Miracle-dz/UniFAR-FTUs huggingface dataset:
Amyloid Efflux Transporter Expression at the Blood-Brain Barrier Declines in Normal Aging

Reduced clearance of amyloid &bgr; peptides (A&bgr;) across the blood-brain barrier contributes to amyloid accumulation in Alzheimer disease. Amyloid &bgr; efflux transport is via the endothelial low-density lipoprotein receptor-related protein 1 (LRP-1) and P-glycoprotein (P-gp), whereas A&bgr; influx transport is via the receptor for advanced glycation end products. Because age is the major risk factor for developing Alzheimer disease, we measured LRP-1 and P-gp expression and associated transporter expression with A&bgr; accumulation in aging rats. Quantitative LRP-1 and P-gp microvessel expression was measured by immunohistochemistry (IHC); LRP-1 and P-gp expression were assessed in microvessel isolates by Western blotting. There was an age-dependent loss of capillary LRP-1 across all ages (3-36 months) by IHC (linear trend p = 0.0004) and between 3 and 20 months by Western blotting (linear trend p < 0.0001). There was a late (30-36 months) P-gp expression loss by IHC (p < 0.05) and Western blotting (p = 0.0112). Loss ofLRP-1 correlated with A&bgr;42 accumulation (p = 0.0121) and verynearly with A&bgr;40 (p = 0.0599) across all ages. Expression of LRP-1correlated negatively with the expression of receptor for advanced glycation end products (p < 0.0004). These data indicate that alterations in LRP-1 and P-gp expression seem to contribute progressively to A&bgr; accumulation in aging.
Expanding access to hepatitis C virus treatment—Extension for Community Healthcare Outcomes (ECHO) project: Disruptive innovation in specialty care

The Extension for Community Healthcare Outcomes (ECHO) Model was developed by the University of New Mexico Health Sciences Center as a platform to deliver complex specialty medical care to underserved populations through an innovative educational model of team‐based interdisciplinary development. Using state‐of‐the‐art telehealth technology, best practice protocols, and case‐based learning, ECHO trains and supports primary care providers to develop knowledge and self‐efficacy on a variety of diseases. As a result, they can deliver best practice care for complex health conditions in communities where specialty care is unavailable. ECHO was first developed for the management of hepatitis C virus (HCV), optimal management of which requires consultation with multidisciplinary experts in medical specialties, mental health, and substance abuse. Few practitioners, particularly in rural and underserved areas, have the knowledge to manage its emerging treatment options, side effects, drug toxicities, and treatment‐induced depression. In addition, data were obtained from observation of ECHO weekly clinics and database of ECHO clinic participation and patient presentations by clinical provider. Evaluation of the ECHO program incorporates an annual survey integrated into the ECHO annual meeting and routine surveys of community providers about workplace learning, personal and professional experiences, systems and environmental factors associated with professional practice, self‐efficacy, facilitators, and barriers to ECHO. The initial survey data show a significant improvement in provider knowledge, self‐efficacy, and professional satisfaction through participation in ECHO HCV clinics. Clinicians reported a moderate to major benefit from participation. We conclude that ECHO expands access to best practice care for underserved populations, builds communities of practice to enhance professional development and satisfaction of primary care clinicians, and expands sustainable capacity for care by building local centers of excellence. (HEPATOLOGY 2010)
A Mouse Model of Blast Injury to Brain: Initial Pathological, Neuropathological, and Behavioral Characterization

The increased use of explosives in recent wars has increased the number of veterans with blast injuries. Of particular interest is blast injury to the brain, and a key question is whether the primary overpressure wave of the blast is injurious or whether brain injury from blast is mostly due to secondary and tertiary effects. Using a shock tube generating shock waves comparable to open-field blast waves, we explored the effects of blast on parenchymatous organs of mice with emphasis on the brain. The main injuries in nonbrain organs were hemorrhages in the lung interstitium and alveolar spaces and hemorrhagic infarcts in liver, spleen, and kidney. Neuropathological and behavioral outcomes of blast were studied at mild blast intensity, that is, 68 ± 8 kPag (9.9 ±1.2 psig) static pressure, 103 kPag (14.9 psig) total pressure and 183 ± 14 kPag (26.5 ± 2.1 psig) membrane rupturepressure. Under these conditions, weobserved multifocal axonal injury, primarily in the cerebellum/brainstem, the corticospinal system, and the optic tract. We also found prolonged behavioral and motor abnormalities, including deficits in social recognition and spatial memory and in motor coordination. Shielding of the torso ameliorated axonal injury and behavioral deficits. These findings indicate that long CNS axon tracts are particularly vulnerable to the effects of blast, even at mild intensities that match the exposure of most veterans in recent wars. Prevention of some of these neurological effects by torso shielding may generate new ideas as to how to protect military and civilian populations in blast scenarios.
Diagnosis and management of hyponatraemia in hospitalised patients

