186 research outputs found

    The “Lasso Sign”: An Early Sonographic Sign of Posterior Meningocele

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    Posterior meningocele is an uncommon form of spina bifida. We present a case of unique posterior meningocele diagnosed at the early second trimester anatomical scan using 2D and 3D ultrasound. The sonographic appearance resembled “lasso”. The prenatal follow-up was uneventful, with no demonstration of tethered cord. Clinical, neurological and radiological examinations following delivery and at the age of four months were unremarkable

    Differential loss of spinal interneurons in a mouse model of ALS

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    Amyotrophic lateral sclerosis (ALS) leads to a loss of specific motor neuron populations in the spinal cord and cortex. Emerging evidence suggests that interneurons may also be affected, but a detailed characterization of interneuron loss and its potential impacts on motor neuron loss and disease progression is lacking. To examine this issue, the fate of V1 inhibitory neurons during ALS was assessed in the ventral spinal cord using the SODG93A mouse model. The V1 population makes up ∼30% of all ventral inhibitory neurons, ∼50% of direct inhibitory synaptic contacts onto motor neuron cell bodies, and is thought to play a key role in modulating motor output, in part through recurrent and reciprocal inhibitory circuits. We find that approximately half of V1 inhibitory neurons are lost in SODG93A mice at late disease stages, but that this loss is delayed relative to the loss of motor neurons and V2a excitatory neurons. We further identify V1 subpopulations based on transcription factor expression that are differentially susceptible to degeneration in SODG93A mice. At an early disease stage, we show that V1 synaptic contacts with motor neuron cell bodies increase, suggesting an upregulation of inhibition before V1 neurons are lost in substantial numbers. These data support a model in which progressive changes in V1 synaptic contacts early in disease, and in select V1 subpopulations at later stages, represent a compensatory upregulation and then deleterious breakdown of specific interneuron circuits within the spinal cord

    Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer

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    Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (P(SNP-trend)) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (P(Region) and P(Pathway)) were assessed by combining individual P(SNP-trend) values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (P(SNP-FDR)/P(SNP-trend) = 0.02/6×10(−6) and P(SNP-FDR)/P(SNP-trend) = 0.04/2×10(−5), respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0–13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (P(Region-FDR)/P(Region = )0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (P(Pathway) = 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC

    Examining the Dimensionality, Reliability, and Invariance of the Depression, Anxiety, and Stress Scale–21 (DASS-21) Across Eight Countries

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    © The Author(s) 2020. This study evaluated the dimensionality, invariance, and reliability of the Depression, Anxiety, and Stress Scale–21 (DASS-21) within and across Brazil, Canada, Hong Kong, Romania, Taiwan, Turkey, United Arab Emirates, and the United States (N = 2,580) in college student samples. We used confirmatory factor analyses to compare the fit of four different factor structures of the DASS-21: a unidimensional model, a three-correlated-factors model, a higher order model, and a bifactor model. The bifactor model, with three specific factors (depression, anxiety, and stress) and one general factor (general distress), presented the best fit within each country. We also calculated ancillary bifactor indices of model-based dimensionality of the DASS-21 and model-based reliability to further examine the validity of the composite total and subscale scores and the use of unidimensional modeling. Results suggested the DASS-21 can be used as a unidimensional scale. Finally, measurement invariance of the best fitting model was tested across countries indicating configural invariance. The traditional three-correlated-factors model presented scalar invariance across Canada, Hong Kong, Romania, Taiwan, and the United States. Overall, these analyses indicate that the DASS-21 would best be used as a general score of distress rather than three separate factors of depression, anxiety, and stress, in the countries studied

    Cross-Cultural Validation of the Perceptions of Stigmatization by Others for Seeking Help (PSOSH) Scale

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    Social network stigma refers to the perceived negative views about seeking help for mental health problems that are held by those closest to an individual, such as family and friends. This form of stigma predicts help-seeking attitudes and intentions beyond other forms of stigma, and is predominantly measured using the Perceptions of Stigmatization by Others for Seeking Help scale (PSOSH; Vogel, Wade, & Ascheman, 2009). However, the PSOSH was normed using samples from the United States and, until the cross-cultural validity of this measure is established, it cannot reliably be used within other countries (Miller & Sheu, 2008). As such, the current study (N = 3,440) examined the cross-cultural measurement invariance of the PSOSH using the sequential constraint imposition approach across 11 countries/regions: Australia, Brazil, Canada, Hong Kong, Portugal, Romania, Taiwan, Turkey, the United Arab Emirates (UAE), the United Kingdom (U.K.), and the United States (U.S.). Overall, findings indicate that the PSOSH measures a meaningful construct (i.e., configural and metric invariance) across the 11 countries/regions and that future cross-cultural research could use the PSOSH to examine relationships between social network stigma and other variables. Scalar invariance results also supported the examination of mean differences in Australia, Brazil, Canada, Portugal, Turkey, the U.K., and the U.S., but not in Hong Kong, Romania, Taiwan, and UAE. Implications for future cross-cultural research are discussed

