Miracle-dz/UniFAR-FTUs huggingface dataset:
Can [15O]Water Be Used to Evaluate Drugs?

There is an extensive literature supporting the use of rCBF as a surrogate marker of local neuronal activity. This provides a strong physiologic rationale for using PET measurements of rCBF to study the effects of drugs acting on the brain. The ability to perform multiple brief measurements of rCBF with [15O]water in a single study session makes possible a wide variety of experimental designs. Numerous investigators have successfully applied the method to study a wide variety of centrally acting drugs. In summary, then, the answer to the question, "Can [15O]water be used to evaluate drugs? " is a definitive yes.
Effect of a high-fat diet on the hepatic expression of nuclear receptors and their target genes: relevance to drug disposition

More than 1·4 billion individuals are overweight or obese worldwide. While complications often require therapeutic intervention, data regarding the impact of obesity on drug disposition are scarce. As the influence of diet-induced obesity on drug transport and metabolic pathways is currently unclear, the objective of the present study was to investigate the effect of high fat feeding for 13 weeks in female Sprague–Dawley rats on the hepatic expression of the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR) and farnesoid X receptor (FXR) and several of their target genes. We hypothesised that high fat feeding would alter the gene expression of major hepatic transporters through a dysregulation of the expression of the nuclear receptors. The results demonstrated that, along with a significant increase in body fat and weight, a high-fat diet (HFD) induced a significant 2-fold increase in the expression of PXR as well as a 2-, 5- and 2·5-fold increase in the hepatic expression of the PXR target genes Abcc2, Abcb1a and Cyp3a2, respectively (P< 0·05). The expression levels of FXR were significantly increased in rats fed a HFD in addition to the increase in the expression levels of FXR target genes Abcb11 and Abcb4. The expression levels of both LXRα and LXRβ were slightly but significantly increased in rats fed a HFD, and the expression levels of their target genes Abca1 and Abcg5, but not Abcg8, were significantly increased. The expression of the nuclear receptor CAR was not significantly altered between the groups. This suggests that a HFD may induce changes in the hepatobiliary transport and metabolism of endogenous and exogenous compounds.
One-child Policy : A Macroeconomic Analysis

This paper studies the effects of a one-child policy. A benchmark without the fertility constraint is compared to a counterfactual experiment with the fertility constraint in place. The results suggest that imposing the one-child policy promotes the accumulation of human capital and increases output per capita. In partial equilibrium, an unskilled adult’s welfare is lowered by the policy. However, in general equilibrium, the policy triggers a decrease in the supply of unskilled labor, which increases the unskilled wage rate. Thus, an unskilled adult is in fact better off with the policy due to higher wages. This paper demonstrates the importance of accounting for general-equilibrium effects and heterogeneity when analyzing population policies.
Levels of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in children with Henoch-Schönlein purpura.

BACKGROUND AND PURPOSE Henoch-Schönlein purpura (HSP) is a small vessel vasculitis. Soluble adhesion molecules play a very important role in the immuno-inflammatory reaction of damaged vascular tissues. This study investigated the prognostic and diagnostic potential of soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in HSP. METHODS Serum levels of sICAM-1 and sVCAM-1 were studied in 26 children with HSP. Paired blood samples (during acute and convalescent stages) were collected from 17 of the children and assayed by enzyme-linked immunosorbent assay. Correlations with clinical manifestations were examined. Seventeen healthy children served as controls. RESULTS Both sICAM-1 and sVCAM-1 were significantly elevated at the acute stage compared with the remission stage of HSP patients versus controls (p=0.006 and p=0.0173, respectively). CONCLUSIONS Although the levels of sICAM-1 and sVCAM-1 were not correlated with the severity of clinical manifestations in HSP, these soluble adhesion molecules may serve as diagnostic markers.
Cordyceps militaris (L.: Fr.) Link – An Important Medicinal Mushroom.

Cordyceps militaris is an important medicinal mushroom useful for the extraction of several bio-metabolites for natural drugs to revitalize the various physiological systems of the body from the ancient era. The constituents of C. militaris are now using widely in the modern pharmaceutical industries. The active principles of C. militaris are beneficial to act principally as pro-sexual, anticancer, immunomodulatory, and anti-oxidant agent, let alone its others beneficial activities for most of the systems of the body. In addition, it has lots of clinical applications. The prospects of this novel mushroom could be used not only for modern medicinal manufacturers, but also for the community people for the betterment of their health. Keyword: Cordyceps militaris, Cordycepin, Immunomodulatory.
Screening for Hepatitis C in injecting drug users: a cost utility analysis.

