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1.
Chemistry ; 28(44): e202200926, 2022 Aug 04.
Article in English | MEDLINE | ID: mdl-35642131

ABSTRACT

The electronic structure and associated spectroscopic properties of ligand-bridged, bimetallic 'mixed-valence' complexes of the general form {M}(µ-B){M+ } are dictated by the electronic couplings, and hence orbital overlaps, between the metal centers mediated by the bridge. In the case of complexes such as [{Cp*(dppe)Ru}(µ-C≡CC6 H4 C≡C){Ru(dppe)Cp*}]+ , the low barrier to rotation of the half-sandwich metal fragments and the arylene bridge around the acetylene moieties results in population of many energy minima across the conformational energy landscape. Since orbital overlap is also sensitive to the particular mutual orientations of the metal fragment(s) and arylene bridge through a Karplus-like relationship, the different members of the population range exemplify electronic structures ranging from strongly localized (weakly coupled Robin-Day Class II) to completely delocalized (Robin-Day Class III). Here, we use electronic structure calculations with the hybrid density functional BLYP35-D3 and a continuum solvent model in combination with UV-vis-NIR and IR spectroelectrochemical studies to show that the conformational population in complexes [{Cp*(dppe)Ru}(µ-C≡CArC≡C){Ru(dppe)Cp*]+ , and hence the dominant electronic structure, can be biased through the steric and electronic properties of the diethynylarylene (Ar) moiety (Ar=1,4-C6 H4 , 1,4-C6 F4 , 1,4-C6 H2 -2,5-Me2 , 1,4-C6 H2 -2,5-(CF3 )2 , 1,4-C6 H2 -2,5-i Pr2 ).

2.
Article in English | WPRIM (Western Pacific) | ID: wpr-886251

ABSTRACT

@#PURPOSE: With continuous positive airway pressure (CPAP) being the treatment of choice for Obstructive Sleep Apnea (OSA), adherence rates to CPAP are still low without a clear consensus of causes. The Self-Determination Theory (SDT) is a general theory of human motivation that emphasizes the extent to which behaviors are relatively autonomous based on the psychological needs that are critical to supporting the process of internalization and the development of optimal motivation. This study sought to determine whether the implementation of an SDT-based intervention is effective in improving: (1) perceived competence, (2) treatment self-regulation, (3) CPAP treatment adherence, and (4) Apnea–hypopnea index (AHI) of OSA patients. METHODS. Using a true experimental pretest-posttest design, 30 purposively selected participants were randomly allocated to experimental and control groups. The SDT-based intervention included group sessions, individual sessions, and follow up phone calls in three weeks. Written permission to conduct the study was obtained from the Institutional Review Board of the University of the East - Ramon Magsaysay Memorial Medical Center, Inc. (UERMMMCI) and the Lung Center of the Philippines. Participation was voluntary and all participants had the right to refuse or discontinue their participation at any time during the study. Data were analyzed using two way repeated-measures ANOVA, student's T-test, and chi-square. RESULTS AND CONCLUSION: The participants in the experimental group have increased adherence rates from Time 1 (60%) to Time 2 (92.9%) and Time 3 (85.7%). Although, when compared to the control group, no significant difference was noted across the different periods of measurement (p=0.70810, p=0870, p=0.2403). There were higher proportions of patients who eventually became adherent in the experimental group compared to the control group immediately after and 5 weeks after the intervention (p=0.0001). The experimental group had significantly better improvement in AHI compared to the control group immediately after (p=0.0152) and 5 weeks after the intervention (p=0.0022). Considering the importance of CPAP adherence in effectively treating OSA, measures to improve adherence such as SDT-based intervention could be usefully incorporated into OSA patients' treatment plans.


