tbuckley/cabot-search huggingface dataset:
Outcome of Dysthymic Disorder at 5-Year Follow-Up: The Effect of Familial Psychopathology, Early Adversity, Personality, Comorbidity, and Chronic Stress
Authors: Elizabeth P. Hayden, Daniel N. Klein
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study sought to identify predictors of course and outcome in dysthymic disorder. METHOD: Eighty-six outpatients with early-onset dysthymic disorder (before age 21) participated in a prospective 5-year follow-up study. Family history of psychopathology, early home environment, axis I and II comorbidity, social support, and chronic stress were assessed at baseline. The Longitudinal Interval Follow-up Evaluation and the Hamilton Depression Rating Scale were used in the follow-up assessments conducted at 30 and 60 months. RESULTS: Comorbid anxiety disorder, cluster C and depressive personality features, and chronic stress were associated with a lower rate of recovery from dysthymic disorder, while family history of bipolar disorder was associated with a higher probability of recovery. Family history of dysthymic disorder, poor childhood maternal and paternal relationships, childhood sexual abuse, cluster C features, neuroticism, a history of anxiety and eating disorders, and chronic stress predicted higher levels of depression at follow-up. Multivariate models indicated that almost all domains contributed to the prediction of course and outcome. CONCLUSIONS: The course and outcome of dysthymic disorder is best conceptualized within a multifactorial framework, with family history of psychopathology, early adversity, axis I and II comorbidity, and chronic stress all making important contributions.
Down-Regulation of Vascular Endothelial Cell Growth Factor-C Expression Using Small Interfering RNA Vectors in Mammary Tumors Inhibits Tumor Lymphangiogenesis and Spontaneous Metastasis and Enhances Survival
Authors: Zhengtang Chen, Michelle L. Varney, Matthew W. Backora, Kenneth Cowan, Joyce C. Solheim, James E. Talmadge, Rakesh K. Singh
Journal: Cancer Research (2005)

Abstract Tumor production of vascular endothelial cell growth factor (VEGF)-C is associated with tumor lymphangiogenesis and lymph node metastasis. In this study, we examined the effects of small interfering RNA (siRNA)–mediated inhibition of VEGF-C on murine mammary tumor growth, metastasis, and survival. The mRNA and protein expression of VEGF-C in murine mammary tumor cells stably transfected with a VEGF-C siRNA vector were significantly lower compared with VEGF-C-control vector-transfected cells. Cl66-siVEGFC tumors had lower levels of lymphangiogenesis and lymph node and spontaneous lung metastasis than Cl66-control tumors. However, we did not observe significant differences in primary tumor growth and experimental lung metastasis between mice injected with Cl66-siVEGFC and Cl66-control cells. In addition, mice bearing Cl66-siVEGFC tumors lived significantly longer than mice bearing Cl66-control tumors. Furthermore, our data suggest that inhibition of VEGF-C modulates immune cell infiltration and their function, which might be critical in tumor immunity. In summary, our data show that inhibition of VEGF-C expression using siRNA-mediated gene silencing vectors reduces lymphangiogenesis and lymph node and spontaneous lung metastasis, and enhances survival.
Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D
Authors: A Erhardt
Journal: Gut (2005)

<b>Background an aims:</b> Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated. <b>Patients and methods:</b> HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases. <b>Results:</b> Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% <i>v</i> 26%; p&lt;0.005). Sustained response to IFN was 46% versus 24% (p&lt;0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p&lt;0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (&gt;2×upper limit of normal) as independent positive predictive parameters of IFN response. <b>Conclusions:</b> The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.
Pleural Effusion from Malignancy
Authors: ALAN LEFF
Journal: Annals of Internal Medicine (1978)

Pleural effusion from metastatic malignancy can cause major impairment of respiratory function and eventual death. Although cure is not possible, successful palliative treatment allows months to years of productive life, obviating the need for continuous hospitalization and repeated thoracenteses. Successful palliative treatment requires obliteration of the pleural space. Literature survey indicates that a wide variety of medical agents and surgical methods have been used with variable success. Medical methods include instillation of antineoplastic agents, antimicrobial agents, or colloidal radioisotopes into the pleural space; quinacrine and tetracycline are moderately to highly effective agents, but the toxicity of the former is substantial. Bedside talc poudrage with thoracostomy-tube drainage is a safe and highly effective alternative. Pleurectomy is the definitive method of preventing reaccumulation of pleural fluid that results from metastatic malignancy, even when other methods have failed, but the high morbidity and mortality of the procedures mandate careful patient selection.
Quality of Outpatient Care Provided to Diabetic Patients: A health maintenance organization experience
Authors: Anne L Peters, Antonio P Legorreta, R Clifford Ossorio, Mayer B Davidson
Journal: Diabetes Care (1996)

