tbuckley/cabot-search huggingface dataset:
Depression in Diabetes: Have We Been Missing Something Important?
Authors: Jeffrey S. Gonzalez, Lawrence Fisher, William H. Polonsky
Journal: Diabetes Care (2010)

An extensive literature has developed to suggest that depression is more common in patients with diabetes than in the general population (1) and is associated with chronic hyperglycemia (2), risk for diabetes complications (3), and mortality (4). Although the causal linkages among these relationships have not been demonstrated, their consistency has led to calls for intensive efforts to identify and treat clinical depression in patients with diabetes, with the reasonable presumption that this will contribute to better diabetes outcomes. Recent studies, however, suggest a more complicated picture and cast doubt on this presumption.

Although research has suggested that the prevalence of clinical depression, or major depressive disorder (MDD), among adults with diabetes may be two to three times greater than among community adults (1), recent studies—which have used structured clinical interviews, the gold standard in the diagnosis of MDD—suggest that it is only about 60% more common (5). More importantly, diabetes-related distress, or significant negative emotional reactions to the diagnosis of diabetes, threat of complications, self-management demands, unresponsive providers, and/or unsupportive interpersonal relationships, has been found to be far more common, more chronic, and more closely related to diabetes self-care and glycemic control than MDD (5–7).

Symptoms of depression, such as depressed mood, diminished interest, loss of energy, and concentration difficulties, that are elevated but do not meet severity criteria for MDD (referred to here as depressive symptoms) are also quite common among patients with diabetes and are associated with poor self-care (8). Furthermore, increased risk of complications and early mortality is not limited to those with MDD but also extends to those with elevated depressive symptoms, even when these elevations are quite modest (4). This suggests an incremental relationship between the severity of depressive symptoms and poorer diabetes outcomes rather than an effect of MDD per …
Sleep apnoea and cancer: current insights and future perspectives
Authors: Miguel Ángel Martínez-García, Francisco Campos-Rodríguez, Ramon Farré
Journal: European Respiratory Journal (2012)

It seems paradoxical to observe how obstructive sleep apnoea (OSA) has been associated with a large number of systemic diseases, and is even recognized as a risk factor for some of them [1–4], but is nevertheless, strictly speaking, basically a local mechanical problem resulting from intermittent collapses of the upper airway during sleep. The explanation for this phenomenon is that these repetitive airway obstructions trigger several pathophysiological mechanisms that have an overall systemic effect. Thus, sympathetic activation, periodical hypoxaemias–normoxaemias, hypercapnia, arousals and changes in intrathoracic pressure induced by OSA lead to the activation of some pathophysiological pathways similar to those observed in several cardiovascular diseases [5]. This explains why OSA has been associated with the onset, poor control and worsened prognosis of some of the most prevalent cardiovascular diseases, such as arterial hypertension [6], cardiac arrhythmias [7], and cerebral and cardiovascular events [3, 4]. One aspect that has been far less studied to date is the relationship between OSA and systemic inflammation. In this respect, OSA has recently been associated with diseases with a great inflammatory burden, such as psoriasis [8] and other autoimmune disorders [9]. The relative scientific youthfulness of OSA means that new action mechanisms and previously unknown associations with other diseases are now being increasingly discovered. One particular piece of news was sprung on the scientific community at recent international congresses, creating quite a stir: some studies in both animals [10–12] and humans [13–15], undertaken almost simultaneously, had found an association between OSA and cancer.

There have been reports of a relationship between different aspects of nonapnoeic sleep disorders, particularly sleep duration, and cancer. Specifically, some studies have shown an association between …
Synergy of p53 and Rb Deficiency in a Conditional Mouse Model for Metastatic Prostate Cancer
Authors: Zongxiang Zhou, Andrea Flesken-Nikitin, David C. Corney, Wei Wang, David W. Goodrich, Pradip Roy-Burman, Alexander Yu. Nikitin
Journal: Cancer Research (2006)

