHT mode (i.e., it loses its viscoelasticity and DR) but it now has a heat-transfer capability comparable to that of water. Subsequent irradiation with visible light reverts the fluid to its viscoelastic DR mode. The above property changes are connected to photoinduced changes in the nanostructure of the fluid. In the DR mode, the OHAC/trans-ACA molecules assemble into long threadlike micelles that impart viscoelasticity and DR capability to the fluid. Conversely, in the EHT mode the mixture of OHAC and cis-ACA forms much shorter cylindrical micelles that contribute to negligible viscoelasticity and effective heat transfer. These nanostructural changes are confirmed by cryo-transmission electron microscopy (cryo-TEM), and the photoisomerization of trans-ACA and cis-ACA is verified by (1)H NMR.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34174484

RESUMO

BACKGROUND: Previous neuroimaging studies have investigated reward-processing dysfunction in major depressive disorder and have led to the common finding that major depressive disorder is associated with reduced reward responses within the reward circuit. Yet it is unclear whether such reward-processing dysfunction is specifically associated with the severity of depressive symptoms in major depressive disorder or is associated with common comorbidities. METHODS: We investigated reward-processing differences using a classic juice-delivery functional magnetic resonance imaging experiment to compare psychiatric patients with severe depressive symptoms (DEPs) to both psychiatric control subjects (PCs) and healthy control subjects. In this study, the DEPs (n = 108) were matched to healthy control subjects (n = 62) for demographic characteristics and to the PCs (n = 108) for demographics and comorbid psychiatric diagnoses. An a priori region of interest, the left putamen, was selected using previous studies. An exploratory whole-brain analysis was performed to explore for nonhypothesized regions. RESULTS: Relative to the PCs and healthy control subjects, the DEP group showed smaller responses to reward stimulus in the left putamen. Whole-brain exploratory analysis revealed that DEPs had significantly lower responses to reward stimulus in the bilateral dorsal striatum (putamen and caudate), middle frontal gyrus, left precentral gyrus, and middle cingulate cortex than PCs. CONCLUSIONS: Our findings suggest that DEPs may have a lesser ability to modulate behavior as a function of reward, especially in those individuals who experience the most severe depressive symptoms. In both DEPs and PCs, the severity of depressive symptoms was related to reduced reward responses in the left putamen.


Assuntos
Transtorno Depressivo Maior , Humanos , Depressão , Pacientes Internados , Encéfalo , Recompensa
15.
J Psychiatr Res ; 158: 172-179, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36586216

RESUMO

Over the last several decades, inpatient psychiatric length of stay (LOS) has been greatly reduced to the detriment of patients. Latent variable mixture modeling, can be used to improve the quality of care for patients by identifying unobserved subgroups and optimize treatment variables, including LOS. This study had three objectives (1) to replicate the findings made by Oh et al. in a distinct sample, (2) to examine demographic differences related to inpatient treatment trajectories, and (3) to relate additional variables to each trajectory. We collected data on six key mental illness factors and information on felonies, misdemeanors, history of stopping psychiatric medication and psychotherapy, length of time in psychotherapy, and the number of therapists and psychiatrists from 489 patients at an inpatient psychiatric hospital. We derived latent mental illness scores after applying growth mixture modeling to these data. We identified three distinct trajectories of mental illness change: High-Risk, Rapid Improvement (HR-RI), Low-Risk, Partial Response (LR-PR), and High-Risk, Gradual Improvement (HR-GI). The HR-GI group was more likely to have patients who were female, Asian, younger, Yearly Income (YI) <$20,000, that spent more time in psychotherapy throughout their life, and had the longest LOS while inpatient. The LR-PR group had was more likely to be male, Hispanic/Latino and multiracial, older, YI >$500,000, have a history of misdemeanors, and this group had the shortest LOS (p < .05). These findings replicate and extend our previous findings in Oh et al. (2020a) and highlight the clinical utility of agnostically determining the treatment trajectories.


Assuntos
Transtornos Mentais , Saúde Mental , Humanos , Masculino , Feminino , Transtornos Mentais/terapia , Psicoterapia , Hospitalização , Fatores de Tempo
16.
J Am Chem Soc ; 134(35): 14375-81, 2012 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-22909263

RESUMO

Helical tubules are a fascinating and an intriguing class of self-assemblies. They occur frequently in biology and are believed to be intermediates in formation of gallstones. The pathway by which amphiphiles transform from an initial state of vesicles or micelles into such tubules has puzzled soft matter physicists, and it has raised important questions about the interplay between molecular chirality and self-assembly. Here, for the first time, we demonstrate direct, real-time observations by light microscopy of the pathway to helical microtubules from an initial solution of nanoscale vesicles. The tubules are formed in aqueous mixtures of the single-tailed diacetylenic surfactant, 10,12-pentacosadiynoic acid (PCDA), and a short-chain alcohol. The stepwise process involves nucleation of thin helical microribbons from the vesicle solution. These ribbons then thicken, rearrange, and fold into closed tubules. Subsequently, most tubules further rearrange into plate-like structures, and once again, we are able to visualize this process in real time. A notable aspect of the above system is that the precursors are achiral; yet, the tubules are formed from helical ribbons. Our study provides new insights into tubule formation that will be valuable in clarifying and refining theoretical models for these fascinating structures.