OBJECTIVE To document the quality of diabetes care provided to patients in a large health maintenance organization (HMO) from 1 January 1993 to 1 January 1994 and compare it to the standards of the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS To meet a Health Plan and Employer Data Information Set (HEDIS) requirement, a major HMO in California identified 14,539 members with diabetes and randomly selected 384 individuals for review. Charts were available on 353 of these patients, and after obtaining the information for the HEDIS review, additional information was extracted from the charts by an outside chart reviewer. This data set was used for an analysis of the quality of diabetic care provided by the participating medical groups to these HMO members during 1 year. Documentation of follow-up and measures of glycemic and lipid control was examined both for absolute values and for the frequency of measurement over the year. These results were compared to the ADA standards of care. RESULTS Although patients averaged 4.5 visits to their primary care physicians (PCPs) over the year, 21% had one or fewer visits per year. Glycated hemoglobin levels were not documented in 56% of patients (ADA recommends two to four measurements per year), and of those with a glycated hemoglobin level measured. 39% had at least one value ≥ 10%. Fasting plasma glucose concentrations were not documented in 65% of patients (four to six per year recommended). Foot exams (which should be performed at each regular visit) were not documented for 94% of patients. Urine protein measurements were not performed in 52% of patients. Additionally, many patients had elevated and untreated lipid abnormalities. CONCLUSIONS In spite of the frequency of PCP visits during the year for many of these patients, diabetes management was inadequate. This lack of adequate preventive care will lead to an increased risk of the development of the acute and chronic complications of diabetes, creating an even greater future burden on the health care system and negative consequences for patients.
Attenuation of the self-renewal of transit-amplifying osteoblast progenitors in the murine bone marrow by 17β-estradiol
Authors: Gina B. Di Gregorio, Matsuo Yamamoto, A. Afshan Ali, Etsuko Abe, Paula Roberson, Stavros C. Manolagas, Robert L. Jilka
Journal: Journal of Clinical Investigation (2001)

In agreement with evidence that estrogens slow the rate of bone remodeling by suppressing the production of both osteoclasts and osteoblasts, loss of estrogens leads to an increase in the number of osteoclast as well as early osteoblast progenitors (CFU-osteoblasts; CFU-OBs) in the murine bone marrow. Here we show that CFU-OBs are early transit-amplifying progenitors, i.e., dividing cells capable of limited self-renewal, and that 17β-estradiol acts in vivo and in vitro to attenuate their self-renewal by approximately 50%. Consistent with a direct receptor–mediated action of estrogens on early mesenchymal cell progenitors, anti–estrogen receptor-α (anti-ERα) Ab’s stain a small number of marrow cells that exhibit characteristics of primitive undifferentiated cells, including a high nucleus/cytoplasm ratio and lack of lineage-specific biochemical markers; the effect of 17β-estradiol on CFU-OB self-renewal is absent in mice lacking ERα. Because both osteoblasts and the stromal/osteoblastic cells that are required for osteoclast development are derived from CFU-OBs, suppression of the self-renewal of this common progenitor may represent a key mechanism of the anti-remodeling effects of estrogens.
Properties of a protein kinase C-activated chloride current in guinea pig ventricular myocytes.
Authors: K B Walsh, K J Long
Journal: Circulation Research (1994)