Subject(s)
Continuous Positive Airway Pressure , Personal Autonomy , Sleep Apnea, Obstructive
3.
Chemistry ; 25(37): 8837-8853, 2019 Jul 02.
Article in English | MEDLINE | ID: mdl-31050060

ABSTRACT

Class II mixed-valence bimetallic complexes {[Cp'(PP)M]C≡C-C≡N[M'(PP)'Cp']}2+ (M, M'=Ru, Fe; PP=dppe, (PPh3 )2 ; Cp'=Cp*, Cp) exist as conformational ensembles in fluid solution, with a population of structures ranging from cis- to trans-like geometries. Each conformer gives rise to its own series of low-energy intervalence charge-transfer (IVCT) and local d-d transitions, which overlap in the NIR region, giving complex band envelopes in the NIR absorption spectrum, which prevent any meaningful attempt at analysis of the band shape. However, DFT and time-dependent (TD)DFT calculations with dispersion-corrected global-hybrid (BLYP35-D3) or local hybrid (lh-SsirPW92-D3) functionals on a small number of optimised structures chosen to sample the ground state potential energy hypersurfaces of each of these complexes has proven sufficient to explain the major features of the electronic spectra. Although modest in terms of computational expense, this approach provides a more accurate description of the underlying molecular electronic structure than would be possible through analysis of the IVCT band by using the static point-charge model of Marcus-Hush theory and derivatives, or TDDFT calculations from a single (global) minimum energy geometry.

4.
Dalton Trans ; 46(17): 5522-5531, 2017 May 02.
Article in English | MEDLINE | ID: mdl-28054684

ABSTRACT

The cross-conjugated ethynyl-vinylidene [Ph2C[double bond, length as m-dash]C(C[triple bond, length as m-dash]CH){C(H)[double bond, length as m-dash]CRu(PPh3)2Cp}]PF6 ([4a]PF6), and [FcC(H)[double bond, length as m-dash]C(C[triple bond, length as m-dash]CH){C(H)[double bond, length as m-dash]CRu(PPh3)2Cp}]PF6 ([4b]PF6), and ethynyl-alkynyl Ph2C[double bond, length as m-dash]C(C[triple bond, length as m-dash]CH){C[triple bond, length as m-dash]CRu(PPh3)2Cp} (5a), and FcC(H)[double bond, length as m-dash]C(C[triple bond, length as m-dash]CH){C[triple bond, length as m-dash]CRu(PPh3)2Cp} (5b) compounds (Cp = η5-cyclopentadienyl) have been prepared from reactions of the known 3-methylene-penta-1,4-diynes Ph2C[double bond, length as m-dash]C(C[triple bond, length as m-dash]CH)2 (3a) and [FcCH[double bond, length as m-dash]C(C[triple bond, length as m-dash]CH)2] (3b) with [RuCl(PPh3)2Cp]. The compounds derived from 3b incorporating the more electron-rich alkene proved to be unstable during work-up, and attempts to prepare bis(ruthenium) complexes from 3a and 3b or from transmetallation reactions of the bis(alkynylgold) complex FcCH[double bond, length as m-dash]C(C[triple bond, length as m-dash]CAuPPh3)2 (7) with RuCl(PPh3)2Cp were unsuccessful. The related bis- and tris(ferrocenyl) derivatives Ph2C[double bond, length as m-dash]C(C[triple bond, length as m-dash]CFc)2 (6a) and FcCH[double bond, length as m-dash]C(C[triple bond, length as m-dash]CFc)2 (6b) were more readily obtained from Pd(ii)/Cu(i) catalysed cross-coupling reactions of FcC[triple bond, length as m-dash]CH with the 1,1-dibromo vinyl complexes PhC[double bond, length as m-dash]CBr2 (1a) and FcC(H)[double bond, length as m-dash]CBr2 (1b). Cyclic voltammetry of 6a and 6b using n-Bu4N[PF6] as the supporting electrolyte shows broad, overlapping waves arising from the sequential oxidation of the ferrocenyl moieties in electronically and chemically similar environments. Electrostatic effects between the ferrocenyl moieties are enhanced in solutions of the weakly ion-pairing electrolyte n-Bu4N[B{C6H3(CF3)2-3,5}4], leading to better resolution of the individual electrochemical processes. The comparative IR spectroelectrochemical response of 6a and 6b suggest the vinyl ferrocene moiety in 6b undergoes oxidation before the ethynyl ferrocene fragments. There is no evidence of electronic coupling between the metallocene moieties and [6a]+, [6b]n+ (n = 1, 2) are best described as Class I mixed-valence compounds.

