Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation between cholesterol esterification, MDR1 gene expression and rate of cell proliferation in CEM and MOLT4 cell lines

Abstract. A positive correlation between cholesterol esterification and growth rate potential was previously found in our laboratory during the growth of CEM and MOLT4 lymphoblastic cells. In the current study, we investigated whether the rates of cholesterol esters synthesis correlate with changes of acyl‐CoAcholesterol acyltransferase (ACAT) mRNA levels and of other genes implied in cholesterol biosynthesis and uptake, such as 3‐hydroxy‐3‐methylglutaryl‐CoA (HMGCoA) reductase and low density lipoprotein (LDL) receptor. The results showed that the more rapid growing CEM cells had lower levels of expression of HMGCoA‐reductase and LDL receptors compared to MOLT4. By contrast, ACAT mRNA levels were higher in CEM cells, further supporting the concept of a possible involvement of cholesterol esters in the regulation of cell growth and division. In this study, high levels of cholesterol esterification and of expression of ACAT gene were also associated with a markedly increased expression of multidrug resistance (MDR1) gene, suggesting that MDR1 activity might contribute to regulate the rate of cell growth and division by modulating intracellular cholesterol ester levels.
Addressing ‘the elephant on the table’: barriers to end of life care conversations in heart failure – a literature review and narrative synthesis

Purpose of reviewHeart failure is a life-limiting illness, but with great uncertainty over its prognosis. Policy increasingly states the importance of discussions about end of life care between patients and their clinicians. This study reviews the extent to which there is evidence that these conversations occur for heart failure patients in practice. Recent findingsAlthough several opinion pieces and guidelines on this topic have emerged in recent years, little new empirical data have been published. Papers publishing empirical data since 2005 and other literature suggest that these conversations rarely occur. Many clinicians feel uncomfortable or lack confidence; and there is uncertainty whether patients want such discussions. Barriers and facilitators for discussions with heart failure are identified, regarding the nature of the disease, resource constraints and attitudes. The consequence is that disempowered patients rarely have such discussions: the ‘elephant on the table’ is rarely addressed. SummaryThe wide range of barriers identified all hinder conversations about the end of life with heart failure patients. Individual patient preferences for the timing and content of such conversations must be respected, including the wish of some not to have such conversations at all.
Adverse cardiac outcomes after noncardiac surgery in patients with prior percutaneous transluminal coronary angioplasty.

UNLABELLED In this retrospective cohort study, we compared adverse cardiac outcomes after noncardiac surgery among patients with prior percutaneous transluminal coronary angioplasty (PTCA), patients with nonrevascularized coronary artery disease (CAD), and normal controls. Inpatient hospital discharge abstracts from all nonfederal acute care hospitals in Washington State linked to death certificates were evaluated. Patients > or =45 yr old with prior PTCA who underwent noncardiac surgery from 1987 to 1993 were matched by age, sex, surgery type, and discharge year to 686 patients with CAD and to 2155 normal controls (no CAD). We compared risk for adverse cardiac outcomes (death, myocardial infarction, angina, congestive heart failure, malignant dysrhythmia, cardiogenic shock, coronary artery bypass graft, or PTCA) within 30 days. Patients with PTCA had twice the risk of adverse cardiac outcome as normal controls (odds ratio [OR] 1.98; P < 0.001), with a higher risk of angina (OR 7.84), congestive heart failure (OR 2.06), and myocardial infarction (OR 3.86) but a lower risk of death (OR 0.46; P < 0.001). Patients with PTCA had half the risk of adverse cardiac outcome as patients with CAD (OR 0.50; P < 0.001), including less risk of angina (OR 0.51) and congestive heart failure (OR 0.40; P < 0.001), but no difference in myocardial infarction (P = 0.304) or death (P = 0.436). No difference was found between 142 patients with recent PTCA (< or =90 days before noncardiac surgery) matched to patients with CAD (OR 0.90; P = 0.396). Patients revascularized by PTCA >90 days before noncardiac surgery seem to have a lower risk of poor outcome than nonrevascularized patients, although not as low as normal controls. For recent PTCA patients, the lack of difference compared with CAD patient outcomes requires a larger sample size for verification. Present findings do not lend support to a role for prophylactic PTCA to improve noncardiac surgery outcomes. This investigation did not control for CAD severity, medical management, or comorbidities. Study of these factors is needed before the clinical implications of PTCA for noncardiac surgical risk can be completely assessed. IMPLICATIONS Hospital records showed patients with prior percutaneous transluminal coronary angioplasty were twice as likely as healthy patients to have an adverse cardiac outcome after noncardiac surgery, although their risk was reduced by half compared with patients with untreated coronary artery disease. Further study of the role of percutaneous transluminal coronary angioplasty in modulating noncardiac surgery risk is needed.
Rising Death Rates among Polish Men