Cardiac ventricular myocytes from several species, including the guinea pig, possess a cAMP-dependent protein kinase A (PKA)-activated Cl- channel. In the present study, the properties of a protein kinase C (PKC)-activated Cl- current were studied in isolated guinea pig ventricular myocytes using the whole-cell arrangement of the patch-clamp technique. Intracellular dialysis of ventricular cells with PKC resulted in the activation of a large background current that displayed time-independent kinetics. In the presence of 146 mmol/L external Cl- and 71 mmol/L internal Cl-, the reversal potential (Erev) of the background current (-17 +/- 1 mV) was close to that of the Cl- equilibrium potential (-18 mV), and the current versus voltage relation for the current was outward rectifying in shape. When [Cl-]i or [Cl-]o was reduced by substitution of Cl- with aspartic acid, Erev for the background current shifted in a manner expected for a Cl(-)-selective channel. Based on Erev measurements, the permeability sequence for this PKC-activated Cl- channel was determined to be SCN- &gt; I- &gt; Br- congruent to Cl-. The PKC-activated Cl- current was not inhibited by the Cl- channel blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (100 mumol/L) but could be blocked by anthracene-9-carboxylic acid (1 mmol/L). Activation of the current was abolished in the presence of the PKC inhibitor staurosporine (2.5 mumol/L). Under conditions designed to cause a maximal activation of the Cl- channels by PKC, the addition of forskolin (1 mumol/L) to stimulate PKA caused only a slight further increase in the amplitude of the Cl- current. Thus, PKC activates a Cl- channel in guinea pig ventricular cells with properties similar but not identical to the PKA-activated channel.
Fundamental freedoms and the psychology of threat, bargaining, and inequality
Authors: Adam Sparks, Sandeep Mishra, Pat Barclay
Journal: Behavioral and Brain Sciences (2013)

Abstract Van de Vliert's findings may be explained by the psychology of threat and bargaining. Poor people facing extreme threats must cope by surrendering individual freedom in service of shared group needs. Wealthier people are more able to flee from threats and/or resist authoritarianism, so their leaders must concede greater freedom. Incorporating these factors (plus inequality) can sharpen researchers' predictions.
Doctors, Patients, and Nudging in the Clinical Context—Four Views on Nudging and Informed Consent
Authors: Thomas Ploug, Søren Holm
Journal: The American Journal of Bioethics (2015)

In an analysis of recent work on nudging we distinguish three positions on the relationship between nudging founded in libertarian paternalism and the protection of personal autonomy through informed consent. We argue that all three positions fail to provide adequate protection of personal autonomy in the clinical context. Acknowledging that nudging may be beneficial, we suggest a fourth position according to which nudging and informed consent are valuable in different domains of interaction.
Three-Photon Luminescence of Gold Nanorods and Its Applications for High Contrast Tissue and Deep <i>In Vivo </i>Brain Imaging
Authors: Shaowei Wang, Wang Xi, Fuhong Cai, Xinyuan Zhao, Zhengping Xu, Jun Qian, Sailing He
Journal: Theranostics (2014)

Gold nanoparticles can be used as contrast agents for bio-imaging applications.Here we studied multi-photon luminescence (MPL) of gold nanorods (GNRs), under the excitation of femtosecond (fs) lasers.GNRs functionalized with polyethylene glycol (PEG) molecules have high chemical and optical stability, and can be used as multi-photon luminescent nanoprobes for deep in vivo imaging of live animals.We have found that the depth of in vivo imaging is dependent upon the transmission and focal capability of the excitation light interacting with the GNRs.Our study focused on the comparison of MPL from GNRs with two different aspect ratios, as well as their ex vivo and in vivo imaging effects under 760 nm and 1000 nm excitation, respectively.Both of these wavelengths were located at an optically transparent window of biological tissue (700-1000 nm).PEGylated GNRs, which were intravenously injected into mice via the tail vein and accumulated in major organs and tumor tissue, showed high image contrast due to distinct three-photon luminescence (3PL) signals upon irradiation of a 1000 nm fs laser.Concerning in vivo mouse brain imaging, the 3PL imaging depth of GNRs under 1000 nm fs excitation could reach 600 μm, which was approximately 170 μm deeper than the two-photon luminescence (2PL) imaging depth of GNRs with a fs excitation of 760 nm.
Efalizumab in routine use: a clinical experience
Authors: N. Selenko-Gebauer, F. Karlhofer, G. Stingl
Journal: British Journal of Dermatology (2007)

