Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and magnitude of classical risk factors for Coronary Heart Disease in a cohort of 4400 Chinese steelworkers over 13.5 years follow-up

Background The incidence and mortality of cardiovascular disease among Orientals are very different than among Caucasians. This study addresses the prevalence and magnitude of classic cardiovascular disease risk factors associated with coronary heart disease (CHD) in an Oriental cohort of at-risk men (blood pressure, total cholesterol, Body Mass Index [BMI] and smoking), compared to Caucasian populations. We also address which blood pressure index (SBP, DBP, mean arterial pressure [MAP] and pulse pressure [PP]) is the best predictor of CHD. Methods and Results A cohort of 5092 male steelworkers (18–74 years old) recruited between 1974–1980 was followed up for an average of 13.5 years. The prevalence of risk factors was lower in Orientals than in Caucasians, except for smoking. The relative risks (RRs) of CHD associated with classic risk factors in this Oriental population were similar to Caucasians, except for blood pressure. The RRs of CHD associated with both SBP and DBP in this Oriental group were higher than in Caucasians; RR of CHD was ∼3 for each 40 mmHg rise of SBP versus ∼2 in Caucasians. SBP was the single best predictor for CHD, followed by MAP, and DBP. The population attributable risk (PAR%) for hypertension (140/90 mmHg) was 42.4. Conclusion Our results would indicate that the lower incidence of CHD in Orientals is at least partly due to the lower prevalence of hypertension, hypercholesterolemia, and obesity. The magnitude of the risk associated with these factors is similar to that in Caucasians, except perhaps for a greater risk associated with hypertension. The most predictive BP index for CHD is SBP. These results are based on indirect comparisons only and should be studied further in prospective multiethnic cohorts. Eur J Cardiovasc Prevention Rehab 11:113–120 © 2004 The European Society of Cardiology.
Mutation of lysine 317 in the D2 subunit of photosystem II alters chloride binding and proton transport.

The role of chloride in photosystem II (PSII) is unclear. Using structural information from PSII and a careful comparison with other chloride-activated enzymes, we proposed a role for chloride at the D2-K317 site in PSII [Pokhrel, R. , et al. (2011) Biochemistry 50, 2725-2734]. To probe the role of chloride at this site, the D2-K317R, D2-K317A, D2-K317Q, and D2-K317E mutations were created in the cyanobacterium Synechocystis sp. PCC 6803. Purified PSII from the mutants was probed with Fourier transform infrared difference spectroscopy, demonstrating that compared to PSII from wild-type Synechocystis, PSII from all four mutants exhibit changes in the conformations of the polypeptide backbone and carboxylate groups. However, D2-K317R PSII exhibits minor changes, whereas D2-K317A, D2-K317Q, and D2-K317E PSII exhibit more substantial changes in polypeptide conformations. Steady-state oxygen-evolution measurements of purified PSII core complexes show that the oxygen-evolution activity of D2-K317A is independent of chloride. This is consistent with the loss of the chloride requirement when the charged K residue is replaced with an uncharged residue that no longer binds to an essential carboxylate (D1-D61) in the absence of chloride, analogous to observations in other chloride-activated enzymes. In contrast, the oxygen-evolution activity of D2-K317R is sensitive to the chloride concentration in the assay buffer; the effective KD for chloride binding is higher in D2-K317R than in wild-type PSII, possibly because of a less optimal binding site in the mutant. The S2 states of wild-type, D2-K317A, and D2-K317R PSII were probed using electron paramagnetic resonance spectroscopy. A g = 2 multiline signal, similar to the wild-type signal, was observed for D2-K317A and D2-K317R. However, a g = 4 signal was also observed for D2-K317R. Measurements of flash-dependent O2 yields showed that D2-K317A and D2-K317R have a higher miss factor than wild-type PSII. The oxygen-release kinetics of D2-K317A and D2-K317R were slower than those of the wild type, in the following order: D2-K317A < D2-K317R < wild type. These results collectively suggest that proton transfer is inefficient in D2-K317A and D2-K317R, thereby giving rise to a higher miss factor and slower oxygen-release kinetics.
Hypertension and sleep apnoea

