tbuckley/cabot-search huggingface dataset:
Abstract 17012: Mesencephalic Astrocyte-Derived Neurotrophic Factor is an Endoplasmic Reticulum Stress-Inducible Protein with Novel Roles as a Regulator of Cardiac Myocyte Growth
Authors: Winston T Stauffer, Brandi Bailey, Adrian Arrieta, Shirin Doroudgar, Christopher C Glembotski
Journal: Circulation (2014)

Most secreted and membrane proteins, including hormones, receptors, growth factors, ion channels, and calcium-handling proteins are made in the sarco/endoplasmic reticulum (SR/ER) of cardiac myocytes. Many forms of heart disease cause ER stress, leading to the misfolding of proteins made in the SR/ER and subsequent activation of the unfolded protein response (UPR). A major feature of the UPR is a genetic reprogramming that is designed to relieve misfolded protein toxicity in the ER; this adaptive UPR has not been well studied in the heart. Our transcriptome analysis of a transgenic mouse model in which the adaptive UPR can be conditionally activated in cardiac myocytes showed that the recently discovered ER-resident protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) was upregulated. MANF is a ubiquitously expressed, 158 amino acid protein that is not structurally related to any other protein. Moreover, the function of MANF is not well studied. We showed that MANF protects cardiac myocytes and mouse hearts from ischemia/reperfusion injury. We hypothesized that this protection is a result of a critical role for MANF in the adaptive UPR. To address this hypothesis, we studied the effects of altering MANF levels in HEK293 cells, neonatal rat ventricular myocytes (NRVM), and mouse hearts. MANF knockdown in cultured cells using siRNA resulted in an exaggerated UPR, as evidenced by upregulation of numerous proteins involved in the canonical ER stress response. Unexpectedly, MANF knockdown increased the size of both HEK293 cells and NRVM. To investigate the function of MANF in the heart, in vivo, we generated a mouse model in which a microRNA targeted to MANF (miMANF) is expressed in a cardiac-specific manner and decreases MANF levels by 80% in the heart. Adult miMANF mice showed an 11% increase in heart weight/tibia length and an unexpected enhancement of cardiac function, characterized by a 10% increase in fractional shortening. MANF knockdown in mouse hearts did not affect cardiac hypertrophy induced by angiotensin II administration or transaortic constriction-induced pressure overload. These results suggest that MANF is an adaptive UPR-inducible ER-resident protein and a novel regulator of cardiac myocyte and heart growth.
Doctors in Nigeria strike over wages
Authors: Chibuzo Odigwe
Journal: BMJ (2004)

Resident doctors in Nigeria's public hospitals have threatened to go on strike indefinitely if the government fails to meet their demands about wages. The threat comes from the National Association of Resident Doctors of Nigeria (NARD), the 5000 strong trade union that represents doctors below the rank of consultant practising in public hospitals in Nigeria.

To press home their point, the doctors embarked on what they called a “warning strike” between Monday and Tuesday this week. Commenting on the need to embark on the warning strike, the association's president, Jerry Oguzie said, “We have watched helplessly as our profession has been terribly bastardised, and infrastructural decay has overtaken our …
Abstract 3769: K-ras Silencing has diverse effect on the response of cells to chemotherapeutic drugs
Authors: Ladan Teimoori-Toolabi, Kayhan Azadmanesh, Mohammadreza Khorramizadeh, Saba Hashemi
Journal: Cancer Research (2014)