5.
Chemistry ; 22(45): 16138-16146, 2016 Nov 02.
Article in English | MEDLINE | ID: mdl-27699904

ABSTRACT

The electronic characteristics of mixed-valence complexes are often inferred from the shape of the inter-valence charge transfer (IVCT) band, which usually falls in the near infrared (NIR) region, and relationships derived from Marcus-Hush theory. These analyses typically assume one single, dominant molecular conformation. The NIR spectra of the prototypical delocalised (Class III Robin-Day mixed-valence) complexes [{Ru(pp)Cp'}2 (µ-C≡C-C≡C)]+ ([1]+ : Cp'=Cp, pp=(PPh3 )2 ; [2]+ : Cp'=Cp, pp=dppe; [3]+ : Cp'=Cp*, pp=dppe) feature a 'two-band' pattern, which complicates band-shape analysis using these traditional methods. In the past, the appearance of sub-bands within or near the IVCT transition has been attributed to vibronic effects or localised d-d transitions. Quantum-chemical modelling of a series of rotational conformers of [1]+ -[3]+ reveals the two components that contribute to the NIR absorption band envelope to be a π-π* transition and an MLCT transition. The MLCT components only gain appreciable intensity when the orientation of the half-sandwich ruthenium ligand spheres deviates from idealised cis (Ω P-Ru-Ru-P=0°) or trans (Ω P-Ru-Ru-P=180°) conformations. The increased steric demand of the supporting ligands, together with some underlying inter-phosphine ligand T-shaped CH⋅⋅⋅π stacking interactions across the series [1]+ to [2]+ to [3]+ results in local minima biased towards such non-idealised conformations of the metal-ligand fragments (Ω P-Ru-Ru-P=33-153°). Experimentally, this is indicated by appearance of multiple bands within the IR ν˜ (C≡C) band envelopes and increasing intensity of the higher-energy MLCT transition(s) relative to the π-π* transition across the series, and the appearance of a pronounced 'two-band' pattern in the experimental NIR absorption envelopes. These conformational effects and the methods of analysis presented here, which combine analysis of IR and NIR spectra with quantum-chemical calculations on a range of energetically similar conformational minima, are expected to be quite general for mixed-valence systems.

6.
J Org Chem ; 80(22): 11501-12, 2015 Nov 20.
Article in English | MEDLINE | ID: mdl-26496049

ABSTRACT

A series of cross-conjugated compounds based on an (E)-4,4'-(hexa-3-en-1,5-diyne-3,4-diyl)bis(N,N-bis(4-methoxyphenyl)aniline) skeleton (1-6) have been synthesized. The linear optical absorption properties can be tuned by modification of the substituents at the 1 and 5 positions of the hexa-3-en-1,5-diynyl backbone (1: Si(CH(CH3)2)3, 2: C6H4C≡CSi(CH3)3, 3: C6H4COOCH3, 4: C6H4CF3, 5: C6H4C≡N, 6: C6H4C≡CC5H4N), although attempts to introduce electron-donating (C6H4CH3, C6H4OCH3, C6H4Si(CH3)3) substituents at these positions were hampered by the ensuing decreased stability of the compounds. Spectroelectrochemical investigations of selected examples, supported by DFT-based computational studies, have shown that one- and two-electron oxidation of the 1,2-bis(triarylamine)ethene fragment also results in electronic changes to the perpendicular π-system in the hexa-3-en-1,5-diynyl branch of the molecule. These properties suggest that (E)-hexa-3-en-1,5-diynyl-based compounds could have applications in molecular sensing and molecular electronics.

7.
J Am Chem Soc ; 137(45): 14319-28, 2015 Nov 18.
Article in English | MEDLINE | ID: mdl-26488257

ABSTRACT

Electrochemical gating at the single molecule level of viologen molecular bridges in ionic liquids is examined. Contrary to previous data recorded in aqueous electrolytes, a clear and sharp peak in the single molecule conductance versus electrochemical potential data is obtained in ionic liquids. These data are rationalized in terms of a two-step electrochemical model for charge transport across the redox bridge. In this model the gate coupling in the ionic liquid is found to be fully effective with a modeled gate coupling parameter, ξ, of unity. This compares to a much lower gate coupling parameter of 0.2 for the equivalent aqueous gating system. This study shows that ionic liquids are far more effective media for gating the conductance of single molecules than either solid-state three-terminal platforms created using nanolithography, or aqueous media.

