Childhood neglect predicts disorganization in schizophrenia through grey matter decrease in dorsolateral prefrontal cortex.

OBJECTIVE: Psychosocial trauma during childhood is associated with schizophrenia vulnerability. The pattern of grey matter decrease is similar to brain alterations seen in schizophrenia. Our objective was to explore the links between childhood trauma, brain morphology and schizophrenia symptoms. METHOD: Twenty-one patients with schizophrenia stabilized with atypical antipsychotic monotherapy and 30 healthy control subjects completed the study. Anatomical MRI images were analysed using optimized voxel-based morphometry (VBM). Childhood trauma was assessed with the Childhood Trauma Questionnaire, and symptoms were rated on the Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS) (disorganization, positive and negative symptoms). In the schizophrenia group, we used structural equation modelling in a path analysis. RESULTS: Total grey matter volume was negatively associated with emotional neglect (EN) in patients with schizophrenia. Whole-brain VBM analyses of grey matter in the schizophrenia group revealed a specific inversed association between EN and the right dorsolateral prefrontal cortex (DLPFC). Path analyses identified a well-fitted model in which EN predicted grey matter density in DLPFC, which in turn predicted the disorganization score. CONCLUSION: Our findings suggest that EN during childhood could have an impact on psychopathology in schizophrenia, which would be mediated by developmental effects on brain regions such as the DLPFC.

Efficient broadband 400 nm noncollinear second-harmonic generation of chirped femtosecond laser pulses in BBO and LBO.

We report on 400 nm broadband type I frequency doubling in a noncollinear geometry with pulse-front-tilted and chirped femtosecond pulses (λ =800 nm; Fourier transform limited pulse duration, 45 fs). With moderate power densities (2 to 10 GW/cm2) thus avoiding higher-order nonlinear phenomena, the energy conversion efficiency was up to 65%. Second-harmonic pulses of Fourier transform limited pulse duration shorter than the fundamental wave were generated, exhibiting good beam quality and no pulse-front tilt. High energy (20 mJ/pulse) was produced in a 40 mm diameter and 6 mm thick LBO crystal. To the best of our knowledge, this is the first demonstration of this optical configuration with sub-100-fs pulses. Good agreement between experimental results and simulations is obtained.

Complete analog control of the carrier-envelope-phase of a high-power laser amplifier.

In this work we demonstrate the development of a complete analog feedback loop for the control of the carrier-envelope phase (CEP) of a high-average power (20 W) laser operating at 10 kHz repetition rate. The proposed method combines a detection scheme working on a single-shot basis at the full-repetition-rate of the laser system with a fast actuator based either on an acousto-optic or on an electro-optic crystal. The feedback loop is used to correct the CEP fluctuations introduced by the amplification process demonstrating a CEP residual noise of 320 mrad measured on a single-shot basis. The comparison with a feedback loop operating at a lower sampling rate indicates an improvement up to 45% in the residual noise. The measurement of the CEP drift for different integration times clearly evidences the importance of the single-shot characterization of the residual CEP drift. The demonstrated scheme could be efficiently applied for systems approaching the 100 kHz repetition rate regime.

Carrier-Envelope Phase stabilization of a 20 W, grating based, chirped-pulse amplified laser, using electro-optic effect in a LiNbO3 crystal.

Using an original CEP stabilization technique based on the linear electro-optical effect in a specific crystal, we achieved long term CEP stabilization of a 20 W, 1 kHz laser with residual noise as low as 440 mrad (rms). At 3 W, the CEP shot to shot noise is kept as low as 320 mrad (rms) over half an hour.

Carrier-envelope phase control using linear electro-optic effect.

We present a new method to control the Carrier-Envelope Phase of ultra-short laser pulses by using the linear Electro-Optic Effect. Experimental demonstration is carried out on a Chirped Pulse Amplification based laser. Phase shifts greater than π radian can be obtained by applying moderate voltage on a LiNbO3 crystal with practically no changes to all other parameters of the pulse with the exception of its group delay. Time response of the Electro-Optic effect makes possible shaping at a high repetition rate or stabilization of the CEP of ultra short CPA laser systems.