    Stigma of Seeking Psychological Services: Examining College Students Across Ten Countries/Regions

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    © Division of Counseling Psychology of the American Psychological Association. Stigma is an important barrier to seeking psychological services worldwide. Two types of stigma exist: public stigma and self-stigma. Scholars have argued that public stigma leads to self-stigma, and then self-stigma is the primary predictor of attitudes toward seeking psychological services. However, this assertion is largely limited to U.S. samples. The goal of this research was to provide a first step in understanding the relationship between public stigma, self-stigma, and attitudes toward seeking psychological services in international contexts (N = 3,276; Australia, Brazil, Canada, Hong Kong, Portugal, Romania, Taiwan, Turkey, United Arab Emirates, and United States). Using structural equation modeling, we found that self-stigma mediated the relationship between public stigma and attitudes toward seeking services among college students in each country and region. However, differences in path strengths emphasize the need to pay attention to the role of public and self-stigma on attitudes toward seeking psychological services throughout the world

    Subclinical Hypothyroidism after Radioiodine Exposure: Ukrainian–American Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident (1998–2000)

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    BackgroundHypothyroidism is the most common thyroid abnormality in patients treated with high doses of iodine-131 (131I). Data on risk of hypothyroidism from low to moderate 131I thyroid doses are limited and inconsistent.ObjectiveThis study was conducted to quantify the risk of hypothyroidism prevalence in relation to 131I doses received because of the Chornobyl accident.MethodsThis is a cross-sectional (1998-2000) screening study of thyroid diseases in a cohort of 11,853 individuals < 18 years of age at the time of the accident, with individual thyroid radioactivity measurements taken within 2 months of the accident. We measured thyroid-stimulating hormone (TSH), free thyroxine, and antibodies to thyroid peroxidase (ATPO) in serum.ResultsMean age at examination of the analysis cohort was 21.6 years (range, 12.2-32.5 years), with 49% females. Mean 131I thyroid dose was 0.79 Gy (range, 0-40.7 Gy). There were 719 cases with hypothyroidism (TSH > 4 mIU/L), including 14 with overt hypothyroidism. We found a significant, small association between (131)I thyroid doses and prevalent hypothyroidism, with the excess odds ratio (EOR) per gray of 0.10 (95% confidence interval, 0.03-0.21). EOR per gray was higher in individuals with ATPO < or = 60 U/mL compared with individuals with ATPO > 60 U/mL (p < 0.001).ConclusionsThis is the first study to find a significant relationship between prevalence of hypothyroidism and individual (131)I thyroid doses due to environmental exposure. The radiation increase in hypothyroidism was small (10% per Gy) and limited largely to subclinical hypothyroidism. Prospective data are needed to evaluate the dynamics of radiation-related hypothyroidism and clarify the role of antithyroid antibodies

    Mutant p53 facilitates somatic cell reprogramming and augments the malignant potential of reprogrammed cells

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    p53 deficiency enhances the efficiency of somatic cell reprogramming to a pluripotent state. As p53 is usually mutated in human tumors and many mutated forms of p53 gain novel activities, we studied the influence of mutant p53 (mut-p53) on somatic cell reprogramming. Our data indicate a novel gain of function (GOF) property for mut-p53, which markedly enhanced the efficiency of the reprogramming process compared with p53 deficiency. Importantly, this novel activity of mut-p53 induced alterations in the characteristics of the reprogrammed cells. Although p53 knockout (KO) cells reprogrammed with only Oct4 and Sox2 maintained their pluripotent capacity in vivo, reprogrammed cells expressing mutant p53 lost this capability and gave rise to malignant tumors. This novel GOF of mut-p53 is not attributed to its effect on proliferation, as both p53 KO and mut-p53 cells displayed similar proliferation rates. In addition, we demonstrate an oncogenic activity of Klf4, as its overexpression in either p53 KO or mut-p53 cells induced aggressive tumors. Overall, our data show that reprogrammed cells with the capacity to differentiate into the three germ layers in vitro can form malignant tumors, suggesting that in genetically unstable cells, such as those in which p53 is mutated, reprogramming may result in the generation of cells with malignant tumor-forming potential
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