Hyponatraemia is a commonly encountered electrolyte abnormality in hospitalised patients and is associated with significant morbidity and mortality. The fact that most cases of hyponatraemia are the result of water imbalance rather than sodium imbalance underscores the role of antidiuretic hormone (ADH) in the pathophysiology. Hyponatraemia can be classified according to the measured plasma osmolality as isotonic, hypertonic or hypotonic. Hyponatraemia with a normal plasma osmolality usually indicates pseudohyponatraemia, while hyponatraemia because of a high plasma osmolality is typically caused by hyperglycaemia. After excluding isotonic and hypertonic causes, hypotonic hyponatraemia is further classified according to the volume status of the patient as hypovolaemic, hypervolaemic or euvolaemic. Hypovolaemic hyponatraemia is accompanied by extracellular fluid (ECF) volume deficit, while hypervolaemic hyponatraemia manifests with ECF volume expansion. The syndrome of inappropriate ADH (SIADH) should be suspected in any patient with euvolaemic hyponatraemia with a urine osmolality above 100 mOsm/kg and urine sodium concentration above 40 mEq/l. In the management of any hyponatraemia regardless of the patient’s volume status, it is advised to restrict free water and hypotonic fluid intake. Hypertonic saline and vasopressin antagonists can be used to correct symptomatic hyponatraemia. The rate of correction is dependent upon the duration, degree of hyponatraemia and the presence or absence of symptoms. Symptomatic acute hyponatraemia (< 48 h) is a medical emergency requiring rapid correction to prevent the worsening of brain oedema. In asymptomatic patients with chronic hyponatraemia (> 48 h or unknown duration), fluid restriction and close monitoring alone are sufficient, while a slow correction by 0.5 mEq/l/h may be attempted in symptomatic patients. Excessive rapid correction should be avoided in both acute and chronic hyponatraemia, because it can lead to irreversible neurological complications including central osmotic demyelination.
Monotherapy Insufficient in Severe Anxiety? Predictors and Moderators in the Child/Adolescent Anxiety Multimodal Study

This secondary analysis of the Child/Adolescent Anxiety Multimodal Study (CAMS) used baseline patient characteristics to identify prognostic subgroups of children based on likelihood of remission. We also investigated predictors and moderators of outcome. CAMS randomized 488 youths with generalized, social, and separation anxiety disorders to cognitive behavioral therapy (CBT), sertraline, both, or pill placebo. Outcomes were Week 12 child, parent, and independent evaluator (IE) ratings of child anxiety. We used receiver operating characteristics analysis and stepwise regression to identify predictors and moderators of outcome. Severe anxiety, lower socioeconomic status, and comorbid obsessive-compulsive disorder predicted higher IE-rated anxiety posttreatment; child-rated social anxiety predicted poorer outcomes reported by all informants. Regarding moderators, Hispanic ethnicity predicted higher IE-rated anxiety after CBT and higher parent-rated anxiety after sertraline. In youths with severe anxiety (Pediatric Anxiety Rating Scale ≥ 20, <italic>n</italic> = 220), combination treatment increased remission (relative risk [RR] = 2.85, <italic>p</italic> < .001), 95% confidence interval (CI) [1.51, 5.39], whereas CBT (RR = 1.55, <italic>p</italic> = .20), 95% CI [0.77, 3.10], and sertraline (RR = 1.27, <italic>p</italic> = .53), 95% CI [0.59, 2.73], did not significantly increase remission relative to placebo. These are the first findings demonstrating that a combination of CBT and a selective serotonin reuptake inhibitor, not monotherapy, is likely key for achieving remission in severe anxiety. CAMS was not powered to detect treatment efficacy after stratification by anxiety severity, so further research is needed regarding effective treatments in severe anxiety. Our main effect findings suggest youth with severe anxiety (especially social phobia), low socioeconomic status and obsessive-compulsive disorder benefit less from current first-line treatments relative to other anxious youth. ClinicalTrials.gov: NCT00052078.
Validation of MRI Measurement of Cardiac Output in the Dog: The Effects of Dobutamine and Minoxidil