Abstract Pathways mediated by p53 and Rb are frequently altered in aggressive human cancers, including prostate carcinoma. To test directly the roles of p53 and Rb in prostate carcinogenesis, we have conditionally inactivated these genes in the prostate epithelium of the mouse. Inactivation of either p53 or Rb leads to prostatic intraepithelial neoplasia developing from the luminal epithelium by 600 days of age. In contrast, inactivation of both genes results in rapidly developing (median survival, 226 days) carcinomas showing both luminal epithelial and neuroendocrine differentiation. The resulting neoplasms are highly metastatic, resistant to androgen depletion from the early stage of development, and marked with multiple gene expression signatures commonly found in human prostate carcinomas. Interestingly, gains at 4qC3 and 4qD2.2 and loss at 14qA2-qD2 have been consistently found by comparative genomic hybridization. These loci contain such human cancer–related genes as Nfib, L-myc, and Nkx3.1, respectively. Our studies show a critical role for p53 and Rb deficiency in prostate carcinogenesis and identify likely secondary genetic alterations. The new genetically defined model should be particularly valuable for providing new molecular insights into the pathogenesis of human prostate cancer. (Cancer Res 2006; 66(16): 7889-98)
Gene Therapy for Attenuating Cardiac Allograft Arteriopathy Using Ex Vivo E2F Decoy Transfection by HVJ-AVE–Liposome Method in Mice and Nonhuman Primates
Authors: Motohiro Kawauchi, Jun-ichi Suzuki, Ryuichi Morishita, Yuko Wada, Atsushi Izawa, Naruya Tomita, Jun Amano, Yasufumi Kaneda, Toshio Ogihara, Shinichi Takamoto, Mitsuaki Isobe
Journal: Circulation Research (2000)

Abstract —Cardiac allograft arteriopathy, which limits the long-term survival of recipients, is characterized by diffuse intimal thickening composed of proliferative smooth muscle cells. The transcription factor E2F plays a pivotal role in the coordinated transcription of cell-cycle regulatory genes. To test the hypothesis that double-stranded DNA with specific affinity for E2F (E2F decoy) is effective in preventing intimal hyperplasia, we performed ex vivo single intraluminal delivery of E2F decoy into cardiac allografts of mice and Japanese monkeys using the hemagglutinating virus of Japan (HVJ) artificial viral envelope–liposome method. In murine models, antisense cyclin-dependent kinase 2 (cdk2) kinase oligodeoxynucleotide (ODN) and no transfers were performed to compare the effects. Severe intimal thickening was observed, and multiple cell-cycle regulatory genes were enhanced in untreated allografts. E2F decoy prevented neointimal formation and suppressed these genes for up to 8 weeks, whereas antisense cdk2 kinase ODN had limited effects. In primate models, E2F decoy dramatically prevented neointimal thickening and suppressed multiple cell-cycle regulatory genes, whereas intimal thickening developed in the nontransfected or mismatch decoy-transfected allografts. Gel mobility shift assay proved the specific effects of E2F decoy, and reverse transcriptase–polymerase chain reaction documented that neither complication nor dissemination of HVJ into other organs was observed. We demonstrate that ex vivo gene delivery to allografts is a potent strategy to modify allograft gene expression, resulting in prevention of graft arteriopathy without systemic adverse effects.
Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease
Authors: S A Harrison, D Oliver, H L Arnold, S Gogia, B A Neuschwander-Tetri
Journal: Gut (2008)

Clinical predictors of advanced non-alcoholic liver disease (NAFLD) are needed to guide diagnostic evaluation and treatment.To better understand the demographics of NAFLD and risk factors for advanced disease, this study analysed 827 patients with NAFLD at two geographically separate tertiary medical centres.The cohort was 51% female and had a median body mass index (BMI) of 33 kg/m(2); 3% had a normal BMI. Common co-morbidities included hypertension (60%) and diabetes (35%); insulin resistance was present in 91% and advanced fibrosis in 24% of patients. When comparing patients with no fibrosis or mild fibrosis to those with advanced fibrosis, BMI > or = 28 kg/m(2), age > 50 years, and aspartate transaminase/alanine aminotransferase (AST/ALT) ratio > or = 0.8, a quantitative assessment check index (QUICKI) score < 0.294 (equivalent to homeostasis model assessment (HOMA) > 6.2) and the presence of diabetes mellitus (DM) were individually associated by univariate analysis with odds ratios (ORs) of > or = 2.4 for advanced fibrosis. Based on the results of forced entry logistic regression analysis, three variables were combined in a weighted sum (BMI > or = 28 = 1 point, AAR of > or = 0.8 = 2 points, DM = 1 point) to form an easily calculated composite score for predicting advanced fibrosis called the BARD score. A score of 2-4 was associated with an OR for advanced fibrosis of 17 (confidence interval 9.2 to 31.9) and a negative predictive value of 96%.Insulin resistance and its co-morbidities are often present in patients with NAFLD. An easily calculated score based on readily available clinical data can reliably exclude the presence of advanced fibrosis in these patients, particularly among non-diabetics.
Prevention of Distal Embolization During Saphenous Vein Graft Lesion Angioplasty
Authors: Mauro Carlino, Joseph De Gregorio, Carlo Di Mario, Angelo Anzuini, Flavio Airoldi, Remo Albiero, Carlo Briguori, Aniruddha Dharmadhikari, Imad Sheiban, Antonio Colombo
Journal: Circulation (1999)