All-causes mortality rates turned sharply upward for Polish men around 1972. Increases of 25 percent or greater were recorded for all five-year age groups between 40 and 59 years. Other indices, including infant mortality and death rates for women, either continued to improve or did not change. The primary causes accounting for this upturn appear to be cardiovascular diseases and cancer of the lung. The epidemiological pattern in Poland reflects in part the long-term trend for consumption of food, alcohol, and tobacco to approximate that found in Western industrialized countries. The role of more generalized social changes associated with Poland's rapid industrialization cannot be evaluated directly. Although it is still too early to see the effect of the social crisis of the last two years, economic disruption and shortages are not the main factors accounting for the upturn in Polish mortality through 1980. In fact, the success of the Polish economic strategy appears to be the underlying social cause.
Presence of immunoglobulins, C3 and cytolytic C5b‐9 complement components on the surface of erythrocytes from patients with β‐thalassaemia/HbE disease

The occurrence of IgG, IgM, IgA, C3 and C5b‐9 complement complexes on erythrocytes from 43 patients with β‐thalassaemia HbE disease was investigated. Indirect immunoradiometric assays using radioiodinated protein A were employed to quantify the individual components. We confirmed that circulating erythrocytes from thalassaemic patients contained elevated amounts of IgG, and small but significant amounts of C3. In addition, small but significant amounts of C5b‐9 were detected. Levels of cell‐bound IgG, C3 and C5b‐9 were higher in splenectomized versus non‐splenectomized patients. The presence of C5b‐9 on circulating cells from five splenectomized patients was confirmed by an ELISA employing a monoclonal antibody specific for a C5b‐9 neoantigen. When C5b‐9 positive cells from two patients were solubilized with detergent and subjected to sucrose density gradient centrifugation, the terminal complexes sedimented as 25–40S macromolecules, thus behaving as membrane C5b‐9 complexes. The presence of C8 and C9 in these high molecular weight fractions was directly demonstrated by Western blotting. These results constitute the first demonstration that circulating diseased erythrocytes may carry low numbers of potentially cytolytic C5b‐9 complement complexes which may be partly responsible for the known ionic disturbances found in thalassaemic cells. Both bound C3 and C5b‐9 could promote removal of diseased cells in the reticuloendothelial system.
The effects of aging on the working memory processes of multimodal information

ABSTRACT Normal aging is associated with deficits in working memory processes. However, the majority of research has focused on storage or inhibitory processes using unimodal paradigms, without addressing their relationships using different sensory modalities. Hence, we pursued two objectives. First, was to examine the effects of aging on storage and inhibitory processes. Second, was to evaluate aging effects on multisensory integration of visual and auditory stimuli. To this end, young and older participants performed a multimodal task for visual and auditory pairs of stimuli with increasing memory load at encoding and interference during retention. Our results showed an age-related increased vulnerability to interrupting and distracting interference reflecting inhibitory deficits related to the off-line reactivation and on-line suppression of relevant and irrelevant information, respectively. Storage capacity was impaired with increasing task demands in both age groups. Additionally, older adults showed a deficit in multisensory integration, with poorer performance for new visual compared to new auditory information.
Inhibition of T‐Type and L‐Type Calcium Channels by Mibefradil: Physiologic and Pharmacologic Bases of Cardiovascular Effects

&NA; Ca2+ channel antagonists of the dihydropyridine, benzothiazepine, and phenylalkylamine classes have selective effects on L‐type versus T‐type Ca2+ channels. In contrast, mibefradil was reported to be more selective for T‐type channels. We used the whole‐cell patch‐clamp technique to investigate the effects of mibefradil on T‐type and L‐type Ca2+ currents (ICaT and ICaL) recorded at physiologic extracellular Ca2+ in different cardiac cell types. At a stimulation rate of 0.1 Hz, mibefradil blocked ICaT evoked from negative holding potentials (HPs) (‐100 mV to ‐80 mV) with an IC50 of 0.1 &mgr;M in rat atrial cells. This concentration had no effect on ICaL in rat ventricular cells (IC50: ˜3 &mgr;M). However, block of ICaL was enhanced when the HP was depolarized to ‐50 mV (IC50: ˜0.1 &mgr;M). Besides a resting block, mibefradil displayed voltage‐ and use‐dependent effects on both ICaT and ICaL. In addition, inhibition was enhanced by increasing the duration of the stepdepolarizations. Similar effects were observed in human atrial and rabbit sinoatrial cells. In conclusion, mibefradil combines the voltage‐ and use‐dependent effects of dihydropyridines and benzothiazepines on ICaL. Inhibition of ICaL, which has probably been underestimated before, may contribute to most of the cardiovascular effects of mibefradil.
Short-Wavelength Automated Perimetry in Type I Diabetic Patients without Retinal Involvement: A Test Modification to Decrease Test Duration