8.
PeerJ ; 3: e986, 2015.
Article in English | MEDLINE | ID: mdl-26082871

ABSTRACT

A new parvicursorine alvarezsauroid theropod specimen IVPP V20341 from the Upper Cretaceous Wulansuhai Formation of Bayan Mandahu, Inner Mongolia, China is described. IVPP V20341 appears to be distinguishable amongst alvarezsauroids by possible cervical procoely and relatively larger semi-circular caudal neural canals, but these features are not proposed as autapomorphies because current knowledge of alvarezsauroid necks and tails remains sparse. IVPP V20341 is distinguishable from Linhenykus-the sole parvicursorine at Bayan Mandahu-by the location of the origination points of the anterior caudal transverse processes; in IVPP V20341 this is the anterodorsal corner of the centra, whereas in Linhenykus it is the posterior end of the prezygapophyses. A number of additional tentative differences between IVPP V20341 and Linhenykus are also identified, but cannot be confirmed until further details of anatomical variation along the neck and tail are revealed by future finds. Thus, following the study of IVPP V20341 there are still seven parvicursorine species from the Upper Cretaceous Gobi Basin, but future finds could increase this to eight species.

9.
Chemistry ; 20(23): 6895-908, 2014 Jun 02.
Article in English | MEDLINE | ID: mdl-24740610

ABSTRACT

The conformational energy landscape and the associated electronic structure and spectroscopic properties (UV/Vis/near-infrared (NIR) and IR) of three formally d(5)/d(6) mixed-valence diruthenium complex cations, [{Ru(dppe)Cp*}2(µ-C≡CC6H4C≡C)](+), [1](+), [trans-{RuCl(dppe)2}2(µ-C≡CC6H4C≡C)](+), [2](+), and the Creutz-Taube ion, [{Ru(NH3)5}2(µ-pz)](5+), [3](5+) (Cp = cyclopentadienyl; dppe = 1,2-bis(diphenylphosphino)ethane; pz = pyrazine), have been studied using a nonstandard hybrid density functional BLYP35 with 35 % exact exchange and continuum solvent models. For the closely related monocations [1](+) and [2](+), the calculations indicated that the lowest-energy conformers exhibited delocalized electronic structures (or class III mixed-valence character). However, these minima alone explained neither the presence of shoulder(s) in the NIR absorption envelope nor the presence of features in the observed vibrational spectra characteristic of both delocalized and valence-trapped electronic structures. A series of computational models have been used to demonstrate that the mutual conformation of the metal fragments--and even more importantly the orientation of the bridging ligand relative to those metal centers--influences the electronic coupling sufficiently to afford valence-trapped conformations, which are of sufficiently low energy to be thermally populated. Areas in the conformational phase space with variable degrees of symmetry breaking of structures and spin-density distributions are shown to be responsible for the characteristic spectroscopic features of these two complexes. The Creutz-Taube ion [3](5+) also exhibits low-lying valence-trapped conformational areas, but the electronic transitions that characterize these conformations with valence-localized electronic structures have low intensities and do not influence the observed spectroscopic characteristics to any notable extent.


Subject(s)
Coordination Complexes/chemistry , Ruthenium/chemistry , Cations/chemistry , Molecular Conformation , Quantum Theory , Spectrophotometry, Ultraviolet , Spectroscopy, Near-Infrared
10.
Dalton Trans ; 43(17): 6291-4, 2014 May 07.
Article in English | MEDLINE | ID: mdl-24626612