Background —Repeat coronary artery bypass graft surgery (CABG) is associated with a high morbidity and mortality, rendering percutaneous treatment of saphenous vein graft (SVG) lesions an attractive alternative. However, percutaneous interventions of degenerated SVGs carries high risk of distal embolization. Methods and Results —This study reports our initial experience with the PercuSurge GuardWire, a new device developed to prevent embolization during treatment of degenerated SVG. This device consists of a 190-cm-long, hollow 0.014-in guidewire with a central lumen connected to a distal occlusion balloon. A dedicated inflation device (the MicroSeal Adapter) was used to inflate the distal balloon and maintain complete lumen occlusion during balloon dilatation and stent implantation. A monorail aspiration catheter, connected to a vacuum syringe, was used to evacuate atherosclerotic and thrombotic debris. Angioplasty with stent implantation was performed in 15 degenerated SVGs (18 lesions). Procedural success was achieved in all patients with normal postprocedure flow (Thrombolysis in Myocardial Infarction grade 3). No distal embolization was observed. There were no major in-hospital adverse clinical events, including Q-wave or non–Q-wave myocardial infarction, emergency CABG, or death. All patients were asymptomatic at discharge. Conclusions —This preliminary series supports the feasible use of the PercuSurge GuardWire for retrieval of plaque debris and prevention of embolization in degenerated SVGs. The good tolerance of temporary occlusions without angiographic or clinical evidence of distal embolization represents encouraging early findings.
Asymmetric Intense Bilateral Adrenal Uptake on [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Patient With Solitary Pulmonary Nodule
Authors: Mei-Fang Cheng, Mong-Wei Lin, Chen-Tu Wu, Shyang-Rong Shih, Yen-Wen Wu, Kai-Yuan Tzen, Rouh-Fang Yen
Journal: Journal of Clinical Oncology (2012)

A 70-year-old woman was admitted to our hospital because of progressive facial and bilateral leg swelling and weight gain for 2 months.The long-standing mild diabetes mellitus and hypertension of the patient became difficult to control recently.There was no history of drug use, fever, or other discomfort.On examination, she presented with Cushingoid features (ie, moon face, acne, eyelid swelling, prominent pitting edema of bilateral legs, and skin atrophy) and high blood pressure up to 197/91 mmHg.Laboratory results showed severe hypokalemia (serum potassium, 1.9 mmol/L [reference range, 3.5 to 5.3 mmol/L]), increased fasting glucose (176 mg/dL), lower thyroid-stimulating hormone (0.007 U/mL [reference range, 0.1 to 4.5 U/mL]), increased serum cortisol with loss of diurnal secretion (am: 40.5 g/dL; pm: 47.4 g/dL [reference range, am: 5 to 24 g/dL; pm: 2.5 to 12.5 g/dL]), and increased adrenocorticotropic hormone (ACTH) level (am: 266 pg/mL; pm: 143 pg/mL [reference range, 10 to 65 pg/mL]).The follicle-stimulating hormone and luteinizing hormone levels were within the normal range but close to the lower limits.Plasma ACTH and cortisol were not suppressible by either low or high doses of dexamethasone.These presenting clinical pictures and endocrine data suggested a clinical diagnosis of ectopic ACTH syndrome.A pituitary magnetic resonance imaging scan was normal.The patient was treated with potassium supplement, vasodilator, and insulin therapy.A right middle lobe (RML) lung tumor of 1.67 cm and thickening of bilateral adrenal glands were found in the
Alterations in Distribution of Blood Flow to the Lung's Diffusion Surfaces During Exercise
Authors: Carroll E. Cross, Henry Gong, Cornelius J. Kurpershoek, Jerry R. Gillespie, Richard W. Hyde
Journal: Journal of Clinical Investigation (1973)