Purpose To compare short-wavelength automated perimetry (SWAP) between type I diabetic patients without clinical posterior segment involvement and nondiabetic control subjects. Methods Forty eyes of diabetic patients without obvious posterior segment involvement and 34 eyes of the nondiabetic control group were included in the study. A complete set of ophthalmic examination was followed by SWAP perimetry in all subjects. Short-wavelength automated perimetry results were compared between the 2 groups. In addition, as a modification to SWAP, the data of the central 16 points were omitted and the resulting data of the remaining 60 points (corrected data) were compared between the 2 groups. Results Mean deviation in the diabetic patients (group I) was −6.51 dB and in the control group (group II) −3.0 dB; the difference was statistically significant. Mean corrected sensitivity in group I was 19.79 dB and in group II 22.37 dB. Mean corrected total deviation in group I was −6.67 and in group II −3.22. Both differences were highly statistically significant. The mean corrected pattern deviation in group I was −3.29 and in group II −3.04, which was not a statistically significant difference. Conclusions Short-wave automated perimetry abnormalities precede diabetic retinopathy in type I diabetic patients and omission of central 16 points does not compromise test results in this situation.
Metabolism of the Intervertebral Disc: Effects of Low Levels of Oxygen, Glucose, and pH on Rates of Energy Metabolism of Bovine Nucleus Pulposus Cells

Study Design. In vitro measurements of metabolic rates of isolated bovine nucleus pulposus cells at varying levels of oxygen, glucose, and pH. Objectives. To obtain quantitative information on the interactions between oxygen and glucose concentrations and pH, and the rates of oxygen and glucose consumption and lactic acid production, for disc nucleus cells. Summary of Background Data. Disc cells depend on diffusion from blood vessels at the disc margins for supply of nutrients. Loss of supply is thought to lead to disc degeneration, but how loss of supply affects nutrient concentrations in the disc is not known; nutrient concentrations within discs can normally only be calculated, because concentration measurements are invasive. However, realistic predictions cannot be made until there are data from measurements of metabolic rates at conditions found in the disc in vivo, i.e., at low levels of oxygen, glucose, and pH. Methods. A metabolism chamber was designed to allow simultaneous recording of oxygen and glucose concentrations and of pH. These concentrations were measured electrochemically with custom-built glucose and oxygen sensors; lactic acid was measured biochemically. Bovine nucleus pulposus cells were isolated and inserted into the chamber, and simultaneous rates of oxygen and glucose consumption and of lactic acid production were measured over a range of glucose, oxygen, and pH levels. Results. There were strong interactions between rates of metabolism and oxygen consumption and pH. At atmospheric oxygen levels, oxygen consumption rate at pH 6.2 was 32% of that at pH 7.4. The rate fell by 60% as oxygen concentration was decreased from 21 to 5% at pH 7.4, but only by 20% at pH 6.2. Similar interactions were seen for lactic acid production and glucose consumption rates; we found that glycolysis rates fell at low oxygen and glucose concentrations and low pH. Equations were derived that satisfactorily predict the effect of nutrient and metabolite concentrations on rates of lactic acid production rate and oxygen consumption. Conclusions. Disc cell metabolism in air and at pH 7.4 differs markedly from that found in the disc nucleus invivo, where low levels of oxygen, glucose, and pH all coexist.
Impact of self-financed rotavirus vaccines on hospital stays and costs in Spain after a 3-year introductory period

SUMMARY Vaccination has reduced rotavirus hospitalizations by 25% in European regions with low–moderate vaccine availability. We aimed to quantify the reduction in hospital costs after the longest period in which Rotarix® and Rotateq® were simultaneously commercially available in Spain. Cases, length of stay (LOS), and diagnosis-related groups (DRGs) were retrieved from the Minimum Basic Data Set. Healthcare expenditure was estimated through the cost accounting system Gescot®. DRGs were clustered: I, non-bacterial gastroenteritis with complications; II, without complications; III, requiring surgical/other procedures or neonatal cases (highest DRG weights). Comparisons between pre (2003–2005)- and post-vaccine (2007–2009) hospital stays and costs by DRG group were made. Rotaviruses were the most common agents of specific-coded gastroenteritis (N = 1657/5012). LOS and extended LOS of rotaviruses fell significantly in 2007–2009 (β-coefficient = −0·43, 95% confidence intervals (95% CI) −0·68 to −0·17; and odds ratio 0·62, 95% CI 0·50–0·76, respectively). Overall, costs attributable to rotavirus hospitalizations fell approximately €244 per patient (95% CI −365 to −123); the decrease in DRG group III was €2269 per patient (95% CI −4098 to −380). We concluded modest savings in hospital costs, largely attributable to cases with higher DRG weights, and a faster recovery. A universal rotavirus vaccination program deserves being re-evaluated, regarding its potential high impact on both at-risk children and societal costs.
Antiviral activities of extracts and selected pure constituents of Ocimum basilicum

