Evaluation of Pax6 Mutant Rat as a Model for Autism

Autism is a highly variable brain developmental disorder and has a strong genetic basis. Pax6 is a pivotal player in brain development and maintenance. It is expressed in embryonic and adult neural stem cells, in astrocytes in the entire central nervous system, and in neurons in the olfactory bulb, amygdala, thalamus, and cerebellum, functioning in highly context-dependent manners. We have recently reported that Pax6 heterozygous mutant (rSey2/+) rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI). In the present study, we further examined behaviors of rSey2/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal) in addition to impairment in rearing activity and in fear-conditioned memory. Ultrasonic vocalization (USV) in rSey2+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey2/+ rats likely have some phenotypic components of autism

Defining a standard set of patient-centered outcomes for men with localized prostate cancer

Background Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. Objective To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. Design, setting, and participants We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. Outcome measurements and statistical analysis The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. Results and limitations We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. Conclusions We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. Patient summary Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer

A prospective, multi-method, multi-disciplinary, multi-level, collaborative, social-organisational design for researching health sector accreditation [LP0560737]

BACKGROUND: Accreditation has become ubiquitous across the international health care landscape. Award of full accreditation status in health care is viewed, as it is in other sectors, as a valid indicator of high quality organisational performance. However, few studies have empirically demonstrated this assertion. The value of accreditation, therefore, remains uncertain, and this persists as a central legitimacy problem for accreditation providers, policymakers and researchers. The question arises as to how best to research the validity, impact and value of accreditation processes in health care. Most health care organisations participate in some sort of accreditation process and thus it is not possible to study its merits using a randomised controlled strategy. Further, tools and processes for accreditation and organisational performance are multifaceted. METHODS/DESIGN: To understand the relationship between them a multi-method research approach is required which incorporates both quantitative and qualitative data. The generic nature of accreditation standard development and inspection within different sectors enhances the extent to which the findings of in-depth study of accreditation process in one industry can be generalised to other industries. This paper presents a research design which comprises a prospective, multi-method, multi-level, multi-disciplinary approach to assess the validity, impact and value of accreditation. DISCUSSION: The accreditation program which assesses over 1,000 health services in Australia is used as an exemplar for testing this design. The paper proposes this design as a framework suitable for application to future international research into accreditation. Our aim is to stimulate debate on the role of accreditation and how to research it.Jeffrey Braithwaite, Johanna Westbrook, Marjorie Pawsey, David Greenfield, Justine Naylor, Rick Iedema, Bill Runciman, Sally Redman, Christine Jorm, Maureen Robinson, Sally Nathan and Robert Gibber

Ferromagnetic coupling by orthogonal magnetic orbitals in a heterodinuclear (CuVIV)-V-II=O complex and in a homodinuclear (CuCuII)-Cu-II complex

Glaser T, Theil H, Liratzis I, Weyhermuller T, Bill E. Ferromagnetic coupling by orthogonal magnetic orbitals in a heterodinuclear (CuVIV)-V-II=O complex and in a homodinuclear (CuCuII)-Cu-II complex. INORGANIC CHEMISTRY. 2006;45(13):4889-4891.The heterodinuclear complex [(LCuVIVO)-V-II] 1 was synthesized by using a new unsymmetric dinucleating ligand based on 1,8-naphthalenediol, whereas the homodinuclear (CuCuII)-Cu-II complex 2 has a bridging beta-diketimineamid unit. Here we report on the synthesis, molecular structures, and magnetic properties of 1 and 2. In the solid state, both complexes dimerize to tetranuclear entities 1(2) and 2(2). The intradimer interaction in both complexes is ferromagnetic because of the orthogonality of the magnetic orbitals (J(12) = +45.6 cm(-1) in 1 and +4.8 cm(-1) in 2). The interdimer interaction in 1 is also ferromagnetic, giving a S-t = 2 ground state

The electronic structures of an isostructural series of octahedral nitrosyliron complexes {Fe-NO}(6,7,8) elucidated by Mossbauer spectroscopy