[Accidental genital myiasis by Eristalis tenax]. / Miasis genital accidental por Eristalis tenax.

Myiasis is a parasitic infestation of human or animal skin, necrotic tissues and natural cavities by fly larvae or pupa. In this paper we will describe the case of a 27 years old woman, asymptomatic, that spontaneously eliminated from her vagina two Eristalis tenax larvae, a worldwide distributed fly specie, classified as an accidental myiasis agent. The patient lived in an urban area, she had low socioeconomic status and she had the antecedent record of use of intravaginal vegetables as sexual stimulator. Analyzing the case and the references, we concluded the patient had an accidental infestation by E. tenax, being the vaginal introduction of vegetables the most probable mechanism of transmission. This kind of infestation has not been communicated in the literature. Also, this is the first documented case of E. tenax myiasis in Chile.

Miasis genital accidental por Eristalis tenax / Accidental genital myiasis by Eristalis tenax

Myiasis is a parasitic infestation of human or animal skin, necrotic tissues and natural cavities by fly larvae or pupa. In this paper we will describe the case of a 27 years oíd woman, asymptomatic, that spontaneously eliminated from her vagina two Eristalis tenax larvae, a worldwide distributed fly specie, classified as an accidental myiasis agent. The patient lived in an urban área, she had low socioeconomic status and she had the antecedent record of use of intravaginal vegetables as sexual stimulator. Analyzing the case and the references, we concluded the patient had an accidental infestation by E. tenax, being the vaginal introduction of vegetables the most probable mechanism of transmission. This kind of infestation has not been communicated in the literature. Also, this is the first documented case of E. tenax myiasis in Chile.

Las miasis son infestaciones parasitarias de humanos o animales por larvas de mosca que infestan piel, tejidos necróticos y cavidades naturales. Presentamos el caso de una mujer de 27 años, asintomática, que eliminó espontáneamente por vía vaginal larvas de Eristalis tenax, una especie de mosca ampliamente distribuida en el mundo, la que es clasificada como agente de miasis accidental. La paciente residía en un área urbana de nivel socioeconómico bajo y entregaba como antecedente el uso de vegetales intravaginales como estimulante sexual. Analizando el caso descrito y la bibliografía existente, concluimos que la paciente presentó una infestación accidental por E. tenax, siendo el mecanismo más probable de transmisión la introducción vaginal de vegetales. Este mecanismo no ha sido comunicado previamente en la literatura. Además, este es el primer caso de miasis por E. tenax documentado en Chile.

Adaptation and validation of the rheumatoid arthritis quality of life scale for use in Canada.

OBJECTIVE: The Rheumatoid Arthritis Quality of Life questionnaire (RAQoL) was developed simultaneously in the UK and the Netherlands to measure quality of life in patients with RA. We adapted and validated the RAQoL for the English-Canadian and French-Canadian languages and culture. METHODS: The UK RAQoL was translated into French-Canadian by a bilingual translation panel. Separate lay panels were then used to ensure that this and the English-Canadian instruments were appropriate for use with Canadian patients. Interviews were conducted with 15 French-Canadian and 15 English-Canadian patients with RA to determine the content validity. Reliability and construct validity were established by means of test-retest mail surveys conducted with 92 French-Canadian and 87 English-Canadian RA patients. The survey consisted of the adapted RAQoL, the Health Assessment Questionnaire (HAQ), and a demographic questionnaire. RESULTS: The RAQoL was successfully adapted for both the French and English-Canadian cultures. Field testing showed both versions to be well received by respondents. Of the French-Canadian patients included in the postal survey, 52 responded at Time 1 and 50 at Time 2. For the English-Canadian sample, 54 responded at both time points. Missing data rates for the RAQoL were low and floor and ceiling effects were minimal. Test-retest reliability was good for both versions: 0.87 for the French-Canadian and 0.95 for the English-Canadian. Alpha coefficients (0.92 for the French-Canadian, 0.93 for the English-Canadian) showed the items to be adequately interrelated and scores on the measure showed moderate to high correlations with the HAQ, confirming construct validity. Both versions of the RAQoL were also able to distinguish patient groups that differed according to perceived health status and perceived severity of RA. In addition, the French-Canadian version was able to distinguish patients who rated today as bad or very bad from those who rated today as good or very good. CONCLUSION: The new versions of the RAQoL were well received by both French and English speaking Canadians. The psychometric quality of the adapted questionnaires means they are suitable for inclusion in clinical trials involving patients with RA.

Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study.

PURPOSE AND METHODS: We investigated whether a high-dose chemotherapy regimen of cyclophosphamide 1,800 mg/m2, 4'-epidoxorubicin 60 mg/m2, etoposide 330 mg/m2, and cisplatin 120 mg/m2 given monthly for four cycles with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) support (5 micrograms/kg daily for 10 days) could improve the survival of patients with extensive-stage small-cell lung cancer (SCLC) compared with a standard-dose regimen (cyclophosphamide 1,200 mg/m2, 4'-epidoxorubicin 40 mg/m2, etoposide 225 mg/m2, and cisplatin 100 mg/m2) given monthly for six cycles. Planned cumulative doses of the drugs were the same in both treatment arms except for cisplatin (which was 80% in the higher-dose plus rhGM-CSF group). RESULTS: At the time of the preplanned interim analysis, 125 patients, 60 in the standard-dose group and 65 in the higher-dose plus rhGM-CSF group, had entered the study; 116 were eligible, 55 in the standard-dose group and 61 in the higher-dose group. All patients were included in the analyses. The cumulative doses of each drug actually delivered were significantly higher in the standard-dose group. No difference in response rates was observed between the two groups. There were significantly greater hematologic toxicities, documented infections, and transfusions of RBCs and platelets in the higher-dose plus rhGM-CSF group. Patients in this group proved to have a shorter survival duration and a shorter time to relapse than patients in the standard-dose group (median overall survival: standard-dose, 10.8 months; higher-dose, 8.9 months; log-rank test with adjustment for prognostic variables, P = .0005; respective probabilities of relapse at 1 year, 77 +/- 0.6 and 96 +/- 2.2; log-rank test, P = .013). CONCLUSION: A 50% increase in dose-intensity for this four-drug regimen could not be achieved with GM-CSF due to excessive toxicity in patients with extensive-stage SCLC.

Distribution pattern of three neural calcium-binding proteins (NCS-1, VILIP and recoverin) in chicken, bovine and rat retina.

Neural Ca(2+)-binding proteins (NCaPs) constitute a subfamily of 4-EF-hand proteins, and display a histological and structural dichotomy: the A-type NCaPs are selectively expressed by the retina and pineal organ and display two canonical EF-hands, whereas the B-type NCaPs are found in the entire brain and present three regular EF-hands. In this study, antisera were raised against the A-type NCaP recoverin (26 kDa) and the B-type NCaPs VILIP and NCS-1 (22 kDa). Since the sequence identity among NCaPs is high, specific polyclonal antibodies were purified by double cross-immunoaffinity chromatography; both ELISA and immunoblot analyses determined that the resulting antibodies showed selectivity ratios inferior to 1/363 for the two other related NCaPs. Besides, the anti-VILIP antibodies displayed some affinity toward neurocalcin delta, and the antirecoverin antibodies recognized a 24 kDa protein, which is most likely visinin. Thus, immunohistochemical studies on the chicken, rat and cow retina revealed that anti-recoverin antibodies recognized the vertebrate photoreceptors and a small number of mammalian bipolar cells. Anti-VILIP antibodies exclusively labelled the inner retina, i.e. the amacrine and ganglion cells. NCS-1 was mainly present in the photoreceptor inner segments, the inner plexiform layer and the ganglion cells. NCS-1 showed the highest species disparity. The retinal localization of NCS-1 and VILIP offered an important morphological basis for the understanding of their function. Furthermore, specific antibodies against the NCaPs may enable the identification of cell populations in more complex neural tissues, such as the brain.

Thermodynamic and molecular properties of the interaction between amphioxus calcium vector protein and its 26 kDa target.