We measured simultaneously, by single breath methods, pulmonary capillary blood flow (Q(c)), carbon monoxide diffusing capacity (DL(CO)), and isotopic oxygen ((18)O(18)O) diffusing capacity (DL(18) (O2)) in five normal males during conditions of rest and moderate exercise at mixed venous O(2) tensions (PO(2) 33-44 mm Hg). During moderate exercise at a work load of 100 W. pulmonary capillary blood flow increased from 6.9+/-1.5 to 12.9+/-3.4 min(-1) and DL(18) (O2) increased from 25+/-4 to 43+/-3 ml.min(-1).mm Hg(-1), whereas DL(CO) showed no significant change (45+/-5 to 49+/-10 ml.min(-1).mm Hg(-1)). DL(18) (O2) increased proportionally to Q(c) (r = 0.74), where DL(CO) did not (r = 0.08). The greater increase in DL(18) (O2) during exercise can be explained by a more homogeneous diffusion/perfusion (DL(O2)/Q(c)) distribution in the individual respiratory exchange units during exercise. This improved distribution of DL(O2)/Q(c) acts to help prevent an increase in alveolar-arterial O(2) tension difference from developing despite the decrease in pulmonary erythrocyte transit times that occur during exercise. The insignificant rise in DL(CO) with exercise under these hypoxic breathholding conditions may result from pulmonary vasomotor responses to short-term hypoxia or from relative insensitivity of DL(CO) to moderate levels of exercise.
Diagnosis of CTEPH versus IPAH using capillary to end-tidal carbon dioxide gradients
Authors: S.J. Scheidl, C. Englisch, G. Kovacs, F. Reichenberger, R. Schulz, A. Breithecker, H-A. Ghofrani, W. Seeger, H. Olschewski
Journal: European Respiratory Journal (2011)

Chronic thromboembolic pulmonary hypertension (CTEPH) represents an important differential diagnosis to idiopathic pulmonary arterial hypertension (IPAH). We hypothesised that the capillary to end-tidal carbon dioxide gradient at rest and during exercise might help differentiate CTEPH from IPAH. Patients who presented with unequivocal IPAH or CTEPH according to ventilation/perfusion scanning, pulmonary angiography, computed tomography and right heart catheterisation were included in this retrospective study and compared with healthy controls. 21 IPAH patients and 16 CTEPH patients fulfilled the inclusion criteria. Haemodynamics and peak oxygen uptake were comparable, but respiratory rates at rest and during exercise were significantly higher in CTEPH than in IPAH. End-tidal carbon dioxide was significantly lower in CTEPH versus IPAH at rest and during exercise, while capillary carbon dioxide values were similar. Correspondingly, capillary to end-tidal carbon dioxide gradients were significantly increased in CTEPH versus IPAH at rest and during exercise (median (range) 8.6 (3.0-13.7) versus 4.4 (0.9-9.0) (p<0.001) and 9.3 (3.3-13.1) versus 4.1 (0.0-8.8) mmHg (p<0.001), respectively). Although these values were closer to normal in IPAH they were still significantly elevated compared with healthy controls (2.3 (-4.8-8.1) and -1.9 (-5.7-6.2) mmHg, respectively). Capillary to end-tidal carbon dioxide gradients may help to distinguish CTEPH from IPAH based on resting and exercise values.
Diabetes Undermines Estrogen Control of Inducible Nitric Oxide Synthase Function in Rat Aortic Smooth Muscle Cells Through Overexpression of Estrogen Receptor-β
Authors: Adriana Maggi, Andrea Cignarella, Alessia Brusadelli, Chiara Bolego, Christian Pinna, Lina Puglisi
Journal: Circulation (2003)

Previous reports from our group have shown that 17beta-estradiol reduces the synthesis and activity of inducible nitric oxide synthase (iNOS) in rat aortic smooth muscle cells (SMC) in response to inflammatory mediators. In this study, we investigated the effect of 17beta-estradiol on iNOS function in aortic SMC from streptozotocin-diabetic rats.Comparative analysis of NO release and of iNOS mRNA and protein content after 24-hour stimulation with a cytokine mixture revealed milder iNOS activation in diabetic than in control SMC. Furthermore, 17beta-estradiol dose-dependently blocked iNOS synthesis and activity in control but not in diabetic SMC. The defective estrogen response in diabetic SMC at 24 hours could not be attributed to reduced expression of estrogen receptors (ER). In fact, mRNA and protein levels of ERalpha and, to a greater extent, of ERbeta, were increased in diabetic compared with nondiabetic SMC. Cytokines decreased ERalpha and ERbeta expression in both groups. However, 17beta-estradiol dose-dependently restored the expression of ERalpha but further downregulated that of ERbeta, indicating a differential regulation of ER isoforms.Estrogenic control of iNOS was impaired in diabetic SMC. This was associated with a larger increase of ERbeta than of ERalpha protein, whereas 17beta-estradiol regulated the two isoforms in an opposite fashion. Thus, modifications in the estrogen modulation of iNOS and in the expression pattern of ER may be involved in diabetic vascular dysfunction.
Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes
Authors: Denis Azzopardi, Brenda Strohm, Neil Marlow, Peter Brocklehurst, Aniko Deierl, Oya Eddama, Julia Goodwin, Henry L. Halliday, Edmund Juszczak, Olga Kapellou, Malcolm Levene, Louise Linsell, Omar Omar, Marianne Thoresen, Nora Tusor, Andrew Whitelaw, A. David Edwards
Journal: New England Journal of Medicine (2014)