1. Ocimum basilicum (OB), also known as sweet basil, is a well known medicinal herb in traditional Chinese medicine preparations. In the present study, extracts and purified components of OB were used to identify possible antiviral activities against DNA viruses (herpes viruses (HSV), adenoviruses (ADV) and hepatitis B virus) and RNA viruses (coxsackievirus B1 (CVB1) and enterovirus 71 (EV71)).
Classification and Characterization of Hereditary Types 2A, 2B, 2C, 2D, 2E, 2M, 2N, and 2U (Unclassifiable) von Willebrand Disease

All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.
Scholarly productivity of united states academic cardiothoracic anesthesiologists: influence of fellowship accreditation and transesophageal echocardiographic credentials on h-index and other citation bibliometrics.

OBJECTIVE The h-index allows the evaluation of scholarly output in academics, but this bibliometric statistic has not been applied extensively to measure productivity in anesthesiology. The authors tested the hypothesis that the h-index is dependent on academic rank, American College of Graduate Medical Education (ACGME) accreditation of the training program, and National Board of Echocardiography credentials in perioperative transesophageal echocardiography (TEE) in United States academic cardiothoracic anesthesiologists. DESIGN Observational. SETTING Internet analysis. PARTICIPANTS United States academic cardiothoracic anesthesiologists. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Faculty members from 30 randomly selected fellowship programs with or without accreditation were identified using the Society of Cardiovascular Anesthesiologists web site. The status of each faculty member's credentials in perioperative TEE was defined using the "verify certification" function on the National Board of Echocardiography web site. Publications, citations, citations/publication, and the h-index for each faculty member were obtained using Scopus. Two hundred fifty-nine cardiothoracic anesthesiologists (204 men and 55 women) were identified (8 instructors [3%], 123 assistant professors [48%], 56 associate professors [22%], 63 professors [24%], and 9 chairpersons [3%]). The average cardiothoracic anesthesiologist had an h-index of 6 ± 7 with 28 ± 46 publications, 499 ± 988 total citations, and 13 ± 18 citations per publication. The h-index increased significantly (p < 0.05) among ranks (instructors [1 ± 1], assistant professors [3 ± 3], associate professors [7 ± 5], professors [12 ± 8], and chairpersons [18 ± 13]). Significant differences in the number of publications and total citations also were observed among ranks. Differences in the h-index among ranks were observed regardless of program accreditation status or transesophageal echocardiographic credentials. Faculty members working in American College of Graduate Medical Education-accredited programs had more publications and citations and higher h-indices than their counterparts in programs that were not accredited. Except for program directors, the scholarly output of academic cardiothoracic anesthesiologists with or without transesophageal echocardiographic credentials was similar within each academic rank. CONCLUSIONS The results show that the h-index increases progressively with academic rank and is dependent on fellowship program accreditation status but not transesophageal echocardiographic credentials in United States academic cardiothoracic anesthesiologists.
On the delivery of small interfering RNAs into mammalian cells

RNA interference is becoming the technique of choice for analysing gene function and drug target validation. In this process, sequence-specific gene inhibition is initiated by small RNA duplexes, known as small interfering RNAs (siRNAs). The possibility that exogenously delivered siRNAs or endogenously expressed hairpin siRNAs can cause the destruction of specific target mRNA in vitro and in animal models has been demonstrated. However, the key challenges for the development of siRNAs as human therapeutics is largely dependent on the development of suitable delivery agents and improved siRNA specificity. This review highlights recent advances in siRNA delivery, as well as challenging problems related to immune stimulation.
Bioengineered Dental Tissues Grown in the Rat Jaw

Our long-term objective is to develop methods to form, in the jaw, bioengineered replacement teeth that exhibit physical properties and functions similar to those of natural teeth. Our results show that cultured rat tooth bud cells, seeded onto biodegradable scaffolds, implanted into the jaws of adult rat hosts and grown for 12 weeks, formed small, organized, bioengineered tooth crowns, containing dentin, enamel, pulp, and periodontal ligament tissues, similar to identical cell-seeded scaffolds implanted and grown in the omentum. Radiographic, histological, and immunohistochemical analyses showed that bioengineered teeth consisted of organized dentin, enamel, and pulp tissues. This study advances practical applications for dental tissue engineering by demonstrating that bioengineered tooth tissues can be regenerated at the site of previously lost teeth, and supports the use of tissue engineering strategies in humans, to regenerate previously lost and/or missing teeth. The results presented in this report support the feasibility of bioengineered replacement tooth formation in the jaw.