With the advent of biological therapies, continuous long-term control of psoriasis is now becoming a reality. We report our experience with biologics based on the treatment of more than 550 psoriatic patients with such compounds at our special outpatient care center of Bio-Immunotherapy at the Department of Dermatology of the Medical University of Vienna. Approximately 220 of these patients are currently receiving efalizumab. In our hands, efalizumab was generally found to be safe and well tolerated and, after 12 weeks of treatment, resulted in a PASI reduction of 50% or more in approximately two-thirds of patients treated. In most of these 'early' responders, the therapeutic efficacy of efalizumab can be maintained for a prolonged period of time, in certain patients up to 36 months. Flares occurring during long-term therapy were rare and, in most instances, triggered by infections. During such flares, we usually do not discontinue efalizumab therapy, but rather try to combat the infection by appropriate antibiotics and to control the activity of the cutaneous eruption by the addition of topical (corticosteroids) and, when needed, systemic (e.g. methotrexate 15-20 mg week(-1) for 8-10 weeks) medication. In such a situation, it is of utmost importance for the care-taking physician to closely communicate with the affected patients in a scientifically competent fashion and to have an open ear for their concerns. This helps and improves patient compliance and minimizes the need for treatment discontinuation.
Bone Size Normalizes With Age in Children and Adolescents With Type 1 Diabetes
Authors: Susanne Bechtold, Stefanie Putzker, Walter Bonfig, Oliver Fuchs, Isa Dirlenbach, Hans Peter Schwarz
Journal: Diabetes Care (2007)

The aim of this study was to establish whether type 1 diabetes has a long-term effect on bone development in children and adolescents.Bone characteristics and muscle cross-sectional area (CSA) were analyzed cross-sectionally in 41 (19 female and 22 male) patients and were reevaluated after 5.56 +/- 0.4 years using peripheral quantitative computed tomography (pQCT). We hypothesize that bone size and muscle mass normalize with age.At the first evaluation, mean +/- SD age was 9.87 +/- 2.3 years and disease duration was 4.31 +/- 2.9 years. Height was -0.36 +/- 1.9 SD, and BMI was 0.39 +/- 0.9 SD. Parameters of bone size were low in the whole patient group (corrected for patient's height). At reevaluation, age was 15.44 +/- 2.3 years, and patients had a mean height of -0.12 +/- 0.8 SD. BMI SD had increased to 0.57 +/- 1.1. Total and cortical CSA had normalized. Those patients with an increase in total CSA had a significant younger age at disease manifestation and a younger age at initial pQCT measurement. Bone size was well adapted to muscle mass expressed as the ratio of bone mineral content per muscle mass, and a close correlation was shown between the increase in bone size and in muscle CSA (r = 0.46, P = 0.03).Patients with manifestation of type 1 diabetes at an early age had transient impaired bone development. Within the follow-up period, the greatest increase in bone size was found in these patients. In adolescence, all patients had a normal bone size and appropriate adaptation of bone on muscle.
Effect of Dissemination of Evidence in Reducing Injuries from Falls
Authors: Mary E. Tinetti, Dorothy I. Baker, Mary King, Margaret Gottschalk, Terrence E. Murphy, Denise Acampora, Bradley P. Carlin, Linda Leo-Summers, Heather G. Allore
Journal: New England Journal of Medicine (2008)

Falling is a common and morbid condition among elderly persons. Effective strategies to prevent falls have been identified but are underutilized.
Protease-Activated Receptor-1–Mediated DNA Synthesis in Cardiac Fibroblast Is via Epidermal Growth Factor Receptor Transactivation
Authors: Abdelkarim Sabri, Jacob Short, Jianfen Guo, Susan F. Steinberg
Journal: Circulation Research (2002)

Proteases elaborated by inflammatory cells in the heart would be expected to drive cardiac fibroblasts to proliferate, but protease-activated receptor (PAR) function in cardiac fibroblasts has never been considered. This study demonstrates that PAR-1 is the only known PAR family member functionally expressed by cardiac fibroblasts and that PAR-1 activation by thrombin leads to increased DNA synthesis in cardiac fibroblasts. The increase in DNA synthesis induced by PAR-1 substantially exceeds the effects of other G protein-coupled receptor agonists in this cell type. PAR-1 stimulates phosphoinositide hydrolysis and mobilizes intracellular calcium via pertussis toxin (PTX)-sensitive and PTX-insensitive pathways. Activation of PAR-1 leads to an increase in Src, Fyn, and epidermal growth factor receptor (EGFR) phosphorylation, with EGFR receptor transactivation by Src family kinases the major mechanism for PAR-1-dependent activation of extracellular signal-regulated kinase, p38-mitogen-activated protein kinase, and protein kinase B. Activation of PAR-1 also leads to an increase in DNA synthesis. PAR-1 signaling is highly contextual in nature, inasmuch as PAR-1 activates extracellular signal-regulated kinase and only weakly stimulates protein kinase B via a pathway that does not involve EGFR transactivation in cardiomyocytes. PAR-1 responses in cardiac fibroblasts and cardiomyocytes are predicted to contribute importantly to remodeling during cardiac injury and/or inflammation.
Assessment of the voluntary activation of the diaphragm using cervical and cortical magnetic stimulation
Authors: T Similowski, A Duguet, C Straus, V Attali, D Boisteanu, JP Derenne
Journal: European Respiratory Journal (1996)