Hauser C, Glaser T, Bill E, Weyhermuller T, Wieghardt K. The electronic structures of an isostructural series of octahedral nitrosyliron complexes {Fe-NO}(6,7,8) elucidated by Mossbauer spectroscopy. Journal of the American Chemical Society. 2000;122(18):4352-4365.From the reaction of cis-[(cyclam)Fe-III(Cl)(2)]Cl (cyclam = 1,4,8,11-tetraazacyclotetradecane) with hydroxylamine in water the octahedral nitrosyliron complexes trans-[(cyclam)Fe(NO)Cl](ClO4) (1) and cis-[(cyclam)Fe(NO)I]I (2) have been isolated as crystalline solids. EPR spectroscopy and variable-temperature susceptibility measurements established that 1 possesses an S = 1/2 and 2 an S = 3/2 ground state; both species are of the (Fe-NO}(7) type. Electrochemically, 1 can be reversibly one-electron oxidized yielding trans-[(cyclam)Fe(NO)Cl](2+), an {Fe-NO}(6) species, and one-electron reduced yielding trans-[(cyclam)Fe(NO)Cl](0), an {FeNO)(8) species. These complexes have been characterized in CH3CN solutions by UV-vis and EPR spectroscopy; both possess a singlet ground state. All of these nitrosyliron complexes, including [LFe(NO)(N-3)(2)] (S = 3/2; L = 1,4,7-trimethyl-1,4,7-triazacyclononane) and [L'Fe(NO)(ONO)(NO2)](ClO4) (S = 0; L' = 1,4,7-triazacyclononane), have been studied by variable-temperature Mossbauer spectroscopy both in zero and applied fields. The oxidation of 1 is best described as metal-centered yielding a complex with an Fe-IV (S = 1) coupled antiferromagnetically to an NO- (S = 1), whereas its reduction is ligand-centered and yields a species with a low-spin ferric ion (S = 1/2) antiferromagnetically coupled to an NO2- (S = 1/2) In agreement with Solomon et al. (J. Am. Chem. Sec. 1995, 117, 715) both {Fe-NO}(7) (S = 3/2) species in this work are described as high-spin ferric (S = 5/2) antiferromagnetically coupled to an NO- (S = 1). Complex 1 is proposed to contain an intermediate spin ferric ion (S = 3/2) antiferromagnetically coupled to NO- (S = 1). The alternative descriptions as low-spin ferric antiferromagnetically coupled to NO- (S 1) or low-spin ferric with an NO(S = 0) ligand are ruled out by the applied field Mossbauer spectra

Sn(III) and Ge(III) in the Thiophenolato-Bridged Complexes [LFeSnFeL]n+\mathrm{[LFeSnFeL]^{n+}} and [LFeGeFeL]n+\mathrm{[LFeGeFeL]^{n+}}( n = 2, 3; L = 1,4,7-(4- tert -Butyl-2-mercaptobenzyl)-1,4,7-triazacyclononane)

The reaction of mononuclear [LFeIII] where L represents the trianionic ligand 1,4,7-tris(4-tert-butyl-2-mercaptobenzyl)-1,4,7-triazacyclononane with Pb(ClO4)2·3H2O in methanol affords the heterotrinuclear complex [LFePbFeL](ClO4)2 (1). Similarly, with SnSO4 or GeI2 as starting material in an acetonitrile/water mixture and CH2Cl2, respectively, the reaction with [LFeIII] yields crystalline materials of [LFeSnFeL](PF6)2 (2a) and [LFeGeFeL](PF6)2 (3a) upon addition of NaPF6. Complexes 2a and 3a can be one-electron oxidized by [NiIII(tacn)2](ClO4)3 (tacn = 1,4,7-triazacyclononane) to give [LFeSnFeL](ClO4)3 (2b) and [LFeGeFeL](ClO4)3 (3b). The crystal structures of [LFeSnFeL](BPh4)2·6CH3CN (2a*), [LFeSnFeL](ClO4)3·4.5(CH3)2CO (2b*), and [LFeGeFeL](BPh4)2·6CH3CN (3a*) have been determined by single-crystal X-ray crystallography. The trinuclear cations consist of three face-sharing octahedra connected by six thiolato bridges affording the core N3Fe(μ-S)3M(μ-S)3FeN3 (M = Sn,Ge). Fe and Sn(Ge) K edge X-ray absorption spectroscopy on 2a, 2b, and 3a, 3b established that the one-electron oxidations affect exclusively the iron ions whereas the oxidation state of the central Sn(Ge) remains unaffected. 119Sn(57Fe) Mössbauer spectroscopy, magnetochemistry, and EPR spectroscopy prove that both the Sn and Ge ions in the di- and trications are trivalent since the unpaired electron in 2b and 3b displays substantial 5s and 4s character, respectively. In contrast, in 1, an oxidation state distribution of l.s.FeIIIPbIIl.s.FeIII prevails. Complexes 1, 2a, and 3a possess a diamagnetic ground state whereas 2b and 3b have an St = 1/2 ground state

