An improved method to estimate ultrasonic absorption in agar-based gel phantom using thermocouples and MR thermometry.

In this paper, a novel experimental set-up was developed that measures the absorption coefficient. The proposed system was evaluated in an agar-based gel phantom. The new experimental system provides accurate and fast measurement of the rate of temperature change within the phantom. The rate of temperature change was measured using thermocouple and was confirmed using MR thermometry. An ultrasonic transducer with a broad beam was used in order to reduce the conduction effect. The absorption coefficient of the agar-based phantom was 0.26 dB/cm-MHz using 4% agar, 30% evaporated milk and 4% silica. The absorption coefficient increased by increasing the volume of the evaporated milk, and agar. The absorption coefficient increased at low silica concentration (<4%) and then decreased at higher concentration of silica (>4%). By proper selection of evaporated milk, agar and silica concentration, it is possible to achieve similar coefficient like in soft tissues. Acoustic absorption measurement is considered as a difficult measurement in ultrasonics because obtaining the precise temperature change in the focus is challenging. Due to the quick and accurate placement of the thermocouple at the ultrasonic beam, it is possible with the proposed system to perform absorption measurement is less than one minute.

Development and validation of a reversed-phase high-performance liquid chromatographic method for the quantitation and stability of α-lipoic acid in cosmetic creams.

OBJECTIVE: To develop and validate a simple reversed-phase HPLC method for the quantitation and evaluation of stability of α-lipoic acid in cosmetics, according to International Conference on Harmonization (ICH) Guidelines. METHODS: The chromatography was performed on a reversed-phase Luna C18, analytical column (150 × 4.6 mm id, 5 µm particle size) with a mobile phase of potassium dihydrogen phosphate (pΗ 4.5; 0.05 M) and acetonitrile (60:40, v/v) and a flow rate of 1.0 mL min-1 with UV detection at 340 nm. Accelerated and long-term stability studies of α-lipoic acid in cosmetic cream were conducted under various degradation conditions including acid, basis, oxidation, and thermal and photolytic degradation, according to European Medicines Agency Guidelines CPMP/ICH/2736/99. RESULTS: The limit of detection (LOD) for the cosmetic cream was 0.9 µg mL-1 and the limit of quantitation (LOQ) was 2.8 µg mL-1 , while the retention time was 7.2 min. The method proved to be linear, precise and accurate. The stability results demonstrated the selectivity of the proposed method to the analysis of α-LA, and the degradation products were determined and evaluated in specific stress conditions in cosmetic creams. The applicability of the method was tested in two different developed cosmetic products (cream with 1.5 % w/w and emulsion with 1.0 % w/w of LA) and proved to be reliable. CONCLUSION: A reversed-phase HPLC-UV method was developed and fully validated for the analysis of α-lipoic acid in cosmetics. It is the first reported application on the quantitation of lipoic acid in cosmetic creams, while at the same time evaluates the stability in forced degradation conditions, in new cosmetic formulations. It proved to be suitable for the reliable quality control of cosmetic products, with a run time of <8 min that allows for the analysis of large number of samples per day.

OBJECTIF: Développer et valider une méthode HPLC (chromatographie en phase liquide à haute performance) simple en phase inversée pour la quantification et l'évaluation de la stabilité de l'acide α-lipoïque dans les cosmétiques, conformément aux Directives de la Conférence internationale sur l'harmonisation (ICH). MÉTHODE: La chromatographie a été réalisée sur une colonne analytique Luna C18 en phase inversée (150 × 4,6 mm id, taille des particules 5 µm) avec une phase mobile de dihydrogénophosphate de potassium (pH 4,5 ; 0,05 M) et d'acétonitrile (60:40, v/v) et un débit de 1,0 ml min−1 avec détection UV à 340 nm. Des études de stabilité accélérée et à longterme de l'acide α-lipoïque dans les crèmes cosmétiques ont été menées dans diverses conditions de dégradation, notamment en milieu acide, basique, par oxydation et dégradation thermique et photolytique, conformément aux lignes directrices de l'Agence européenne des médicaments CPMP/ICH/2736/99. RÉSULTAT: La limite de détection (LD) pour la crème cosmétique était de 0,9 µg ml et la limite de quantification (LQ) était de 2,8 µml−1 , tandis que le temps de rétention était de 7,2 min. La méthode s'est avérée linéaire, précise et exacte. Les résultats de stabilité ont démontré la sélectivité de la méthode proposée pour l'analyse de l'acide α-lipoïque et les produits de dégradation ont été déterminés et évalués dans des conditions de stress spécifiques dans les crèmes cosmétiques. L'applicabilité de la méthode a été testée dans deux produits cosmétiques différents développés (crème avec 1,5 % p/p et émulsion avec 1,0 % p/p d'acide lipoïque) et s'est avérée fiable. CONCLUSION: une méthode HPLC en phase inversée avec détection UV a été développée et entièrement validée pour l'analyse de l'acide α-lipoïque dans les cosmétiques. Il s'agit de la première application signalée concernant la quantification de l'acide lipoïque dans les crèmes cosmétiques et permettant en même temps d'évaluer la stabilité des conditions de dégradation forcée dans les nouvelles formulations cosmétiques. Cette méthode s'est avérée adaptée au contrôle de qualité fiable des produits cosmétiques, avec une durée d'exécution < 8 min qui permet l'analyse d'un grand nombre d'échantillons par jour.