BACKGROUND Hepatitis C is a major public health problem of increasing importance among injecting drug users, among whom screening has been proposed. We therefore estimated the cost utility of screening for hepatitis C infection among people with a history of injecting drug use in contact with drug misuse services. METHODS A spreadsheet-based model of screening using ELISA followed by polymerase chain reaction tests and treatment using combination therapy with interferon alpha and ribavirin was developed. Parameters were informed by literature review, expert opinion and a survey of current screening practice in England. A range of one-way sensitivity analyses were carried out to explore uncertainty in the results for cost effectiveness. RESULTS Screening for HCV is likely to yield benefits in the population concerned at around 28,000 pounds per quality adjusted life year. This estimate is reasonably stable when explored in extensive one-way sensitivity analysis but appeared sensitive to the proportion of HCV positive people who accept biopsy or treatment and the utility gains associated with successful drug treatment. Important other areas of uncertainty include the effects of mortality from other causes on the cost effectiveness of screening in this population and the time at which symptoms would have led to presentation in the absence of a screening programme. CONCLUSION Screening for HCV in this population is moderately cost effective, although some caution must remain in accepting this estimate given the current uncertainties in this field, and further research is required.
Electrophysiological Study of Cardiovascular Neurons in the Rostral Ventrolateral Medulla in Rats

In urethane-anesthetized rats, electrophysiological recordings of spontaneously active neurons in the vasopressor area of the rostral ventrolateral medulla were analyzed for participation in cardiovascular regulation. A total of 138 units were found which were inhibited by transient increases in mean arterial pressure elicited by intravenous injection of norepinephrine, aortic occlusion, or electrical stimulation of the hypothalamus, with 100% inhibition occurring at 148 mm Hg. Histograms of postsystolic activity showed that these units had pulse-synchronous rhythms which grew more prominent as arterial pressure increased. Furthermore, electrical stimulation of the superior laryngeal nerve, which elicited a vasodepressor response, strongly inhibited these units. Thus, these neurons were termed negatively correlated cardiovascular units. At least half of these cells project to or through the thoracic spinal cord. In addition, arterial pressure sensitivity is conveyed through carotid sinus and aortic arch afferents. Approximately half of the cardiovascular units are also excited by hypothalamic stimulation. Finally, analysis of neighboring cells showed that it is possible to distinguish between cardiovascular and respiratory units. These data are consistent with the concept of a medullary center which supports tonic sympathetic vasomotor tone and which mediates baroreceptor reflexes, as well as vascular responses of the defense reaction.
Biological denitrification of drinking water using autotrophic organisms with H2 in a fluidized‐bed biofilm reactor

Biological denitrification of drinking water was studied in a fluidized sand bed reactor using a mixed culture. Hydrogen gas was used as the reaction partner. The reaction kinetics were calculated with a double Monod saturation function. The Ks value for hydrogen was below 0.1% of saturation. No appreciable biofilm diffusion effects were detected. Reactor performance was a function of the culture's past history. Batch experiments always exhibited an accumulation of NO2−, but continuous experiments with a sufficiently long residence time always resulted in complete nitrogen removal. Rates of up to 23 mg N/L h, 25 mg N/g DW h, and 7.9 mg H2/L h were achieved. Residence times of 4.5 h would be required for complete denitrification of water containing 25 mg NO3−–N/L or approximately 1 h for every 5 mg/L.
Molecular insights into an ancient form of Paget’s disease of bone