SUMMARY Epidemiological data indicate a link between sleep‐disordered breathing and elevation of arterial pressure. Previous studies suggest increased activity of the sympathetic nervous system in patients with sleep apnoea. The response of muscle sympathetic nerve activity was further investigated in normal, awake subjects following exposure to 20 minutes of asphyxia. Sympathetic nerve traffic increased during exposure and remained elevated even after the return to room air breathing. These findings raise the possibility that this sustained elevation of sympathetic nerve traffic could play a role in the development of daytime hypertension in patients with sleep‐disordered breathing.
Shock response of a model structured nanofoam of Cu

Using large-scale molecular dynamics simulations, we investigate shock response of a model Cu nanofoam with cylindrical voids and a high initial porosity (50% theoretical density), including elastic and plastic deformation, Hugoniot states, shock-induced melting, partial or complete void collapse, nanojetting, and hotspot formation. The elastic-plastic and overtaking shocks are observed at different shock strengths. The simulated Hugoniot states can be described with a modified, power-law P−α (pressure–porosity) model, and agree with shock experiments on Cu powders, as well as the compacted Hugoniot predicted with the Gruneisen equation of state. Shock-induced melting shows no clear signs of bulk premelting or superheating. Voids collapse via plastic flow nucleated from voids, and the exact processes are shock strength dependent. With increasing shock strengths, void collapse transits from the “geometrical” mode (collapse of a void is dominated by crystallography and void geometry and can be different from that of one another) to “hydrodynamic” mode (collapse of a void is similar to one another); the collapse may be achieved predominantly by flow along the {111} slip planes, by way of alternating compression and tension zones, by means of transverse flows, via forward and transverse flows, or through forward nanojetting. The internal jetting induces pronounced shock front roughening, leading to internal hotspot formation and sizable high speed jets on atomically flat free surfaces.
Adverse drug events Adverse-drug-event rates for high-cost and high-use drugs in the intensive care unit

SANDRA KANE-GILL, PHARM.D. , M.SC., is Assistant Professor, Department of Pharmacy and Therapeutics, Center for Pharmacoinformatics and Outcomes Research, School of Pharmacy, University of Pittsburgh (UP), Pittsburgh, PA. RHONDA S. REA, PHARM.D. , is Assistant Professor, Department of Pharmacy and Therapeutics, School of Pharmacy, UP, and Critical Care Specialist, Medical Intensive Care Unit, University of Pittsburgh Medical Center (UPMC), Pittsburgh. MARGARET M. VERRICO, B.S., is Assistant Professor, Department of Pharmacy and Therapeutics, School of Pharmacy, UP, and Drug Information Pharmacist, UP Drug Information Center, UPMC. ROBERT J. WEBER, M.S., FASHP, is Associate Professor and Chairman, Department of Pharmacy and Therapeutics, School of Pharmacy, UP, and Chief Pharmacy Officer, UPMC. Address correspondence to Dr. Kane-Gill at the Center for Pharmacoinformatics and Outcomes Research, University of Pittsburgh, 918 Salk Hall, 3501 Terrace Street, Pittsburgh, PA 15261 (kanesl@upmc.edu). Vince Oriolo, Anthony Lacava, and Melissa Saul are acknowledged for obtaining the data necessary for this project. Teresa McKaveney is acknowledged for her critical review of the manuscript. Funded in part by the American Society of Health-System Pharmacists Research and Education Foundation, Bethesda, MD.
Water uptake in stimulated cat skeletal muscle.

Isolated vasodilated cat hindlimb skeletal muscles were perfused at constant flow and stimulated at 4 Hz for 2-4 min in three studies. Water uptake rates were measured gravimetrically or calculated from venous protein concentration changes. Venous plasma sodium, potassium, chloride, and osmolality were also measured. Maximum water uptake rates averaged 1.8 +/- 0.2 (SE) ml.min-1 x 100 g-1, reaching twice that in some experiments. Water uptake continued after stimulation had ceased. Constant-flow perfusion maintained a constant capillary pressure that was corroborated by measurements of arterial and venous perfusate pressures. Water uptake rate was not influenced by hematocrit but was highly correlated with plasma flow rate. The evidence strongly suggests that small-molecule osmotic pressure was the primary pressure causing the transcapillary water flux. Venous plasma sodium and chloride concentrations increased almost as much as protein (108 and 87% of the protein increase, respectively), as would be expected when water fluxes are driven by small-molecule osmotic pressure. Peak potassium efflux averaged 36 +/- 3 mu eq.min-1 x 100 g-1, but potassium did not contribute significantly to the osmotic gradient.
Dynamics of natural immunity caused by subclinical infections, case study on Haemophilus influenzae type b (Hib)