ABSTRACT

The reaction of Fe(C≡CC≡N)(dppe)Cp (1) with one-half equivalent of [trans-Fe(N≡CMe)2(dppx)2][BF4]2 (dppx = dppe ([2][BF4]2) or dppm ([3][BF4]2)) affords trimetallic [trans-Fe{N≡CC≡CFe(dppe)Cp}2(dppx)2][BF4]2 (dppx = dppe [4][BF4]2; dppx = dppm [5][BF4]2). Both [4][BF4]2 and [5][BF4]2 undergo three, one-electron oxidation processes, arising from sequential oxidation of the two terminal Fe(C≡CR)(dppe)Cp moieties and finally the central Fe(N≡CR)2(dppx)2 fragment. The redox products [4](n+) and [5](n+) (n = 3, 4) have been characterised by UV-vis-NIR and IR spectroelectrochemistry. The shifts in the characteristic ν(C≡CC≡N) bands upon oxidation demonstrate not only the localised electronic structure of the trications, but also the redox non-innocence of the cyanoacetylide ligands. The trimetallic [formally Fe(II/II/III) mixed-valence] complexes [4](3+) and [5](3+) feature two distinct IVCT transitions, one associated with charge transfer from the central 18-electron {Fe(N≡CR)2(dppx)2}(2+) to terminal {Fe(C≡CR)(dppe)Cp}(+) moiety, and a lower energy transition involving charge transfer between the terminal Fe fragments which are separated by the redox active 9-atom, 10-bond -C≡C-C≡N{Fe(dppx)2}N≡C-C≡C- bridge. The tetracationic complexes [4](4+) and [5](4+) generated by a further stepwise oxidation exhibit a single {Fe(N≡CR)2(dppx)2}(2+)→{Fe(C≡CR)(dppe)Cp}(+) IVCT transition.

11.
Chemistry ; 19(30): 9780-4, 2013 Jul 22.
Article in English | MEDLINE | ID: mdl-23852956

ABSTRACT

Spinning to improve (band) shape: A blend of theoretical and experimental work demonstrates that the rotational conformation of mixed-valence complexes influences the low-energy (NIR) transitions in such molecules. Interpretations of the NIR band shapes are presented.

12.
Behav Brain Res ; 245: 88-95, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23428746

ABSTRACT

c-Jun N-terminal kinases (JNKs) are central and ubiquitous mediators of cellular signaling for both physiogical-regenerative and pathological-apoptotic processes. Their impact on degeneration or inflammation is well documented, but so far little is known about their roles in higher brain functions. The more, the contribution of individual JNK isoforms remains obscure so far. Here we have tested the behaviour of JNK1, JNK2 and JNK3 knockout (ko) mice in elevated plus maze (EPM), open field (OF), novel object recognition memory (NORM) test and Morris water maze (MWM). Compared with wild type C57BL/6N mice JNK ko mice revealed significant differences. Taken together the data on anxiety, exploration and learning indicate that JNK1 ko mice displayed a stronger explorative behaviour and that knockout of JNK2 or JNK3 showed a tendency of behaviour opposite to that of JNK1 ko mice. This pattern reminds of the impact of individual JNK ko on neurodegeneration. This is the first comparative study on the impact of individual JNK ko on behavioural parameters.


Subject(s)
Behavior, Animal/physiology , Mitogen-Activated Protein Kinase 10/genetics , Mitogen-Activated Protein Kinase 10/physiology , Mitogen-Activated Protein Kinase 8/genetics , Mitogen-Activated Protein Kinase 8/physiology , Mitogen-Activated Protein Kinase 9/genetics , Mitogen-Activated Protein Kinase 9/physiology , Animals , Anxiety/psychology , Blotting, Western , Body Weight/physiology , Brain/enzymology , Exploratory Behavior/physiology , Male , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Motor Activity/physiology , Recognition, Psychology/physiology
13.
Org Biomol Chem ; 10(34): 6914-29, 2012 Sep 14.
Article in English | MEDLINE | ID: mdl-22814352