Calcium vector protein (CaVP) of amphioxus shares some common structural features with Ca(2+)-dependent activators such as troponin C and calmodulin, and is associated in vivo with a 26 kDa (CaVPT), a multidomain protein with one IQ- and two IgII-motifs. Isolated CaVP binds two Ca2+ ions with very different intrinsic affinity constants: K'Ca1 = 4.9 x 10(6) M-1 and K'Ca2 = 7.3 x 10(3) M-1, respectively. In the complex with CaVPT, CaVP also binds two Ca2+, but with strong positive cooperativity (nH = 1.9) and with distinctly higher affinity: K'Ca1 = 2.4 x 10(5) M-1 and K'Ca2 = 1.0 x 10(8) M-1. Since neither in the isolated CaVP nor in the complex Ca2+ binding is influenced by 2 mM MgCl2, both sites can be considered as Ca(2+)-specific. In the absence of Ca2+, the complex is stable under physiological conditions, but the interaction is governed by the principle of linked functions and Ca2+ binding to CaVP reinforces the affinity between CaVP and CaVPT 70-fold. Both proteins interact with the hydrophobic probe 2 p-toluidinylnaphthalene-6-sulfonate (TNS), but CaVPT enhances the fluorescence 45-fold, CaVP-Ca2 and metal-free CaVP only 10- and 5-fold, respectively. Complex formation between CaVPT and CaVP leads to a 3-fold reduction of the fluorescence enhancement, suggesting that a strong solvent-shielded hydrophobic core is formed. CaVP contains two highly reactional thiols (kSH > 0.3 s-1) for 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB); CaVPT contains three thiols, two of them also with kSH > 0.3 s-1 in the native state.(ABSTRACT TRUNCATED AT 250 WORDS)

Cation binding and conformational changes in VILIP and NCS-1, two neuron-specific calcium-binding proteins.

VILIP and NCS-1, neural-specific, 22-kDa Ca(2+)-binding proteins possessing four EF-hands, were expressed in Escherichia coli to study their divalent cation properties. Flow dialysis (Ca2+ binding) and equilibrium gel filtration (Mg2+ binding) revealed that both recombinant proteins possess only two active metal-binding sites, which can accommodate either Ca2+ or Mg2+. VILIP binds cations without cooperativity with intrinsic affinity constants K'Ca of 1.0 x 10(6) M-1 and K'Mg of 4.8 x 10(3) M-1.Mg2+ antagonizes Ca2+ binding by shifting the isotherms to higher free Ca2+ concentrations without changing their shape. The competition equation yields a K'Mg, comp value of 180 M-1 for both sites. NCS-1 binds two Mg2+ without cooperativity with K'Mg of 8.3 x 10(4) M-1 and two Ca2+ with very strong positive cooperativity (nH = 1.96). In the absence of Mg2+ the K'Ca1 and K'Ca2 values are 8.9 x 10(4) and 1.4 x 10(8) M-1, respectively, which represent an allosteric increase of 1600-fold. Mg2+ shifts the Ca(2+)-binding isotherms to higher Ca2+ concentrations, yielding a K'Mg, comp value of 800 M-1 for both sites. Thus VILIP and NCS-1 show three remarkable differences in the Ca2+/Mg2+ binding parameters: 1) VILIP binds Ca2+ with much lower affinity than NCS-1; 2) VILIP binds Ca2+ in a noncooperative way, whereas NCS-1 shows maximal positive cooperativity; 3) in VILIP the Mg2+/Ca2+ antagonism is much weaker than in NCS-1. Conformational changes monitored by Trp fluorescence indicate that the metal-free forms already are highly structured. Ca2+ binding promotes a 20-30% increase of fluorescence in both proteins, but whereas the Mg2+ form of VILIP has the same fluorescence properties as the metal-free form, Mg(2+)-saturated NCS-1 has those of the Ca2+ form. Near UV difference spectra confirmed that in VILIP the Mg2+ form is very similar to the metal-free form; in NCS-1 it is different, especially in the Tyr region. NCS-1 possesses one unique Cys-38 in EF-hand site I. Its reactivity (kSH) toward 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) is the same for the Ca(2+)- and Mg(2+)-loaded protein, but kSH is 4-fold higher in metal-free NCS-1. VILIP possesses two additional thiols, one of which is inaccessible to DTNB in the native protein. The reactivity of the two accessible thiols is identical in the metal-free and Mg2+ forms and 5-fold higher than in the Ca2+ form.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization and primary structure of amphioxus troponin C.