Abstract Introduction: Drug resistance in different types of cancer arise serious concerns in oncology. Different genes and signaling pathways are responsible for this resistance. K-ras is one of the important signaling pathways in cancer. This pathway is activated in 50% of all types of cancer. In this study we aimed to study the effect of silencing RAS signaling pathway on the response of Hct116 as a colon cancer cell line to 5-flurouracil and oxaliplatin as the common chemotherapeutic drugs. Materials and methods: Two oligonucleotides silencing the wild type k-ras were selected by different online programs such as Dharmcon, Invitrogen and Promega. After insertion of these oligonucleotides into psilencer neo2.1, they were transfected into HCT116 cell line. Thereafter the lethality of 5-fluouracil and oxaliplatin in these cells was assessed by XTT proliferation assay kit. Results: Plasmids containing oligonucleotides silencing wild type were named p565ks and p688ks according to the site of silencing within the k-ras mRNA. Quantitative PCR analysis showed that silencing k-ras was more profound in HCT565ks. After stably transfecting Hct116 cell line with these plasmids, these cells were named HCT565ks and HCT688ks. While the LC50 of 5-flurouracil for Hct116 was 13-15µM, for HCT565ks and HCT688ks, it was 37.5-40 µM and 22.5-25 µM. While the LC50 of oxaliplatin for HCT116 was 8.75 µM, in HCT565ks and HCT688ks LC50s were 0.35 µM and 0.3 µM. These data showed that silencing k-ras have made the cells more resistant to 5-flurouracil while it increased the sensitivity of cells to lethal effects of oxaliplatin. Conclusion: In conclusion silencing k-ras had different effects on the response of cells to different chemotherapeutic drugs. This can urge us to be more cautious about prescribing RAS inhibiting drugs as it may cause the cells to become more resistant to some chemotherapeutic drugs such as 5-flurouracil while they may be killed more by other drugs such as oxaliplatin. Citation Format: Ladan Teimoori-Toolabi, Kayhan Azadmanesh, Mohammadreza Khorramizadeh, Saba Hashemi. K-ras Silencing has diverse effect on the response of cells to chemotherapeutic drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3769. doi:10.1158/1538-7445.AM2014-3769
Hepatic Artery Ligation for Liver Cancer
Authors: Nicholas J. Petrelli, Arnold Mittelman
Journal: Liver Cancer (1985)

This chapter describes techniques for interrupting the blood supply to tumors metastatic to the liver and to primary tumors of the liver, and reviews the results observed with these methods. Generally, regional treatment of hepatic metastases has been limited to tumors that arise from the abdominal gastrointestinal tract. Hepatic-dominated metastases are observed more often in certain types of gastrointestinal tumors. For example, carcinomas of the esophagus rarely metastasize solely to the liver, whereas colorectal, carcinoid tumors of the gastrointestinal tract, islet cell tumors of the pancreas, and leiomyosarcomas of the intestinal tract have a unique predisposition for hepatic-only metastases. Isolated hepatic metastases are common for choroidal or retinal melanomas, but these metastases seldom respond to even the most aggressive regional therapy. Metastases from other nongastrointestinal primary tumors, e.g., lung cancer, are rarely confined to the liver. Relative tumor vascularity would be expected to be an important factor determining tumor responsiveness to blood flow interruption. Primary hepatomas tend to be vascular, and metastastic tumors tend to vary in vascularity (table 7–1). Typically hypervas-cular metastatic tumors are hypernephromas, leiomyosarcomas, carcinoid tumors, islet cell and papillary cell tumors of the pancreas, and transitional cell carcinomas.
Climate Change and Older Americans: State of the Science
Authors: Janet L. Gamble, Bradford J. Hurley, Peter A. Schultz, Wendy S. Jaglom, Nisha Krishnan, Melinda Harris
Journal: Environmental Health Perspectives (2012)