Natural immunity to Haemophilus influenzae type b (Hib) is based primarily on antibodies that are thought to develop in response to subclinical infections. Wide use of conjugated Hib vaccines could lead to decreases in circulating Hib bacteria, thereby diminishing antibody levels in the unvaccinated. We applied a statistical model to estimate the duration of natural immunity to Hib under different forces of infection. Prior to the introduction of conjugated Hib vaccines, new Hib infections were estimated to occur once in 4 years and the antibody concentration to stabilize at a level around 1 μg/ml. In the absence of new stimuli, i.e. infection, 57% of the unvaccinated population would become susceptible to invasive disease (antibody levels < 0·15 μg/ml) in 10 years. Due to an interaction between the force of infection and the duration of immunity, in some situations numbers of invasive infections could increase in unvaccinated cohorts. This theoretical scenario has yet to be observed in practice.
Endotoxin‐Induced Regional Circulatory Changes in the Unanesthetized Monkey

Endotoxin in eight unanesthetized monkeys produced a small decrease in cardiac output, a marked fall in blood pressure, and a decrease in total peripheral vascular resistance. The distribution of cardiac output was measured by injecting nuclide-labeled radioactive microspheres (50μ in diameter) into the left ventricle, and blood flow and vascular resistance were calculated for each organ. All vascular beds except that of the spleen reacted with variable degrees of vasodilation, and the most pronounced decreases in resistance were observed in the coronary, gastrointestinal, and adrenal vasculature. Cerebral flow was reduced, but flow was maintained in the brain stem and cerebellum. In contrast to studies in other species, both the gastrointestinal tract and the kidneys showed vasodilation and no significant decrease in flow during the early phase of endotoxemia. There is some similar evidence in humans of decreased total systemic peripheral resistance without abnormal myocardial function or pooling of blood during the early phase of endotoxemia. The acute regional circulatory changes we have found appear to indicate that endotoxin either directly or through secondary biochemical reactions initiates and maintains a generalized (except for the spleen) vasodilation that reflex compensatory mechanisms cannot overcome. This vasodilation is particularly critical in preventing maintenance of adequate blood flow to the cerebral hemispheres.
Cognitive deficits in children with gelastic seizures and hypothalamic hamartoma

Objective: To characterize the cognitive deficits in children with gelastic seizures and hypothalamic hamartoma and investigate the relationship of seizure severity to cognitive abilities. Methods: Eight children with gelastic seizures and hypothalamic hamartoma completed a neuropsychological battery of standardized and age-normed tests, including the Woodcock–Johnson Psycho-Educational Battery–Revised: Tests of Cognitive Ability, Peabody Picture Vocabulary Test-III, and initial-letter word fluency measure. Results: All children displayed cognitive deficits, ranging from mild to severe. Gelastic/complex partial seizure severity was correlated with broad cognitive ability standard scores (r = −0.79; r2 = 0.63; (F[1,6] = 10.28; p = 0.018]. Frequency of gelastic/complex partial seizures was also correlated with broad cognitive ability standard scores (r = −0.72; r2 = 0.52; F[1,6] = 6.44; p = 0.044). Significant intracognitive standard score differences were found, with relative weaknesses in long-term retrieval (mean = 64.1; SD = 13.3) and processing speed (mean = 67.7; SD = 21.6) and a relative strength in visual processing (mean = 97.6; SD = 12.8). Performance in visual processing differed from performance in long-term retrieval (p = 0.009) and processing speed (p = 0.029). Conclusion: These findings are consistent with cognitive functions and affective/emotional states associated with conduction pathways of the hypothalamus involving cortical association areas and amygdala and hippocampal formation. These abnormalities can account for the prominent deficit found in integrating information in the processing of memories.
GGDEF and EAL domains inversely regulate cyclic di‐GMP levels and transition from sessility to motility

Cyclic nucleotides represent second messenger molecules in all kingdoms of life. In bacteria, mass sequencing of genomes detected the highly abundant protein domains GGDEF and EAL. We show here that the GGDEF and EAL domains are involved in the turnover of cyclic‐di‐GMP (c‐di‐GMP) in vivo whereby the GGDEF domain stimulates c‐di‐GMP production and the EAL domain c‐di‐GMP degradation. Thus, most probably, GGDEF domains function as c‐di‐GMP cyclase and EAL domains as phosphdiesterase. We further show that, in the pathogenic organism Salmonella enterica serovar Typhimurium, the nosocomial pathogen Pseudomonas aeruginosa and the commensal species Escherichia coli, GGDEF and EAL domains mediate similar phenotypic changes related to the transition between sessility and motility. Thus, the data suggest that c‐di‐GMP is a novel global second messenger in bacteria the metabolism of which is controlled by GGDEF and EAL domain proteins.
HDL cholesterol predicts coronary heart disease mortality in older persons.