The use of magnetic resonance imaging (MRI) for the measurement of cardiac output parameters in anesthetized adult male beagle dogs has been validated against a widely accepted thermodilution method. Using a multislice cine gradient echo MRI method to acquire images of the entire heart, left ventricular lumen volumes were measured at systole and diastole in seven animals. Cardiac output correlated well (R 2 = 0.88) with thermodilution measurements made in a parallel manner, both before and during acute stimulation with the inotrope dobutamine. In a chronic study of changes in cardiac morphology and function brought about by the antihypertensive minoxidil, MRI reliably detected the expected increases in stroke volume (28%) and cardiac output (58%) resulting from neural reaction to decreased blood pressure. Left ventricular lumen enlarged as well in response to fluid retention and plasma volume increase. Two in four minoxidil-treated animals also developed clear MRI-visible pericardial effusion.
Nuclear factor κB up‐regulation of CCAAT/enhancer‐binding protein β mediates hepatocyte resistance to tumor necrosis factor α toxicity

The sensitization of hepatocytes to cell death from tumor necrosis factor α (TNFα) underlies many forms of hepatic injury, including that from toxins. Critical for hepatocyte resistance to TNFα toxicity is activation of nuclear factor κB (NF‐κB) signaling, which prevents TNFα‐induced death by the up‐regulation of protective proteins. To further define the mechanisms of hepatocyte sensitization to TNFα killing, immunoblot analysis comparing livers from mice treated with lipopolysaccharide (LPS) alone or LPS together with the hepatotoxin galactosamine (GalN) was performed to identify TNFα‐induced protective proteins blocked by GalN. Levels of CCAAT/enhancer‐binding protein β (C/EBPβ) were increased after LPS treatment but not GalN/LPS treatment. In a nontransformed rat hepatocyte cell line, TNFα‐induced increases in C/EBPβ protein levels were dependent on NF‐κB–mediated inhibition of proteasomal degradation. Pharmacological inhibition of c‐Jun N‐terminal kinase (JNK) did not affect C/EBPβ degradation, indicating that the process was JNK‐independent. C/EBPβ functioned to prevent cell death as adenoviral C/EBPβ overexpression blocked TNFα‐induced apoptosis in cells sensitized to TNFα toxicity by NF‐κB inhibition. C/EBPβ inhibited TNFα‐induced caspase 8 activation and downstream mitochondrial cytochrome c release and caspase 3 and caspase 7 activation. Studies in primary hepatocytes from c/ebpβ−/− mice confirmed that loss of C/EBPβ increased death from TNFα. c/ebpβ−/− mice were also sensitized to liver injury from a nontoxic dose of LPS or TNFα. The absence of jnk2 failed to reverse the GalN‐induced block in C/EBPβ induction by LPS, again demonstrating that C/EBPβ degradation was JNK‐independent. Conclusion: C/EBPβ is up‐regulated by TNFα and mediates hepatocyte resistance to TNFα toxicity by inhibiting caspase‐dependent apoptosis. In the absence of NF‐κB signaling, proteasomal degradation of C/EBPβ is increased by a JNK‐independent mechanism and promotes death from TNFα. (HEPATOLOGY 2010;.)
Beneficial Effect of Phosphodiesterase-5 Inhibitor in Experimental Inflammatory Bowel Disease; Molecular Evidence for Involvement of Oxidative Stress

ABSTRACT Inflammatory bowel disease (IBD) is a common and chronic gastrointestinal disorder characterized by intestinal inflammation and mucosal tissue damage. Reactive oxygen metabolites (ROMs) play a pathogenic role in IBD. We aimed to examine the protective effect of sildenafil, a cGMP phosphodiesterase inhibitor, in the experimental mouse model of IBD. Intrarectal instillation of acetic acid was used to induce IBD. Prednisolone was used as the standard drug for comparison. Sildenafil was used at doses of 0.75, 1.5, and 3 mg/kg. Biochemicals and macroscopic and microscopic examinations of colonic tissue were performed. Results indicated that activity of myeloperoxidase (MPO) and lipid peroxidation product (TBARS) markers of oxidative stress are increased in acetic acid-treated groups and are recovered by sildenafil pretreatment and prednisolone. Sildenafil- (1.5 and 3 mg/kg) and prednisolone-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared to the acetic acid-treated group. The beneficial effect of sildenafil (3 mg/kg) was comparable to that of prednisolone. It is concluded that sildenafil is helpful in the management of IBD, which is presumably related to its strong antioxidative stress potential mediated through enhanced cGMP. Results of proper clinical trials will determine the possible efficacy of phosphodiesterase-5 inhibitors in human IBD.
Online Coaching for a Lower Limb Physical Activity Program for Individuals at Home with a History of Venous Ulcers