Significance We identify an ancient and atypical form of Paget’s disease of bone (PDB) in a collection of medieval skeletons exhibiting unusually extensive pathological changes, high disease prevalence, and low age-at-death estimations. Proteomic analysis of ancient bone-preserved proteins combined with analysis of small RNAs supports a retrospective diagnosis of PDB. Remains affected by other skeletal disorders may therefore hold a chemical memory amenable to similar molecular interrogation. Abnormalities in a contemporary PDB-linked protein detected in ancient tooth samples indicate that dentition may represent an unexplored storehouse for the study of skeletal disorders. Our work provides insights into the natural history of PDB and prompts a similar revaluation of other archaeological collections. Paget’s disease of bone (PDB) is a chronic skeletal disorder that can affect one or several bones in individuals older than 55 y of age. PDB-like changes have been reported in archaeological remains as old as Roman, although accurate diagnosis and natural history of the disease is lacking. Six skeletons from a collection of 130 excavated at Norton Priory in the North West of England, which dates to medieval times, show atypical and extensive pathological changes resembling contemporary PDB affecting as many as 75% of individual skeletons. Disease prevalence in the remaining collection is high, at least 16% of adults, with age at death estimations as low as 35 y. Despite these atypical features, paleoproteomic analysis identified sequestosome 1 (SQSTM1) or p62, a protein central to the pathological milieu of PDB, as one of the few noncollagenous human sequences preserved in skeletal samples. Targeted proteomic analysis detected >60% of the ancient p62 primary sequence, with Western blotting indicating p62 abnormalities, including in dentition. Direct sequencing of ancient DNA excluded contemporary PDB-associated SQSTM1 mutations. Our observations indicate that the ancient p62 protein is likely modified within its C-terminal ubiquitin-associated domain. Ancient miRNAs were remarkably preserved in an osteosarcoma from a skeleton with extensive disease, with miR-16 expression consistent with that reported in contemporary PDB-associated bone tumors. Our work displays the use of proteomics to inform diagnosis of ancient diseases such as atypical PDB, which has unusual features presumably potentiated by yet-unidentified environmental or genetic factors.
Elucidating the Molecular Basis of Multiple Sclerosis and Understanding theDisease Pathophysiology

Multiple sclerosis (MS) is a complex, multifactorial autoimmune disorder of the central nervous system (CNS) that causes inflammation, demyelination and neurodegeneration. The increased prevalence of this disease in Arabian Gulf Countries (AGCs) has captivated the author. The following is a deliberative review of the disease with respect to its molecular basis. Briefly, it considers disease pathophysiology though the molecular composition of the cell; the genome, epigenome and mitochondrial genome; and relates these factors to environmental, etiological factors, including: vitamin D, UVR, EBV infection, smoking and obesity. All in all, this review aims to explain the reasons underlying the increasing prevalence of MS in AGCs.
A Programmable Frequency Multiplier-by-29 Architecture for Millimeter Wave Applications

This paper presents an original mmW frequency multiplier that provides the channel center frequencies of the IEEE 802.15. 3c standard from a much lower and fixed frequency of 2.16 GHz. It is composed of a voltage-controlled oscillator (VCO) whose supply is periodically switched on-and-off by the input signal, providing Periodically Repeated Oscillations Train (PROT). This multi-harmonic signal is injected into an oscillator (ILO) that locks onto the harmonic of interest, providing a continuous wave sinusoidal signal in the 60 GHz band. The CMOS 40 nm circuit consumes 32 mW and occupies only 0.07 mm 2. A theoretical approach on the synchronization of the PROT signal generator and the ILO is proposed, based on custom approximated solutions of the Van der Pol oscillator and highlighting new synchronization phenomena. Based on this theory, this novel programmable multiplication technique requires a unique fixed low frequency reference to perform multi-channel mmW LO generation. The phase noise of the output LO signal is only limited by the input low frequency reference phase noise and the frequency ratio between the output and the input signals. Thus, a 60 GHz signal has been generated with this technique with a record phase noise of -104 dBc/Hz@1 MHz offset.
Patent foramen ovale and cryptogenic stroke in older patients.

BACKGROUND Studies to date have shown an association between the presence of patent foramen ovale and cryptogenic stroke in patients younger than 55 years of age. This association has not been established in patients 55 years of age or older. METHODS We prospectively examined 503 consecutive patients who had had a stroke, and we compared the 227 patients with cryptogenic stroke and the 276 control patients with stroke of known cause. We examined the prevalences of patent foramen ovale and of patent foramen ovale with concomitant atrial septal aneurysm in all patients, using transesophageal echocardiography. We also compared data for the 131 younger patients (< 55 years of age) and those for the 372 older patients (> or = 55 years of age). RESULTS The prevalence of patent foramen ovale was significantly greater among patients with cryptogenic stroke than among those with stroke of known cause, for both younger patients (43.9% vs. 14.3%; odds ratio, 4.70; 95% confidence interval [CI], 1.89 to 11.68; P<0.001) and older patients (28.3% vs. 11.9%; odds ratio, 2.92; 95% CI, 1.70 to 5.01; P<0.001). Even stronger was the association between the presence of patent foramen ovale with concomitant atrial septal aneurysm and cryptogenic stroke, as compared with stroke of known cause, among both younger patients (13.4% vs. 2.0%; odds ratio, 7.36; 95% CI, 1.01 to 326.60; P=0.049) and older patients (15.2% vs. 4.4%; odds ratio, 3.88; 95% CI, 1.78 to 8.46; P<0.001). Multivariate analysis adjusted for age, plaque thickness, and presence or absence of coronary artery disease and hypertension showed that the presence of patent foramen ovale was independently associated with cryptogenic stroke in both the younger group (odds ratio, 3.70; 95% CI, 1.42 to 9.65; P=0.008) and the older group (odds ratio, 3.00; 95% CI, 1.73 to 5.23; P<0.001). CONCLUSIONS There is an association between the presence of patent foramen ovale and cryptogenic stroke in both older patients and younger patients. These data suggest that paradoxical embolism is a cause of stroke in both age groups.
Asymmetry at the molecular level in biology