Assuntos
Microscopia , Microtúbulos/química , Microtúbulos/metabolismo , Ácidos Graxos Insaturados/química , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformação Molecular , Tensoativos/química , Fatores de Tempo
17.
Biomacromolecules ; 13(10): 3388-94, 2012 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-22970880

RESUMO

Biopolymers bearing hydrophobic side-chains, such as hydrophobically modified chitosan (hmC), can connect liposomes into a gel network via hydrophobic interactions. In this paper, we show that such liposome gels possess an attractive combination of properties for certain drug delivery applications. Their shear-thinning property allows these gels to be injected at a particular site, while their gel-like nature at rest ensures that the material will remain localized at that site. Moreover, drugs can be encapsulated in the interior of the liposomes and delivered at the local site for an extended period of time. The presence of two transport resistances - from the liposomal bilayer and the gel network - is shown to be responsible for the sustained release; in turn, disruption of the liposomes both weakens the gel and causes a faster release. We have monitored release kinetics from liposome gels of a cationic anticancer drug doxorubicin (Dox) encapsulated in liposomes. Sustained release of Dox from these gels and the concomitant cytotoxic effect could be observed for over a week.


Assuntos
Antineoplásicos/farmacologia , Biopolímeros/farmacologia , Quitosana/farmacologia , Sistemas de Liberação de Medicamentos , Lipossomos/farmacologia , Antineoplásicos/química , Biopolímeros/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Géis/química , Géis/farmacologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipossomos/química , Estrutura Molecular , Reologia , Relação Estrutura-Atividade
18.
J Neuroimaging ; 32(4): 752-764, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35044016

RESUMO

BACKGROUND AND PURPOSE: The effective connectivity of neuronal networks during passive saltatory pneumotactile velocity stimulation to the glabrous hand with different velocities is still unknown. The present study investigated the effectivity connectivity elicited by saltatory pneumotactile velocity arrays placed on the glabrous hand at three velocities (5, 25, and 65 cm/second). METHODS: Dynamic causal modeling (DCM) was used on functional MRI data sampled from 20 neurotypical adults. Five brain regions, including the left primary somatosensory (SI) and motor (M1) cortices, bilateral secondary somatosensory (SII) cortices, and right cerebellar lobule VI, were used to build model space. RESULTS: Three velocities (5, 25, and 65 cm/second) of saltatory pneumotactile stimuli were processed in both serial and parallel modes within the sensorimotor networks. The medium velocity of 25 cm/second modulated forward interhemispheric connection from the contralateral SII to the ipsilateral SII. Pneumotactile stimulation at the medium velocity of 25 cm/second also influenced contralateral M1 through contralateral SI. Finally, the right cerebellar lobule VI was involved in the sensorimotor networks. CONCLUSIONS: Our DCM results suggest the coexistence of both serial and parallel processing for saltatory pneumotactile velocity stimulation. Significant contralateral M1 modulation promotes the prospect that the passive saltatory pneumotactile velocity arrays can be used to design sensorimotor rehabilitation protocols to activate M1. The effective connectivity from the right cerebellar lobule VI to other cortical regions demonstrates the cerebellum's role in the sensorimotor networks through feedforward and feedback neuronal pathways.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Adulto , Encéfalo , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos
19.
RSC Adv ; 12(5): 2589-2594, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35425284

RESUMO

Investigations to evaluate the extreme ultraviolet (EUV) lithographic performance of 160 nm thick poly(methyl methacrylate) with 13.5 nm wavelength EUV light were performed using a synchrotron radiation source at Pohang Light Source-II (PLS-II). The single system enabled the determination of the sensitivity, contrast, linear absorption coefficient, critical dimension, and line edge roughness of polymer thin films through tests and measurements. The experimental findings were also compared to theoretical results and those of previously reported studies. According to the results of the dose-to-clear test and transmission measurements, the critical dimension of a line and space pattern (>50 nm) via interference lithography with 250 nm pitch grating agreed well with the results calculated using the lumped parameter model. The experimental results demonstrated that the equipment and test protocol can be used for EUV material infrastructure evaluation in academia and in industry.

20.
RSC Adv ; 11(3): 1517-1523, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35424089

RESUMO

A highly fluorinated alternating polymer, P(RFMi-St), possessing improved thermal properties and patterning capabilities over perfluoroalkyl polymethacrylates under high energy radiation was achieved with semi-perfluorododecyl maleimide (RFMi) and styrene (St). RFMi could be synthesised efficiently via a Mitsunobu reaction condition and copolymerised with St by free radical and reversible-deactivation radical polymerisation protocols. P(RFMi-St) showed a satisfactory glass-transition temperature (108 °C) and intermolecular cross-linking behaviour under electron-beam and commercially more important extreme UV (λ = 13.5 nm) irradiation. The exposed regions lost their solubility, resulting in the successful formation of mechanically non-deteriorated negative-tone images down to 50 nm. In addition, P(RFMi-St) could be solution-processed with chemically non-damaging fluorous liquids, which enabled the polymer to be applied effectively on top of an organic semiconductor layer as a dielectric material (dielectric constant 2.7) for the organic field-effect transistor fabrication.

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