A Cognitive Constraint on Negative Polarity Phenomena

Proceedings of the Twentieth Annual Meeting of the Berkeley Linguistics Society: General Session Dedicated to the Contributions of Charles J. Fillmore (1994

Perfluorooctane Sulfonate (PFOS) and Related Perfluorinated Compounds in Human Maternal and Cord Blood Samples: Assessment of PFOS Exposure in a Susceptible Population during Pregnancy

Fluorinated organic compounds (FOCs), such as perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorooctane sulfonylamide (PFOSA), are widely used in the manufacture of plastic, electronics, textile, and construction material in the apparel, leather, and upholstery industries. FOCs have been detected in human blood samples. Studies have indicated that FOCs may be detrimental to rodent development possibly by affecting thyroid hormone levels. In the present study, we determined the concentrations of FOCs in maternal and cord blood samples. Pregnant women 17–37 years of age were enrolled as subjects. FOCs in 15 pairs of maternal and cord blood samples were analyzed by liquid chromatography–electrospray mass spectrometry coupled with online extraction. The limits of quantification of PFOS, PFOA, and PFOSA in human plasma or serum were 0.5, 0.5, and 1.0 ng/mL, respectively. The method enables the precise determination of FOCs and can be applied to the detection of FOCs in human blood samples for monitoring human exposure. PFOS concentrations in maternal samples ranged from 4.9 to 17.6 ng/mL, whereas those in fetal samples ranged from 1.6 to 5.3 ng/mL. In contrast, PFOSA was not detected in fetal or maternal samples, whereas PFOA was detected only in maternal samples (range, < 0.5 to 2.3 ng/mL, 4 of 15). Our results revealed a high correlation between PFOS concentrations in maternal and cord blood (r(2) = 0.876). However, we did not find any significant correlations between PFOS concentration in maternal and cord blood samples and age bracket, birth weight, or levels of thyroid-stimulating hormone or free thyroxine. Our study revealed that human fetuses in Japan may be exposed to relatively high levels of FOCs. Further investigation is required to determine the postnatal effects of fetal exposure to FOCs

Assessment of macular choroidal thickness by optical coherence tomography and angiographic changes in central serous chorioretinopathy.

[Objective]: To investigate the relationship between macular choroidal thickness measured by highpenetrating swept-source optical coherence tomography (SS-OCT) and angiographic findings in central serous chorioretinopathy (CSC). [Design]: Prospective cross-sectional case series. [Participants and Controls]: Thirty-four patients with CSC (44 eyes) and 17 volunteer subjects (17 normal eyes). [Methods]: All subjects underwent a comprehensive ophthalmologic and SS-OCT prototype examination. All patients with CSC also underwent simultaneous fluorescein angiography (FA) and indocyanine green angiography (IA). Mean regional choroidal thickness measurements on the Early Treatment Diabetic Retinopathy Study (ETDRS) layout and squared sector grids were obtained by 3-dimensional raster scanning using SS-OCT. [Main Outcome Measures]: Macular choroidal thickness and angiographic abnormalities. [Results]: Mean whole macular choroidal thickness in eyes with CSC (total, 329.3_83.0 _m; classic CSC, 326.9_83.1 _m; chronic CSC, 325.4_93.3 _m; and multifocal posterior pigment epitheliopathy, 359.0_15.5 _m) was greater than that in normal eyes (233.0_67.0_m) (P_ 0.001). In unilateral cases, mean whole macular choroidal thickness was greater in eyes with unilateral CSC than in unaffected fellow eyes (P_0.021). There was no significant difference in choroidal thickness between active eyes and resolved eyes in any of the ETDRS sectors. Mean choroidal thickness was greater in areas with leakage on FA than in areas without leakage (P_0.001). Mean choroidal thickness was greater in areas with choroidal vascular hyperpermeability and in areas with punctate hyperfluorescent spots on IA than in unaffected areas (P_0.001 for both). [Conclusions]: Increased choroidal thickness was observed in the whole macular area of eyes with any of the CSC subtypes. Choroidal thickness was related to leakage from the retinal pigment epithelium, choroidal vascular hyperpermeability, and punctate hyperfluorescent lesions. These findings provide evidence that CSC may be caused by focally increased hydrostatic pressure in the choroid. [Financial Disclosure(s)]: Proprietary or commercial disclosure may be found after the references

Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy

<p>Abstract</p> <p>Background</p> <p>Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year.</p> <p>Methods</p> <p>Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up.</p> <p>Results</p> <p>Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT.</p> <p>Conclusions</p> <p>These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.</p

SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis

Hepatocellular carcinomas (HCCs) mainly develop from liver cirrhosis and severe liver fibrosis that are established with long-lasting inflammation of the liver. Silencing of the suppressor of the cytokine signaling-1 (SOCS1) gene, a negative regulator of cytokine signaling, by DNA methylation has been implicated in development or progress of HCC. However, how SOCS1 contributes to HCC is unknown. We examined SOCS1 gene methylation in >200 patients with chronic liver disease and found that the severity of liver fibrosis is strongly correlated with SOCS1 gene methylation. In murine liver fibrosis models using dimethylnitrosamine, mice with haploinsufficiency of the SOCS1 gene (SOCS1−/+ mice) developed more severe liver fibrosis than did wild-type littermates (SOCS1+/+ mice). Moreover, carcinogen-induced HCC development was also enhanced by heterozygous deletion of the SOCS1 gene. These findings suggest that SOCS1 contributes to protection against hepatic injury and fibrosis, and may also protect against hepatocarcinogenesis

A Role of Aromatase in Sjögren Syndrome

Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is a converting enzyme from androgens to estrogens. In the present study, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 (MCP-1) increased in white adipose tissue (WAT) of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M-1 macrophage was observed in WAT of ArKO mice. A significantly increased MCP-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjögren’s syndrome (SS) were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play in a key role in the pathogenesis of SS-like lesions by controlling the target organ and adipose tissue-associated macrophage

Gene panel analysis of 119 index patients with suspected periodic paralysis in Japan

IntroductionGenetic factors are recognized as the major reason for patients with periodic paralysis. The goal of this study was to determine the genetic causes of periodic paralysis in Japan.MethodsWe obtained a Japanese nationwide case series of 119 index patients (108 men and 11 women) clinically suspected of periodic paralysis, and a gene panel analysis, targeting CACNA1S, SCN4A, and KCNJ2 genes, was conducted.ResultsFrom 34 cases, 25 pathogenic/likely pathogenic/unknown significance variants were detected in CACNA1S (nine cases), SCN4A (19 cases), or KCNJ2 (six cases), generating a molecular diagnostic rate of 28.6%. In total, seven variants have yet been found linked to periodic paralysis previously. The diagnostic yield of patients with hypokalemic and hyperkalemic periodic paralyzes was 26.2 (17/65) and 32.7% (17/52), respectively. A considerably higher yield was procured from patients with than without positive family history (18/25 vs. 16/94), onset age ≤20 years (24/57 vs. 9/59), or recurrent paralytic attacks (31/94 vs. 3/25).DiscussionThe low molecular diagnostic rate and specific genetic proportion of the present study highlight the etiological complexity of patients with periodic paralysis in Japan