Understanding of Faux Pas in patients with schizophrenia.

Theory of Mind (ToM) refers to our ability to attribute mental states such as beliefs, intentions and desires to other, allowing us to explain, manipulate and predict others' behavior. ToM abilities of patients with schizophrenia were repeatedly found to be deficient. Our purpose in undertaking the present study was to explore ToM deficits in patients with schizophrenia, using a task of an affective aspect of ToM abilities, namely, "Faux Pas" Test (FPT). The FPT requires a "cognitive" ToM ability (i.e., knowing that the person who insults the other has not realized that she/he should not do that) and a more "affective" component (i.e., empathizing for the person who received the insulting utterance). We assessed 40 inpatients with schizophrenia (32 men) and 30 healthy participants (24 men), matching on age, level of education and sex ratio. All patients met DSM-IV criteria for schizophrenia. Four written scenarios containing a faux pas (unintentionally insulting or hurtful statements given a particular context) were presented to each examinee. The participants read each scenario and responded to a series of 4 questions: "Did anyone say something she/he should not have said?" (faux pas detection); "Why shouldn't she/he have said it?" (appreciation of potential negative impact on others); "Why do you think she/he said it?" (appreciation of speaker's lack of consideration); "How do you think the other person might have felt?" (awareness of other's emotional reaction). Patients with schizophrenia performed more poorly than healthy participants across all conditions: detection of FP [U=366.5, p=0.001], reasons should not have made FP [U=215.5, p<0.001], reasons for making FP [t(65)=4.294, p<0.001], and empathy [U=372, p=0.001]. Only the third condition (reasons for making FP) was significantly correlated with the age at first diagnosis (r=0.462, =0.004) and with ratings of positive symptoms (r=-0.391, p=0.017) and with symptoms of general psychopathology (r=-0.339, p=0.040). The present study further supports previous findings of patients with schizophrenia difficulties in theory of mind, as it was measured through a faux pas which also assess, apart from the understanding of a person' s mental state, the understanding of a person's emotional state, after having received an unintentional insult. The inability of patients with schizophrenia to empathize and therefore detect a faux pas may cause serious problems in their everyday communication with others. Appropriate cognitive interventions may help patients to avoid unintentionally hurting other people's emotions, thus improving their interpersonal relationships.

Controlled shifting of attention in schizophrenia and bipolar disorder through a dichotic listening paradigm.

The dichotic listening (DL) task was developed originally to examine bottom-up or "automatic" information processing. More recently, however, it has been used as a tool in the study of top-down or "controlled" information processing. This has been done by including forced-choice conditions, wherein the examinee is required to focus attention on one or the other ear. It has been widely utilized with patients with schizophrenia, who exhibit rather severe deficits in managing their attention, but not with other patient groups, such as patients with bipolar disorder. In the present study, we examined potential performance similarities in the DL listening task. In total, the sample consisted of 38 patients with schizophrenia, 20 patients with psychotic bipolar disorder and 35 healthy individuals, who performed a DL task with verbal stimuli once at the beginning of their hospitalization and again on the last day before discharge. Our findings indicated that both patient groups showed similarly diminished performance when compared to healthy participants at both times of administration. Symptom improvement between the two evaluations did not significantly influence performance in the DL task. In conclusion, impaired automated and controlled information processing appears to be a common deficit in both schizophrenia and bipolar disorder.

Identification of novel modifiers of Aß toxicity by transcriptomic analysis in the fruitfly.

The strongest risk factor for developing Alzheimer's Disease (AD) is age. Here, we study the relationship between ageing and AD using a systems biology approach that employs a Drosophila (fruitfly) model of AD in which the flies overexpress the human Aß42 peptide. We identified 712 genes that are differentially expressed between control and Aß-expressing flies. We further divided these genes according to how they change over the animal's lifetime and discovered that the AD-related gene expression signature is age-independent. We have identified a number of differentially expressed pathways that are likely to play an important role in the disease, including oxidative stress and innate immunity. In particular, we uncovered two new modifiers of the Aß phenotype, namely Sod3 and PGRP-SC1b.

Semantic priming in remitted patients with bipolar disorder.