Older adults make up 13% of the U.S. population, but are projected to account for 20% by 2040. Coinciding with this demographic shift, the rate of climate change is accelerating, bringing rising temperatures; increased risk of floods, droughts, and wildfires; stronger tropical storms and hurricanes; rising sea levels; and other climate-related hazards. Older Americans are expected to be located in places that may be relatively more affected by climate change, including coastal zones and large metropolitan areas.The objective of this review is to assess the vulnerability of older Americans to climate change and to identify opportunities for adaptation.We performed an extensive literature survey and summarized key findings related to demographics; climate stressors relevant to older adults; factors contributing to exposure, sensitivity, and adaptive capacity; and adaptation strategies.A range of physiological and socioeconomic factors make older adults especially sensitive to and/or at risk for exposure to heat waves and other extreme weather events (e.g., hurricanes, floods, droughts), poor air quality, and infectious diseases. Climate change may increase the frequency or severity of these events.Older Americans are likely to be especially vulnerable to stressors associated with climate change. Although a growing body of evidence reports the adverse effects of heat on the health of older adults, research gaps remain for other climate-related risks. We need additional study of the vulnerability of older adults and the interplay of vulnerability, resilience, and adaptive responses to projected climate stressors.
Abstract P140: Glycemic Index, Glycemic Load, and Risk of Type 2 Diabetes: Results from 3 Large US Cohorts and an Updated Meta-analysis
Authors: Shilpa N Bhupathiraju, Deidre K Tobias, Vasanti S Malik, An Pan, Adela Hruby, JoAnn E Manson, Walter C Willett, Frank B Hu
Journal: Circulation (2014)

Epidemiologic evidence for the role of glycemic index (GI) and glycemic load (GL) in the prevention of type 2 diabetes (T2D) has been mixed. The American Diabetes Association’s nutrition recommendations for T2D prevention state that there is not sufficient, consistent evidence to conclude that low GL diets reduce T2D risk but acknowledge the role of low GI foods rich in fiber in preventing T2D. Therefore, our objectives were to 1) prospectively examine the association of dietary GI and GL with T2D in 3 US cohorts, and 2) conduct an updated meta-analysis of the previous literature including results from our 3 cohorts. We prospectively followed 74,248 women from the Nurses’ Health Study (1984-2008), 86,484 women from the Nurses’ Health Study II (1991-2009), and 40,525 men from the Health Professionals Follow-up Study (1986-2008) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed every 4 years using a validated questionnaire. During 3,738,507 person-years of follow-up, we documented 14,482 T2D cases. In pooled multivariable analyses, after adjusting for dietary and non-dietary covariates including body mass index, those in the highest quintile of energy-adjusted GI had a 34% higher risk (95% CI: 27-43%) of T2D. Participants in the highest quintile of energy-adjusted GL had a 13% higher risk (95% CI: 5-22%) for T2D. Participants in the highest tertile of GI/GL and lowest tertile of cereal fiber had about a 50% (GI, RR=1.59, 95% CI:1.47-1.73; GL, RR=1.47, 95% CI:1.32-1.63) higher risk for T2D compared to those in the lowest tertile of GI/GL and highest tertile of cereal fiber. In the updated meta-analysis (675,767 participants and 45,570 T2D cases), the summary RRs (95% CIs) comparing the highest versus lowest categories of GI and GL were 1.19 (1.15-1.24) and 1.13 (1.09-1.18), respectively (Figure 1A and 1B). Our findings provide further evidence that a high GI/GL diet is associated with a higher T2D risk. Public health recommendations for T2D prevention should incorporate GI and GL in meal planning.
Abstract P410: Added Sugars Intake, Diet Quality and All-Cause Mortality Among US Adults: Prospective Data from National Health and Nutrition Examination Survey III
Authors: Molly Jung, Robert C Kaplan, Yasmin Mossavar-Rahmani, Shankar Viswanathan, Judith Wylie-Rosett, Jeannette Beasley
Journal: Circulation (2014)