OBJECTIVES To examine the relationship of total cholesterol and high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) mortality and with occurrence of new CHD events in persons aged 71 years and older. DESIGN Prospective cohort study with a median of 4.4 years of follow-up. SETTING East Boston, Mass; New Haven, Conn; and Iowa and Washington counties, Iowa. PARTICIPANTS A total of 2527 women and 1377 men who completed an interview, had serum lipid determinations, and survived at least 1 year. New CHD events were evaluated in persons with no CHD history or hospitalization. MAIN OUTCOME MEASURES Death due to CHD (ICD-9 codes 410 through 414 as underlying cause of death); new occurrence of CHD events (fatal CHD or hospitalization with CHD [ICD-9 codes 410 through 414]). RESULTS After adjustment for established CHD risk factors, the relative risk (RR) of death due to CHD for those with low HDL-C (< 0.90 mmol/L [< 35 mg/dL]) compared with the reference group (HDL-C > or = 1.55 mmol/L [> or = 60 mg/dL]) was 2.5 (95% confidence interval [CI], 1.6 to 4.0). Elevated risk was present in subgroups aged 71 through 80 years (RR, 4.1; 95% CI, 1.9 to 8.8) and over 80 years (RR, 1.8; 95% CI, 0.99 to 3.4), and in men and women. Low HDL-C predicted an increased risk of occurrence of new CHD events (RR, 1.4; 95% CI, 1.1 to 2.0), with similar but nonsignificant results in subgroups of men and women. Total cholesterol was less consistently associated with CHD mortality than HDL-C. When we compared individuals with total cholesterol of at least 6.20 mmol/L (240 mg/dL) with the reference group with total cholesterol of 4.16 to 5.19 mmol/L (161 to 199 mg/dL), a significant risk of CHD mortality was seen for women (RR 1.8; 95% CI, 1.03 to 3.0) but not for men (RR, 1.0; 95% CI, 0.5 to 2.0). In the total population, for each 1-unit increase in the total cholesterol/HDL-C ratio there was a 17% increase in the risk of CHD death that was statistically significant. CONCLUSIONS Low HDL-C predicts CHD mortality and occurrence of new CHD events in persons older than 70 years. Elevated total cholesterol was not found to be associated with CHD mortality in older men, but may be a risk factor for CHD in older women.
Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality.

Demographic information, risk factors, therapy, and outcome for all patients who had candidemia at Barnes Hospital, St. Louis, between 1 September 1988 and 1 September 1989 were retrospectively reviewed. One hundred six candidemic patients were identified, representing 0.5% of all medical and surgical discharges and 0.33% of total patient discharges. These percentages represent a 20-fold increase in the incidence of candidemia at our hospital in comparison with that during 1976-1979. Candida albicans was the most frequently isolated species (63%), followed by Candida tropicalis (17%), Candida glabrata (13%), Candida parapsilosis (6.5%), and Candida krusei (0.9%). Overall mortality was 57%, and 14 (23%) of 60 deaths occurred within 48 hours of the detection of candidemia. Mortality was associated with higher APACHE II scores (25 for nonsurvivors vs. 16 for survivors; P = .0001), the presence of a rapidly fatal underlying illness (P = .0009), and sustained positivity of blood cultures (P = .02). In cases of sustained candidemia, the isolation of non-albicans Candida species also correlated with increased mortality (8 of 8 vs. 10 of 21; P = .005). Thirty candidemic patients (28%) did not receive any antifungal therapy, and 19 (63%) of these untreated patients died. Eleven untreated patients (37%) survived without sequelae. There has been a marked increase in the incidence of candidemia in our institution that is associated with a high overall mortality. Candidemia lasting less than 24 hours was associated with a lower mortality than was that of longer duration. Severity of illness and duration of candidemia should be used as stratifying factors in prospective studies to determine optimum therapy.
Differential regulation of the zinc finger genes Krox‐20 and Krox‐24 (Egr‐1) suggests antagonistic roles in Schwann cells