ABSTRACT

Silicon chemistry offers the potential to tune the effects of biologically active organic molecules. Subtle changes in the molecular backbone caused by the exchange of a carbon atom for a silicon atom (sila-substitution) can significantly alter the biological properties. In this study, the biological effects of a two-fold sila-substitution in the synthetic retinoids EC23 (4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylethynyl)benzoic acid (4a)) and TTNN (6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-2-naphthoic acid (7a)) as well as their corresponding analogues with an indane instead of a 1,2,3,4-tetrahydronaphthalene skeleton (compounds 5a and 8a) were investigated. Two-fold C/Si exchange in 4a, 5a, 7a and 8a leads to the silicon-analogues disila-EC23 (4b), 5b, disila-TTNN (7b) and 8b, which contain a 1,2,3,4-tetrahydro-1,4-disilanaphthalene (4b, 7b) or 1,3-disilaindane skeleton (5b, 8b). Exchange of the SiCH(2)Si moiety of 5b for an SiOSi fragment leads to the disiloxane 6 (2-oxa-1,3-disilaindane skeleton). The EC23 derivative 5a, the TTNN derivative 8a and the silicon-containing analogues 4b, 5b, 6, 7b and 8b were synthesised, and the biological properties of the C/Si pairs 4a/4b, 5a/5b, 7a/7b and 8a/8b and compound 6 were evaluated in vivo using RAR isotype-selective reporter cells. EC23 (4a) and its derivatives disila-EC23 (4b), 5a, 5b and 6 are very potent RAR agonists, which are even more potent than the powerful reference compound TTNPB. Disila-substitution of EC23 (4a) and 5a leads to a moderate decrease in RARα activation, whereas the RARß,γ activation is almost not affected. In contrast, two-fold C/Si exchange in the weak retinoid agonist TTNN (7a) and 8a resulted in considerably different effects: a significant increase (7a→7b) and almost no change (8a→8b) in transcription activation potential for all three RAR isotypes. Disila-TTNN (7b) can be regarded as a powerful RARß,γ-selective retinoid.


Subject(s)
Benzoates/chemical synthesis , Benzoates/pharmacology , Carboxylic Acids/chemical synthesis , Carboxylic Acids/pharmacology , Naphthalenes/chemical synthesis , Naphthalenes/pharmacology , Organosilicon Compounds/chemical synthesis , Organosilicon Compounds/pharmacology , Retinoids/chemical synthesis , Retinoids/pharmacology , Silicon/chemistry , Tetrahydronaphthalenes/chemical synthesis , Tetrahydronaphthalenes/pharmacology , Benzoates/chemistry , Carboxylic Acids/chemistry , Chemistry Techniques, Synthetic , HeLa Cells , Humans , Models, Molecular , Molecular Conformation , Naphthalenes/chemistry , Organosilicon Compounds/chemistry , Retinoids/chemistry , Tetrahydronaphthalenes/chemistry , Transcriptional Activation/drug effects
14.
Am J Geriatr Psychiatry ; 20(9): 782-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-21997601

ABSTRACT

OBJECTIVE: Recent evidence suggests that the sleep-dependent consolidation of declarative memory relies on the nonrapid eye movement rather than the rapid eye movement phase of sleep. In addition, it is known that aging is accompanied by changes in sleep and memory processes. Hence, the purpose of this study was to investigate the overnight consolidation of declarative memory in healthy elderly women. SETTING: Sleep laboratory of University. PARTICIPANTS: Nineteen healthy elderly women (age range: 61-74 years). MEASUREMENTS: We used laboratory-based measures of sleep. To test declarative memory, the Rey-Osterrieth Complex Figure Test was performed. RESULTS: Declarative memory performance in elderly women was associated with Stage 2 sleep spindle density. Women characterized by high memory performance exhibited significantly higher numbers of sleep spindles and higher spindle density compared with women with generally low memory performance. CONCLUSION: The data strongly support theories suggesting a link between sleep spindle activity and declarative memory consolidation.


Subject(s)
Brain Waves/physiology , Memory/physiology , Sleep Stages/physiology , Age Factors , Aged , Female , Humans , Middle Aged , Neuropsychological Tests/statistics & numerical data , Polysomnography/methods , Polysomnography/psychology
15.
Nat Methods ; 8(4): 315-7, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21378979

ABSTRACT

Pluripotent stem cells (PSCs) are defined by their potential to generate all cell types of an organism. The standard assay for pluripotency of mouse PSCs is cell transmission through the germline, but for human PSCs researchers depend on indirect methods such as differentiation into teratomas in immunodeficient mice. Here we report PluriTest, a robust open-access bioinformatic assay of pluripotency in human cells based on their gene expression profiles.


Subject(s)
Computational Biology/methods , Gene Expression Profiling , Pluripotent Stem Cells/physiology , Cell Differentiation , Cell Line , Gene Expression Regulation , Humans , Models, Genetic , Neurons , Oligonucleotide Array Sequence Analysis , Software
16.
BMC Psychiatry ; 10: 91, 2010 Nov 10.
Article in English | MEDLINE | ID: mdl-21067598

ABSTRACT

BACKGROUND: Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia. METHODS: For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected. RESULTS: The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail. CONCLUSIONS: The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.