Objectives: To better understand the relationship between added sugars intake and diet quality, and to estimate associations between added sugars intake with all-cause mortality Methods: National Health and Nutrition Examination Survey III data were linked to mortality data (1988-2006), among 13,902 US adults between ages 18-74 yr having energy intake within 500-3500calories for women and 800-4000 calories for men, no history of a heart attack, stroke, or congestive heart failure. Usual intake of added sugars and energy were estimated using the NCI method and categorized into gender-specific quartiles. Diet quality was assessed using the Healthy Eating Index 2005 score (HEI-2005). Associations between added sugars intake and mortality were estimated using Cox proportional hazards regression adjusting for age, race/ethnicity, body mass index (BMI), and usual total energy intake after testing for multiplicative interaction by each of these covariates. Results: Mean intake of added sugar was 17.2 (95% Confidence Interval (CI) 16.8, 17.6) teaspoons (tsp) in women and 25.0 (95% CI 24.4, 25.7) tsp in men. Higher usual intake of added sugars was associated with being younger, a current smoker, and having between 12 and 15 years of education among both men and women. Higher usual intake of added sugars was related to a lower HEI score in women versus a higher HEI score in men (Quartile (Q) 4 for HEI =61.62 versus Q1=64.73 in women, p=0.0002; (Q4=62.71 vs. Q1=60.07 in men, p=0.0209). Higher HEI scores for the grain, fruit, vegetable, meat, and variety components were related to lower intake of added sugars; whereas, the fats, cholesterol, and sodium components of the HEI were related to higher intake of added sugars in men and women. During a median follow-up period of 14 years, a total of 1,889 deaths were recorded. After multivariable adjustment, higher added sugars intake was not associated with increased all-cause mortality (hazard ratio (HR) 95% CI of Q4 vs Q1, 1.08 (0.77, 1.52)). Interpretation: Epidemiological studies suggested that higher sugars intake is associated with an increased risk of obesity and cardiovascular diseases (CVD). These findings indicate higher intake of added sugars is associated with lower diet quality in women, but not men. Added sugars intake was not significantly associated with all-cause mortality in this representative sample of the US population.
Abstract 16701: Conventional Cardiovascular Risk Modifies Clinical Outcomes Among Subjects With Elevated Coronary Artery Calcium Score With and Without Statin Therapy: Post Hoc Analysis From the St Francis Heart Study
Authors: Salman Waheed, Simcha Pollack, Marguerite Roth, Nathaniel Reichek, Alan Guerci, Jie J Cao
Journal: Circulation (2014)

Objective: Coronary artery calcium score (CAC) predicts cardiovascular (CV) risk independent of conventional risk profile. However, it remains unclear how clinical risk profile modifies CV outcomes among subjects with elevated CAC with and without lipid lowering therapy. Methods: We conducted a post hoc analysis of the treatment trial of the St. Francis Heart Study_double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg, vitamin C 1 g, and vitamin E 1,000 U daily, versus matching placebos in 993 asymptomatic individuals with CAC at or above the 80th percentile for age and gender. Primary CV outcomes included non-fatal MI or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. Among the placebo and treatment groups, we further stratified by eligibility for statin therapy based on current AHA guidelines yielding 4 subgroups: treated not eligible (+Rx/-E), placebo not eligible (-Rx/-E), treated eligible (+Rx/+E) and placebo eligible (-Rx/+E). Results: Mean age was 59±6 years. Those eligible were older (61±5 vs. 56±5 years) and more likely to be males (85% vs. 56%) than those not eligible. Median [IQR] CAC was higher in the eligible than not eligible groups (overall, p&lt;0.0001), 199 [112-396] (+Rx/-E), 207 [114-416] (-Rx/-E), 490 [289-791] (+Rx/+E) and 484 [286-837] (-Rx/+E). After a median follow up of 4.8 years, 4.0%, 4.8%, 9.8% and 15.4% had a CV event in +Rx/-E, -Rx/-E, +Rx/+E and -Rx/+E, respectively. After adjusting for CV risk factors and CAC, hazard ratio (95% CI) was 1.1 (0.4-2.9), 3.3 (1.1-9.4) and 4.9 (1.7-14.0) for -Rx/-E, +Rx/+E and -Rx/+E, respectively compared to +Rx/-E. There was a significant interaction between CAC and eligibility for statin therapy for a CV outcome (p=0.05). Conclusion: Among subjects with elevated CAC, those eligible for statin therapy have higher CAC and overall greater risk for a CV outcome than those not eligible. While statin therapy lowers CV risk among those eligible, it does not significantly alter CV risk among those not eligible. There is a significant interaction between CAC and statin therapy eligibility for a CV outcome. Our findings suggest that clinical risk profile remains an important risk modifier for CV outcomes among those with elevated CAC.
Abstract 9956: Effects of Robot-Assisted Therapy Combined With Electrical Stimulation on Motor Control, Motor Impairment, and Daily Function in Stroke Patients
Authors: Ching-yi Wu, Keh-chung Lin, Hsiao-wen Chen, Man-chiao Hsiao
Journal: Circulation (2014)