Krox‐20 and Krox‐24 (Egr‐1) encode closely related zinc finger transcription factors, which interact with the same DNA target sequences. Krox‐20 is required for myelination in the peripheral nervous system. Using lacZ knock‐in mutant mouse lines as well as immunohistochemical analyses, we have studied the expression of Krox‐20 and Krox‐24 in the Schwann cell lineage during normal development and following nerve lesion in the mouse and in human neuropathies. During embryogenesis, the two genes are expressed in a successive and mutually exclusive manner, Krox‐24 being restricted to Schwann cell precursors and Krox‐20 to mature Schwann cells. At birth, Krox‐24 is reactivated and the two genes are coexpressed. In the adult, Krox‐20 is expressed in myelinating cells, while Krox‐24 is restricted to nonmyelinating cells. Following nerve lesion, Krox‐24 is strongly induced in Schwann cells, reinforcing the link between its expression and the nonmyelinating and/or proliferative state, whereas Krox‐20 is downregulated. These data are consistent with Krox‐20 and Krox‐24 playing antagonistic roles during the development of the Schwann cell lineage. In particular, their balance of expression might participate in the choice between myelinating and nonmyelinating pathways. J. Neurosci. Res. 50:702–712, 1997. © 1997 Wiley‐Liss, Inc.
Implications of surface temperatures in the diagnosis of breast cancer.

ONE OF THE IMPORTANT biological characteristics of. malignant tumours is the increased rate of growth as compared to that of the surrounding or host tissue. The malignant propensities are directly related to the speed of cell division. This in turn is reflected by accelerated local metabolism which is adequately supported by increased blood and lymphatic vascularity. These biological alterations can be readily detected by estimating temperature changes in the tumour or its immediate environment. Heat energy is transferred by the process of convection, conduction and radiation. It is possible to record, with a fair degree of accuracy, the transfer by the latter two methods. The recording of heat energy by conduction from the skin can be performed by the calculation of the electromotive force created at the juncture of two dissimilar metals such as platinum and rhodium. Such a device is commonly called a thermocouple. This instrument appears to be a useful diagnostic tool where breast cancer is suspected, as the technique can easily be applied to the skin over the tumour, or in the case of a deep-seated neoplasm, the ipsilateral areola. Heretofore considerable investigative work has been done in determining the possibilities of infra-red phlebograms. Massopust' and coworkers have published a series of such observations. The technical limitations of this approach are apparent when one realizes that the most sensitive infra-red photographic emulsions extend to only 11,000 Angstrom units, and in this part of the spectrum the intensity of radiant energy is extremely small. Another method which holds some promise is the use of the Baird Evaporograph, an instrument designed to give a direct thermal picture on a very thin oil film. The main principle employed in this apparatus is the differential evaporation of an oil film on a transparent membrane which can be observed or photographed in black and white or colour. In its present state of development, the Evaporograph has a high resolution for objects having sudden or abrupt temperature changes, however slight (such as blacked-out
Novel therapy for renal protection

Purpose of review Acute kidney injury (AKI) is a common and serious complication that significantly increases morbidity, mortality, and cost of care after surgery. In this article, we review recent studies that deal with strategies for renal protection and the prevention of AKI after surgery. Recent findings A prerequisite for any prophylactic intervention is the identification of patients at risk for AKI or those with acute kidney damage before kidney function deteriorates. In this context, new biomarkers can help to detect cellular injury early. This way, a window for interventions can be opened. Several studies demonstrated the tissue-protective effect of remote ischemic preconditioning in various organs. There is clear evidence that use of balanced crystalloid fluids and the avoidance of hyperchloremic solutions for infusion therapy can reduce the incidence of AKI. Preliminary data show a protective effect if dexmedetomidine is used as a sedative agent following cardiac surgery. The most important intervention with proven efficacy to protect from AKI is aggressive hemodynamic stabilization. Summary Early identification of patients at risk for AKI is crucial to apply any protective intervention. An improved perioperative management is required to prevent AKI. Although pharmacological therapies aiming to protect AKI are under evaluation, hemodynamic optimization and avoidance of nephrotoxic drugs are critical for perioperative patient.