Subject(s)
Data Collection/methods , Phenotype , Schizophrenia/genetics , Adolescent , Adult , Aged , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Basal Ganglia Diseases/chemically induced , Basal Ganglia Diseases/diagnosis , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Cross-Sectional Studies , Databases, Genetic/statistics & numerical data , Female , Genetic Association Studies , Humans , Male , Middle Aged , Neuropsychological Tests , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Schizophrenic Psychology
17.
J Bone Joint Surg Am ; 92(3): 567-74, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20194314

ABSTRACT

BACKGROUND: Despite an increased risk of cervical spine fractures in older patients, little is known about the mortality associated with these fractures and there is no consensus on the optimal treatment. The purposes of this study were to determine the three-month and one-year mortality associated with cervical spine fractures in patients sixty-five years of age or older and to evaluate potential factors that may influence mortality. METHODS: We performed a retrospective review of all cervical spine fractures in patients sixty-five years of age or older from 1991 to 2006 at two institutions. Information regarding age, sex, race, treatment type, neurological involvement, injury mechanism, comorbidity, and mortality were collected. Overall risk of mortality and mortality stratified by the above factors were calculated at three months and one year. Cox proportional-hazard regression was performed to identify independent correlates of mortality. RESULTS: Six hundred and forty patients were included in our analysis. The mean age was eighty years (range, sixty-five to 101 years). Two hundred and ninety-four patients (46%) were male, and 116 (18%) were nonwhite. The risk of mortality was 19% at three months and 28% at one year. The effect of treatment on mortality varied with age at three months (p for interaction = 0.03) but not at one year (p for interaction = 0.08), with operative treatment being associated with less mortality for those between the ages of sixty-five and seventy-four years. A higher Charlson comorbidity score, male sex, and neurological involvement were all associated with increased risk of mortality. CONCLUSIONS: Operative treatment of cervical spine fractures is associated with a lower mortality rate at three months but not at one year postoperatively for patients between sixty-five and seventy-four years old at the time of fracture.


Subject(s)
Cervical Vertebrae/injuries , Spinal Fractures/mortality , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Massachusetts/epidemiology , Proportional Hazards Models , Radiography , Registries , Retrospective Studies , Risk , Spinal Fractures/diagnostic imaging , Spinal Fractures/therapy
18.
J Trauma ; 68(1): 103-8, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20065764

ABSTRACT

BACKGROUND: Controversy continues as to the most safe and reliable method for clearing the cervical spine (C-spine) in a trauma patient who is rendered unable to participate in a clinical examination. Although magnetic resonance imaging (MRI) is the most sensitive test to detect soft-tissue injuries, it is impractical for routine use in every patient largely because of its cost and time of acquiescence. Recent studies have advocated the sole use of multidetector computed tomographic (MDCT) scans of the C-spine to decide if cervical collar immobilization can be discontinued. The current investigation retrospectively reviewed a series of MDCT scans obtained after an acute traumatic event that were used to direct treatment in the emergency department (ED) or intensive care unit. METHODS: Seven-hundred and eight trauma patients consecutively admitted to the ED between June 2001 and July 2006 underwent a computed tomographic scan of their C-spine as part of an institutional protocol. We identified 91 patients with MDCT scans that were officially recorded as adequate and negative by an attending ED radiologist who had also undergone an MRI during the same trauma admission period. Retrospectively, two fellowship-trained spine surgeons independently reviewed these MDCT studies to address the following questions: (1) Is the study adequate? (2) Is it suggestive of an acute injury? (3) Is there sufficient information to safely recommend collar removal? Institutional Review Board approval was obtained before the images were reviewed. Neither clinical examination findings nor MRI readings were made available to the surgeon evaluators. RESULTS: Both spine surgeons agreed that 76 of the 91 studies (84%) were adequate to evaluate for possible C-spine injuries. Seven of 91 MDCT scans (8%) were deemed inadequate by both surgeons (95% confidence interval, 2.3-13.1). Reasons for inadequacy included motion artifact, insufficient visualization of the cervical-thoracic or occipital-cervical junctions, incomplete reconstructive views, or poor quality. Three of the adequate MDCT scans had fractures that were identified by both of the spine surgeons; 4 additional fractures and 15 findings suspicious for instability were identified by at least one of the surgeons. Ultimately, 22 of 91 MDCT scans read as adequate and normal by attending radiologists were deemed suspicious for abnormality by the spine surgeons. Of these 22 cases, the official MRI reading was positive for a trauma-related abnormality in 17 cases. CONCLUSIONS: C-spine clearance of patients without the ability participate in a clinical examination remains difficult. A multidisciplinary, algorithmic approach generally yields the most consistent results. However, our data highlight that reliance on a single imaging modality may lead to missed diagnosis of C-spine injuries. These data suggest that early involvement of the spine service for radiographic clearance may help identify occult injuries or suspicious findings necessitating further evaluation.