In the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), newborns with asphyxial encephalopathy who received hypothermic therapy had improved neurologic outcomes at 18 months of age, but it is uncertain whether such therapy results in longer-term neurocognitive benefits.We randomly assigned 325 newborns with asphyxial encephalopathy who were born at a gestational age of 36 weeks or more to receive standard care alone (control) or standard care with hypothermia to a rectal temperature of 33 to 34°C for 72 hours within 6 hours after birth. We evaluated the neurocognitive function of these children at 6 to 7 years of age. The primary outcome of this analysis was the frequency of survival with an IQ score of 85 or higher.A total of 75 of 145 children (52%) in the hypothermia group versus 52 of 132 (39%) in the control group survived with an IQ score of 85 or more (relative risk, 1.31; P=0.04). The proportions of children who died were similar in the hypothermia group and the control group (29% and 30%, respectively). More children in the hypothermia group than in the control group survived without neurologic abnormalities (65 of 145 [45%] vs. 37 of 132 [28%]; relative risk, 1.60; 95% confidence interval, 1.15 to 2.22). Among survivors, children in the hypothermia group, as compared with those in the control group, had significant reductions in the risk of cerebral palsy (21% vs. 36%, P=0.03) and the risk of moderate or severe disability (22% vs. 37%, P=0.03); they also had significantly better motor-function scores. There was no significant between-group difference in parental assessments of children's health status and in results on 10 of 11 psychometric tests.Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood. (Funded by the United Kingdom Medical Research Council and others; TOBY ClinicalTrials.gov number, NCT01092637.).
Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI
Authors: Jay L. Koyner, Andrew D. Shaw, Lakhmir S. Chawla, Eric A.J. Hoste, Azra Bihorac, Kianoush Kashani, Michael Haase, Jing Shi, John A. Kellum
Journal: Journal of the American Society of Nephrology (2014)

Tissue inhibitor metalloproteinase-2 (TIMP-2) and IGF-binding protein-7 (IGFBP7) have been validated for risk stratification in AKI. However, the association of urinary TIMP-2 and IGFBP7 with long-term outcomes is unknown. We evaluated the 9-month incidence of a composite end point of all-cause mortality or the need for RRT in a secondary analysis of a prospective observational international study of critically ill adults. Two predefined [TIMP-2]⋅[IGFBP7] cutoffs (0.3 for high sensitivity and 2.0 for high specificity) for the development of AKI were evaluated. Cox proportional hazards models were used to determine risk for the composite end point. Baseline [TIMP-2]⋅[IGFBP7] values were available for 692 subjects, of whom 382 (55.2%) subjects developed stage 1 AKI (defined by Kidney Disease Improving Global Outcomes guidelines) within 72 hours of enrollment and 217 (31.4%) subjects met the composite end point. Univariate analysis showed that [TIMP-2]⋅[IGFBP7]>2.0 was associated with increased risk of the composite end point (hazard ratio [HR], 2.11; 95% confidence interval [95% CI], 1.37 to 3.23; P<0.001). In a multivariate analysis adjusted for the clinical model, [TIMP-2]⋅[IGFBP7] levels>0.3 were associated with death or RRT only in subjects who developed AKI (compared with levels≤0.3: HR, 1.44; 95% CI, 1.00 to 2.06 for levels>0.3 to ≤2.0; P=0.05 and HR, 2.16; 95% CI, 1.32 to 3.53 for levels>2.0; P=0.002). In conclusion, [TIMP-2]⋅[IGFBP7] measured early in the setting of critical illness may identify patients with AKI at increased risk for mortality or receipt of RRT over the next 9 months.