BACKGROUND AND OBJECTIVES: Semantic priming disturbances are increasingly recognized as a feature of schizophrenia, and increased priming has been suggested to constitute a "cognitive correlate" of positive formal thought disorder (FTD). The present study aimed to investigate semantic priming in patients with bipolar disorder (BD). METHODS: A primed lexical decision task with strongly related (STR), weakly related (WR), or unrelated (UR) prime-target pairs (SOA = 250 ms) was administered to fourteen remitted patients with BD and twelve control subjects matched on key demographic variables. FTD was measured by means of the Scale for Thought, Language and Communication (TLC). RESULTS: Control subjects showed a robust (59.6 ms) and statistically significant priming effect for STR words, while priming for UR words was non-significant. In patients there was no evidence of priming in either condition. In patients, there were no significant correlations between priming magnitude and TLC scores. However, the only patient with a positive score on the TLC disorganization factor exhibited evidence of hyperpriming. LIMITATIONS: The present patient sample exhibited very low TLC scores, and no direct comparison to patients with schizophrenia was possible. CONCLUSIONS: The finding of decreased priming in patients with BD raises the possibility that semantic processing abnormalities in BD are of a different nature than those encountered in schizophrenia. Due to the small size and very low TLC scores of the present patient sample, no definite conclusions can be drawn as to the relationship of formal thought disorder and semantic processing abnormalities in BD.

Insights into theory of mind in schizophrenia: the impact of cognitive impairment.

The ability to mentalize and attribute beliefs, intentions and desires to others has been found by the vast majority of studies to be impaired in patients with schizophrenia. However, it is not yet clear if this deficit in Theory of Mind (ToM) is independent of their also well established deficits in basic cognitive functioning. In the present study, we sought to clarify the above relationship by exploring patients' ToM impairment after controlling for their putative cognitive deficits. We examined 36 patients with schizophrenia and 30 healthy matched controls on first and second order tasks of ToM and on commonly used neuropsychological tests. Patients performed poorly on ToM tasks even after controlling for their cognitive deficits, particularly on second order ToM. The present findings contribute to the understanding of the mechanism of ToM, suggesting that ToM deficits are core characteristics in schizophrenia and relatively independent of patients' cognitive impairment.

Characterization of the Drosophila melanogaster alkali-metal/proton exchanger (NHE) gene family.

The NHE family of Na+/H+ exchangers is believed to play an essential role in animals, but may play an additional, specialised epithelial role in insects. The pharmacological sensitivity of the Drosophila melanogaster Malpighian tubule to a range of amiloride derivatives was shown to be consistent with an effect on an exchanger, rather than a Na+ channel. Consistent with this, no degenerin/epithelial Na+ channel (ENaC) genes could be detected in Malpighian tubules by reverse transcriptase/polymerase chain reaction (RT-PCR). Using a low-stringency homology searching, three members of the NHE family were identified in the genomic sequence of Drosophila melanogaster, although only two genes were represented as expressed sequence tags. All three genes (DmNHE1 at cytological position 21B1, DmNHE2 at 39B1 and DmNHE3 at 27A1) were found by RT-PCR to be widely expressed, and one (DmNHE2) was shown to have multiple transcripts. The putative translations of the three genes mark them as distantly related members of the family, inviting the possibility that they may serve distinct roles in insects.

GRASP55, a second mammalian GRASP protein involved in the stacking of Golgi cisternae in a cell-free system.

We have identified a 55 kDa protein, named GRASP55 (Golgi reassembly stacking protein of 55 kDa), as a component of the Golgi stacking machinery. GRASP55 is homologous to GRASP65, an N-ethylmaleimide-sensitive membrane protein required for the stacking of Golgi cisternae in a cell-free system. GRASP65 exists in a complex with the vesicle docking protein receptor GM130 to which it binds directly, and the membrane tethering protein p115, which also functions in the stacking of Golgi cisternae. GRASP55 binding to GM130, could not be detected using biochemical methods, although a weak interaction was detected with the yeast two-hybrid system. Cryo-electron microscopy revealed that GRASP65, like GM130, is present on the cis-Golgi, while GRASP55 is on the medial-Golgi. Recombinant GRASP55 and antibodies to the protein block the stacking of Golgi cisternae, which is similar to the observations made for GRASP65. These results demonstrate that GRASP55 and GRASP65 function in the stacking of Golgi cisternae.

Altered patterns of gene expression in Arabidopsis elicited by cauliflower mosaic virus (CaMV) infection and by a CaMV gene VI transgene.

Cauliflower mosaic virus (CaMV) gene VI protein (P6) is an important determinant of symptom expression. Differential display polymerase chain reaction (PCR) was used to identify changes in gene expression in Arabidopsis elicited by a P6 transgene that causes a symptomatic phenotype. We used slot blot hybridization to measure the abundance of mRNAs complementary to 66 candidate PCR products in transgenic, CaMV-infected, and uninfected Arabidopsis plants. CaMV-infected and P6 transgenic plants showed broadly similar changes in abundance of mRNA species. In P6 transgenic plants we detected 18 PCR products that showed unambiguous changes in abundance plus another 15 that showed more limited changes (approximately twofold). CaMV-infected plants showed 17 unambiguous and 13 limited changes. Down-regulated species include those encoding a novel, phenol-like sulfotransferase, and a glycine-rich, RNA-binding protein. Up-regulated species included ones encoding an myb protein, glycine-rich and stress-inducible proteins, and a member of a previously unreported gene family. CaMV infection causes alterations in expression of many Arabidopsis genes. Transgene-mediated expression of P6 mimics virus infection in its effect on host gene expression, providing a potential mechanism for this process.