The goal of this preliminary study was to test a structured home-based chair physical activity (PA) intervention, using a "live" coach on the feasibility of using the Internet to work with patients who had a history of leg ulcers. A 10- to 15-minute lower limb PA protocol using resistance tubing and foot pushing and peddling devices were used in the study while the coach watched patients perform the activities three times over a 7-day period. The Internet for "live" coaching was found to be feasible and patient-acceptable.
The Effect of Etoricoxib, a Cyclooxygenase-2–Specific Inhibitor, on the 1,2-Dimethylhydrazine–Administered Rat Intestinal Membrane Structure and Function

ABSTRACT To gain insight into the chemopreventive effects of etoricoxib, which is a selective inhibitor of cycloxygenase-2, a study was carried out in the procarcinogen 1,2-dimethylhydrazine–treated rat intestine. The male Sprague Dawley rats were divided into three different groups. Group 1 served as control (vehicle treated). All animals in Group 2 were given a weekly subcutaneous injection of 1,2-dimethylhydrazine (DMH; 30 mg/kg body weight) for 6 weeks. Group 3 animals were given an additional oral dose of etoricoxib (6 mg/kg body weight) along with weekly DMH injections for 6 weeks. At the end of 6 weeks of treatments, the results indicated significant alterations in the biochemical parameters, membrane lipid composition, and membrane fluorescence studies of the intestine in the presence of DMH, which were recovered nearly to the control level and, therefore, may suggest the chemopreventive efficacy of etoricoxib against the experimental intestinal cancer in rats.
Viewpoints on the providing of information about liver disease to patients with chronic liver disease in classes on liver disease

関西22病院にて肝臓病教室に関するアンケート調査を行なった．対象は，医療者55名，慢性肝疾患患者176名．肝臓病教室を定期開催しているのは7施設，経験はあるが現在未施行2施設，未施行13施設であった．継続できない理由は，マンネリ化や慣れたスタッフの配置換えによるパワーダウン，教室の効果を把握しにくいなどで，開始できない理由は，準備などの時間がないが最も多かった．医療者と患者とも，各々95%，94%が教室は必要と回答した．提供すべき情報は，医療者は1位：肝臓病とは，2位：治療方法，3位：合併症とその対策/肝臓の働き，患者側は1位：治療方法，2位：治療効果，3位：食事療法を上位に挙げた．教室のメリットは，両者とも1位：自己管理の向上，2位：治療に対して前向きな姿勢になれる，3位：不安の軽減，と一致した．有効な患者教育の普及のためには，方法論の普及，有用な情報の種類や提供方法の検討，情報提供による効果の評価方法を確立し医療者のやる気の維持につなげるなどが必要と考えられた．
Apoptotic cells attenuate fulminant hepatitis by priming Kupffer cells to produce interleukin‐10 through membrane‐bound TGF‐β

The liver, a unique tolerogenic organ, is regarded as the site to trap and destroy aging erythrocytes and activated T cells. However, to date, the mechanisms for why the liver is tolerogenic and whether liver Kupffer cells (KC) are critical phagocytes for apoptotic cells (AC) contributing to the liver immunosuppression remain unclear. Here we report that KC is the main phagocyte for AC in the liver. Contact of AC inhibits proinflammatory cytokine but enhances anti‐inflammatory cytokine production of KC in response to lipopolysaccharide (LPS) stimulation. Membrane‐bound transforming growth factor (TGF)‐β on AC is responsible for the increased production of interleukin (IL)‐10 in KC through extracellular signal‐regulated kinase (ERK) activation via the Smad3 pathway. Importantly, KC‐derived IL‐10 is critical for AC infusion‐mediated protection of endotoxin‐induced fulminant hepatitis through suppression of tumor necrosis factor (TNF)‐α and nitric oxide (NO) production from KC and consequently attenuation of KC‐mediated cytolysis of hepatocytes. Conclusion: AC can be preferentially phagocytosed by KC in the liver, leading to attenuation of fulminant hepatitis through IL‐10‐mediated suppression of KC‐derived inflammatory TNF‐α and NO production. These findings demonstrate that priming of KC by AC may contribute to maintain liver immunosuppression, providing a new mechanistic explanation for how immune homeostasis is maintained in the liver. (HEPATOLOGY 2011.)
Psychometric Properties and Construct Validity of the Knowledge Information Profile–Coumadin