Trinuclear Nickel Complexes with Triplesalen Ligands: Simultaneous Occurrence of Mixed Valence and Valence Tautomerism in the Oxidized Species

Glaser T, Heidemeier M, Fröhlich R, Hildebrandt P, Bothe E, Bill E. Trinuclear Nickel Complexes with Triplesalen Ligands: Simultaneous Occurrence of Mixed Valence and Valence Tautomerism in the Oxidized Species. Inorg. Chem. 2005;44(15):5467-5482.The coordination chemistries of the triple tetradentate triplesalen ligands H(6)talen, H(6)talen(t-Bu2), and H(6)talen(NO2) have been investigated with nickel(II). These triplesalen ligands provide three salen-like coordination environments bridged in a meta-phenylene arrangement by a phloroglucinol backbone. The structures of the complexes [(talen)Ni-3(II)], [(talen(t-Bu2))Ni-3(II)], and [(talen(NO2))Ni-3(II)] have been determined by single-crystal X-ray diffraction, All three compounds are composed of neutral trinuclear complexes with square-planar coordinated Ni-II ions in a salen-like coordination environment. Whereas the overall molecular structure of [(talen(NO2))Ni-II3] is nearly planar, the structures of [(talen)Ni-II3] and [(talen(t-Bu2))Ni-3(II)] are bowl-shaped as a result of ligand folding. The strongest ligand folding occurs at the central nickel-phenolate bond of [(talen(t-Bu2))Ni-3(II)], resulting in the formation of a chiral hemispherical pocket, The dependence of the physical properties by the substituents on the terminal phenolates has been studied by FTIR, resonance Raman, UV-vis-NIR absorption, and electrochemistry. The three nickel-salen subunits are electronically interacting via the 7, system of the bridging phloroglucinol backbone. The strength of this interaction is mediated by two opposing effects: the electron density at the terminal phenolates and the folding of the ligand at the central phenolates. The parent complex [(talen)Ni-3(II)] is irreversibly oxidized at 0.32 V versus ferrocenium/ferrocene (Fc(+)/ Fc), whereas [(talen(t-Bu2))Ni-3(II)] and [(talen(NO2))Ni-3(II)] exhibit reversible oxidations at 0.22 V versus Fc(+)/Fc and 0.52 V versus Fc(+)/Fc, respectively. The oxidized species [(talen(t-Bu2))Ni-3](+) and [(talen(NO2))Ni-3](+) undergo a valence-tautomeric transformation involving a Ni-II and a phenoxyl radical species, as observed by EPR spectroscopy. Thus, these oxidized forms exhibit the phenomena of valence tautomerism and mixed valence simultaneously. The extent of delocalization of the radical species and of the Ni-II species is discussed

Structural Influence of Delocalized Electrons Studied by XAS

Meyer-Klaucke W, Glaser T, Bill E, Wieghardt K, Trautwein AX. Structural Influence of Delocalized Electrons Studied by XAS. HASYLAB Jahresbericht. 1996;1996:811-812