Troponin C (TnC) from amphioxus (Protochordate) was purified and its primary structure determined. Unlike the case of vertebrates and other invertebrates, amphioxus TnC is found in the soluble fraction after extractions at physiological ionic strength in the presence of Ca2+. Edman sequencing combined with mass spectroscopy indicate that the protein contains 163 amino acid residues. It possesses an acetylated N-terminus (although a small percentage has a free Ser N-terminus) and either epsilon-N-methyllysine or epsilon-N-dimethyllysine in position 20. It displays about 50% sequence identity with vertebrate skeletal-muscle and cardiac-muscle TnC, 44% with TnC of sea squirt, also a Protochordate, and 30% with other invertebrate TnC. Like vertebrate TnC, amphioxus TnC contains a N-terminal alpha-helix plus the usual four ancestral Ca(2+)-binding regions, but analysis of the sequence suggests that the fourth site is not functional. Flow dialysis shows that amphioxus TnC binds three Ca2+ with the mean apparent affinity constant K' of 3.4 +/- 1.5 10(5) M-1. No cooperativity exists between the sites, and the presence of up to 10 mM Mg2+ does not influence the Ca(2+)-binding isotherm, indicating that the metal-binding sites are Ca(2+)-specific at physiological Mg2+ concentrations. It forms a Ca(2+)-dependent, 1:1 complex with melittin and rabbit or crayfish troponin I (TnI). Amphioxus TnC possesses one Trp residue in position 151 and one at the C-terminus. Trp fluorescence suggests that one or both residues are solvent-exposed in the metal-free form and efficiently shielded in the Ca2+ form. Although Mg2+ has no effect on the Ca2+ binding, the Trp fluorescence is influenced by millimolar Mg2+, suggesting the presence of one or more independent Mg(2+)-binding site(s). A phylogenetic analysis clearly shows that amphioxus TnC is positioned on the branch of the Chordates, but at a distance from the vertebrate TnC. Its place on the phylogenetic tree is in accordance with the consensus evolutionary phylogeny.

Immunolocalization of calcium vector protein and its target protein in amphioxus.

Three proteins, sarcoplasmic Ca(2+)-binding protein (SCP), Ca2+ vector protein (CaVP) and its target protein (CaVPT), are found abundantly in the higher invertebrate amphioxus. Whereas the function of SCP is likely to be related to Ca2+ and Mg2+ buffering, that of the latter two proteins, apparently linked together, is still not clear. In this study, affinity-purified polyclonal antibodies to these three proteins were used to study the extractability under physiological ionic conditions, the distribution in different tissues and the immunocytochemical localization in striated muscle. Our data show that SCP is essentially cytosolic whereas CaVP and CaVPT are partially associated with non-soluble components in amphioxus tissues. The tissue distribution, studied in transverse sections, shows that SCP is merely confined to striated muscle, whereas CaVP and CaVPT are also abundant in other tissues such as the spinal chord and the gonads. Thus the protein pair CaVP/CaVPT is likely to serve a general role in many tissues; however, no strict correlation was found in the distribution of the latter two proteins, suggesting that they may function independently. The detailed cytochemical localization of the three proteins in longitudinal sections of striated muscle revealed a discrete striation pattern in addition to a diffuse background. For SCP these striations are coincident with the Z line. The immunostaining for CaVP shows intense striations at the level of the Z lines alternating with weak striations at the M lines. For CaVPT the striations at the Z and M line are more or less of equal intensity, leading to a pattern with a 1 micron periodicity.(ABSTRACT TRUNCATED AT 250 WORDS)