Background: Oral anticoagulation therapy using Coumadin (warfarin) requires significant patient involvement. Limited validated instruments exist to test patient knowledge of Coumadin, and low health literacy may impede patient self-management. Objective: This article reports the psychometric testing of the Knowledge Information Profile–Coumadin (KIP-C20) to determine (a) minimum number of items and dimensions, (b) reliability, and (c) construct validity. Methods: Participants (N = 192) were recruited from outpatient pharmacist-directed anticoagulation clinics associated with an urban teaching hospital in the Midwest United States. Instruments were the Animal Naming test (AN), Rapid Estimate of Adult Literacy in Medicine (REALM), and KIP-C20. Multidimensional item response theory modeling and exploratory factor analyses were used to determine the best fitting model. Results: The final instrument, renamed KIP-C14, with 3 factors and 14 items, had a good fit to data (M2 = 96.49, P < .0001; root mean square error of approximation = .04), and all factor loadings were . 3 or larger. Internal consistency reliability was . 65; test–retest correlation was . 67. The KIP-C14 correlated positively, as expected, with years of Coumadin treatment. Subscales were differentially correlated with sociodemographic variables. Conclusions: The KIP-C14 had nearly identical, slightly higher reliability than the KIP-C20. Still, reliability was lower than expected, indicating a promising clinical assessment scale in need of further refinement.
Inmate Prerelease Assessment (IPASS) Aftercare Placement Recommendation as a Predictor of Rural Inmate's 12-step Attendance and Treatment Entry Postrelease

The purpose of this study is to use the Criminal Justice Drug Abuse Treatment Studies' (CJ-DATS) Inmate Prerelease Assessment (IPASS), which recommends either intensive or nonintensive treatment after release, to predict rural offenders' 12-step attendance and treatment entry within six months of release from prison. IPASS scores indicated that 52% of rural offenders needed intensive treatment upon community re-entry. In bivariate analyses, rural offenders with an intensive aftercare placement recommendation were significantly younger, more likely to have been employed more months in the year prior to incarceration, to have ever injected drugs, and to have ever received outpatient substance abuse treatment. The variables which were significant at the bivariate level were entered into two logistic multivariate models predicting 12-step attendance and treatment entry within six months of being released from prison. Age and having ever injected drugs were positive predictors of having attended a 12-step meeting, while the number of months legally employed was negatively related to 12-step attendance. In the treatment entry model, age increased the odds of entering formal treatment while having ever injected a drug decreased the odds. IPASS aftercare placement recommendation was not significant in either of the multivariate models. Findings from this study suggest that offenders re-entering rural communities may receive limited community-based continued care and future studies should explore geographic-specific treatment barriers. Implications for rural substance abuse treatment are provided.
293EXTRACORPOREAL LIFE SUPPORT FOR CARDIOGENIC SHOCK: INFLUENCE OF CONCOMITANT INTRA-AORTIC BALLOON COUNTERPULSATION

OBJECTIVES: Intra-aortic balloon counterpulsation (IABP) during extracorporeal life support (ECLS) for cardiogenic shock may improve pulsatility and coronary perfusion, thereby promoting recovery of cardiac function. However, the risks and benefits of IABP during ECLS in real clinical settings have not been evaluated. This study aims to evaluate the effect of IABP on the early outcome of ECLS for cardiogenic shock. METHODS: We evaluated 253 adult patients (aged 58.8 ± 15.3 [mean ± standard deviation] years, 154 males) undergoing ECLS for cardiogenic shock from January 2005 to August 2012. Of them, 60 patients underwent concomitant IABP (IABP group) and 193 underwent ECLS only (control group). In-hospital outcomes were compared using the inverse probability of treatment weighting based on propensity scores. RESULTS: The indications for ECLS were low cardiac output after cardiac surgery in 118 patients (46.6%), heart failure in 71 (28.1%), acute myocardial infarction in 49 (19.4%) and others in 15 (5.9%). Successful ECLS weaning rate was significantly higher in the IABP group than in the control group (61.7 vs 42.0%, P= 0.008); however, there was no significant difference in in-hospital mortality between the two groups (68.6 vs 72.0%, P= 0.58). After adjustment for propensity of treatment assignment conditional on baseline characteristics, the IABP group showed a decreased risk of weaning failure (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.28–0.92, P= 0.024) but with a similar risk of in-hospital mortality (OR 0.85; 95% CI 0.46–1.60; P= 0.62) compared with the control group. CONCLUSIONS: The use of IABP during ECLS increased a successful ECLS weaning rate, but was not translated into improved survival. Studies on larger populations may verify the survival effect of IABP during ECLS.