The twitch occlusion technique is a promising tool for use in accessing central drive to the diaphragm and determining maximal transdiaphragmatic pressure (Pdi) from submaximal efforts. It clinical use is limited by difficulties inherent to bilateral electrical stimulation (BES) of the phrenic nerves. This study was designed to revisit the technique using cervical magnetic stimulation (CMS). In addition, the effects of a voluntary contraction on diaphragm response to magnetic stimulation of the cortex (CxMS) were studied. Seven volunteers aged 23-33 yrs were studied. Pdi was determined at relaxed functional residual capacity (FRC) in response to BES (Pdi,P-ES) and CMS (Pdi,p-CMS), and the effects of an increasing voluntary contraction (Pdi, vol) were assessed, The same procedure was applied to CxMS. Pdi,p-CMS at relaxed FRC was 27.5 +/- 2.2 cmH2O (mean+/-SEM), about 20% higher than Pdi,p-ES, and reported previously. Pd,p-CMS linearly decreased with Pdi, vol, and six out of seven subjects were capable of producing voluntary contractions sufficient to extinguish the twitch. More complex patterns were observed with CxMS. Cervical magnetic stimulation provides diaphragmatic twitch occlusion data very similar to bilateral electrical phrenic stimulation. Magnetic stimulation, be it cervical or cortical, could probably be helpful for the assessment of central and peripheral mechanisms of diaphragmatic dysfunction in the clinical setting.
Snail Promotes CXCR2 LigandDependent Tumor Progression in NonSmall Cell Lung Carcinoma
Authors: Jane Yanagawa, Tonya C. Walser, Li X. Zhu, Longsheng Hong, Michael C. Fishbein, Vei Mah, David Chia, Lee Goodglick, David A. Elashoff, Jie Luo, Clara E. Magyar, Mariam Dohadwala, Jay M. Lee, Maie A. St. John, Robert M. Strieter, Sherven Sharma, Steven M. Dubinett
Journal: Clinical Cancer Research (2009)

As a transcriptional repressor of E-cadherin, Snail has predominantly been associated with epithelial-mesenchymal transition, invasion, and metastasis. However, other important Snail-dependent malignant phenotypes have not been fully explored. Here, we investigate the contributions of Snail to the progression of non-small cell lung cancer (NSCLC).Immunohistochemistry was done to quantify and localize Snail in human lung cancer tissues, and tissue microarray analysis was used to correlate these findings with survival. NSCLC cell lines gene-modified to stably overexpress Snail were evaluated in vivo in two severe combined immunodeficiency murine tumor models. Differential gene expression between Snail-overexpressing and control cell lines was evaluated using gene expression microarray analysis.Snail is upregulated in human NSCLC tissue, and high levels of Snail expression correlate with decreased survival (P < 0.026). In a heterotopic model, mice bearing Snail-overexpressing tumors developed increased primary tumor burden (P = 0.008). In an orthotopic model, mice bearing Snail-overexpressing tumors also showed a trend toward increased metastases. In addition, Snail overexpression led to increased angiogenesis in primary tumors as measured by MECA-32 (P < 0.05) positivity and CXCL8 (P = 0.002) and CXCL5 (P = 0.0003) concentrations in tumor homogenates. Demonstrating the importance of these proangiogenic chemokines, the Snail-mediated increase in tumor burden was abrogated with CXCR2 blockade. Gene expression analysis also revealed Snail-associated differential gene expression with the potential to affect angiogenesis and diverse aspects of lung cancer progression.Snail upregulation plays a role in human NSCLC by promoting tumor progression mediated by CXCR2 ligands.