Introduction: Upper-limb robot-assisted therapy (RT) has been shown to improve motor recovery in chronic stroke patients. Some review studies demonstrated that compared with severely affected patients, moderately affected patients with stroke were more responsive to RT. Neuromuscular electrical stimulation (ES) can effectively induce muscle contraction for stroke patients with severe motor deficit. Thus, ES might serve as an adjuvant intervention for RT to optimize treatment effects. This study aimed to examine the effects of combined robot-assisted therapy with electrical stimulation (RT+ES) on motor control, motor impairment, and daily function. Methods: Twenty-nine patients (mean age: 65 years, mean onset time: 26 months) were randomized into one of the three groups: RT+ES, robot-assisted therapy with sham electrical stimulation (RT+sham ES), and control therapy (CT) groups. Each patient received 90-100 minutes of therapy, 5 days per week for a total of 4 weeks. Outcome measures, representing motor control, motor impairment, and daily function, were kinematic variables, the Fugl-Meyer Assessment (FMA), and the Motor Activity Log (MAL), respectively. Kinematic variables included total displacement (TD), peak velocity (PV), percentage of time where peak velocity occurs (PPV), and movement units (MU). All assessments were performed before and after treatment. Analysis of covariance was used to evaluate training effects. Results: Results showed significant group differences in two kinematic variables (PPV, F = 1.82, p &lt; 0.01; normalized MU, F = 3.41, p = 0.05), proximal subscore of FMA (F = 3.58, p = 0.05) and MAL (amount of use, F = 4.38, p = 0.03; quality of movement, F = 3.71, p = 0.05) in favor of RT+ES. There were no significant group differences for TD, PV, the total FMA score, and the FMA distal subscore. Conclusions: These findings suggest that RT+ES may improve motor control by increasing movement smoothness, reduce motor impairment of proximal part of upper limb, and enhance the performance on daily activities. Further studies could may involve the outcome measures at the participation level such as performance on extended activities of daily living or community reintegration, and evaluate the follow-up effects for RT+ES training.
Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation
Authors: Paramjit K. Khera, Eric P. Smith, Christopher J. Lindsell, Mary Colleen Rogge, Shannon Haggerty, David A. Wagner, Mary B. Palascak, Shilpa Mehta, Jacqueline M. Hibbert, Clinton H. Joiner, Robert S. Franco, Robert M. Cohen
Journal: American Journal of Hematology (2014)

HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC ) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral (15) N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15-20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R(2) = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c.
Community Resources for Rehabilitation of Patients with Chronic Obstructive Pulmonary Diseases and Cor Pulmonale
Authors: THOMAS L. PETTY, BEN V. BRANSCOMB, JOHN F. FARRINGTON, LOUIS J. KETTEL, LARRY A. LINDESMITH
Journal: Circulation (1974)

THE PREVALENCE of chronic obstructive pulmonary diseases (COPD) and the proven capacity of intensive respiratory care to salvage the majority of patients with acute respiratory failure have been well documented.Accumulating evidence now suggests that carefully planned.programs of long-term care incorporating basic prin- ciples of rehabilitation can significantly reduce episodes of acute respiratory failure and can add measurably to the patient's ability to manage his im- pairment in a productive way.Yet despite this knowledge, most communities today remain seriously deficient in the essential medical resources required for the optimal long-term management of patients with COPD.Previous reports of this Commission have dealt with primary prevention of pulmonary heart disease and community resources required for the optimal care of acute respiratory failure.* This statement outlines principles of long-term care and describes the resources needed for such programs.The three statements are complementary and should be studied together.They are intended as a guide for com- munities in developing comprehensive care programs for patients with chronic pulmonary diseases.II. Concepts of Rehabilitation In planning a chronic care program it is important to distinguish between rehabilitation concepts, prin- The preparation of this report was supported under Contract No.