Subject(s)
Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/injuries , Device Removal , Orthotic Devices , Tomography, X-Ray Computed , Humans , Immobilization , Observer Variation , Orthopedics , Spinal Fractures/diagnostic imaging , Spinal Fractures/therapy
19.
J Psychiatr Res ; 44(1): 42-7, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19559446

ABSTRACT

Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Straight memory deficits and sleep disturbances are well-known in patients with schizophrenia. This study tested the hypothesis that patients with schizophrenia have a deficit in procedural and declarative memory consolidation after a short midday nap when compared to healthy controls and patients with remitted to moderate major depression. Following a normal night's sleep, 22 healthy subjects, 20 patients with major depression and 21 patients with schizophrenia were studied in a napping and wake condition in a random-order cross-over design, early in the afternoon. To test declarative memory, the Rey-Osterrieth Complex Figure Test respectively the Taylor Complex Figure Test and, for procedural learning, a mirror tracing task were performed. The present study is the first to demonstrate significant differences between individuals with schizophrenia, depression and healthy matched controls with regard to measures of sleep and memory performance after a short period of daytime sleep (napping). In particular we found that a daytime nap of only about 40min led to improvement of declarative memory performance in all investigated groups, whereas no beneficial effect was seen on procedural performance in the group of medicated patients with schizophrenia in contrast to healthy controls and patients with remitted to moderate major depression.


Subject(s)
Memory Disorders/etiology , Schizophrenia/complications , Sleep Wake Disorders/etiology , Adult , Analysis of Variance , Electromyography/methods , Female , Humans , Male , Neuropsychological Tests , Polysomnography , Retrospective Studies , Wakefulness/physiology , Young Adult
20.
Psychother Psychosom ; 78(3): 187-92, 2009.
Article in English | MEDLINE | ID: mdl-19321972

ABSTRACT

BACKGROUND: The cyclic adenosine monophosphate response element-binding proteins (CREB) and their interaction with brain-derived neurotrophic factor (BDNF) are essential elements in signal transduction pathways important for cellular resilience and neuroplasticity. They play a decisive role in the concept of altered neuroplasticity in major depression. We have previously demonstrated that the increase in phosphorylated CREB (pCREB) in T lymphocytes is significantly associated with clinical improvement in patients treated with antidepressants. In the present study, we focused on patients treated only with psychotherapy to exclude direct pharmacological actions. In addition to pCREB, we also measured the BDNF plasma levels. METHODS: pCREB in T lymphocytes was determined by Western blot; the BDNF plasma levels with solid-phase ELISA. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Thirty patients meeting DSM-IV criteria for major depressive episodes (MDE) were recruited into this 6-week study. They received interpersonal psychotherapy (IPT) twice weekly. RESULTS: After 6 weeks of IPT, 17 patients responded (reduction of > or =50% of baseline HAMD); after 1 week of treatment pCREB increased significantly compared to the nonresponder group. Measurement of the BDNF plasma levels revealed no differences between the responder and nonresponder groups. Furthermore, the correlations between BDNF plasma levels and pCREB were not significant. CONCLUSIONS: The early increase in pCREB is related to treatment response and does not depend on pharmacological interventions or BDNF plasma levels. For the first time, cellular biological markers could be associated with response to psychotherapy.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , CREB-Binding Protein/metabolism , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/therapy , Phosphorylation , Psychotherapy , Blotting, Western , Depressive Disorder, Major/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interpersonal Relations , Male , Neuronal Plasticity , Severity of Illness Index , Signal Transduction , Surveys and Questionnaires , T-Lymphocytes/metabolism
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