Naturally occurring biological molecules are made of homochiral building blocks. Proteins are composed of L-amino acids (and not D-amino acids); nucleic acids such as DNA have D-ribose sugars (and not L-ribose sugars). It is not clear why nature selected a particular chirality. Selection could have occurred by chance or as a consequence of basic physical chemistry. Possible proposals, including the contribution of the parity violating the weak nuclear force, are discussed together with the mechanisms by which this very small contribution might be amplified. Homochirality of the amino acids has consequences for protein structure. Helices are right handed and beta sheets have a left-hand twist. When incorporated into the tertiary structure of a protein these chiralities limit the topologies of connections between helices and sheets. Polypeptides comprised of D-amino acids can be synthesized chemically and have been shown to adopt stable structures that are the mirror image of the naturally occurring L-amino acid polypeptides. Chirality is important in drug design. Three examples are discussed: penicillin; the CD4 antagonistic peptides; and thalidomide. The absolute hand of a biological structure can only be established by X-ray crystallographic methods using the technique of anomalous scattering.
Blue light-emitting diode built-in contact lens electrode can record human S-cone electroretinogram.

PURPOSE To develop a contact lens electrode with a built-in blue light-emitting diode (LED) to record the electroretinogram from short-wave sensitive-cone (S-cone) electroretinogram (ERG) in humans. METHODS The ERG was recorded using the blue LED (450 nm) built-in electrode under a yellow background illumination from a slide projector in five normal subjects, a patient with blue cone monochromatism, and a patient with fundus albipunctatus. For comparison, the ERG was also recorded using a yellow LED (566 nm) built-in electrode under the same background illumination in the normal subjects. RESULTS The amplitude and the peak time of the b-wave recorded with 3-Hz blue stimuli were 5.1 to 12.4 microV and 63 to 68 msec, respectively in normal subjects, 7.3 microV and 65 msec in the patient with blue cone monochromatism, and 11.4 microV and 65 msec in the patient with fundus albipunctatus. Normal subjects responded to neither 30-Hz blue stimuli nor 3-Hz yellow stimuli. CONCLUSIONS Results indicate that the b-wave recorded with 3-Hz blue stimuli is elicited from the S-cone system. This simple technique is useful for testing the human blue cone system.
Air pollution: small particles, big problems?

In this issue of EPIDEMIOLOGY two studies from opposite sides of the Atlantic Ocean underscore the global interest in the potential adverse cardiovascular effects of fine particulate matter and gaseous air pollutants. They corroborate and extend recurring findings that the small-mass air pollutants derived from combustion sources appear to exert a transient influence on autonomic function and on risk for acute cardiovascular events. The article by Holguín and coworkers from Mexico City describes the results of a longitudinal examination of nursing home residents who underwent 5-minute electrocardiographic monitoring sessions every other day for a 3-month period. The study is notable for its extensive exposure assessment and activity diaries. The investigators found that higher levels of particulate air pollution were associated with lower levels of the high-frequency component of heart rate variability (HRV). They also show data suggesting that the association between particles and HRV might be more prominent in elderly patients with hypertension. It is well known that reduced HRV in the setting of myocardial infarction is associated with greater risk of cardiac death, presumably attributable to loss of the cardioprotective effect of vagus nerve activity, which can help maintain cardiac electrical stability. However, the clinical significance of minor, transient changes in HRV, as observed in this study, is uncertain. D’Ippoliti and coworkers described the results of a case-crossover study of the effects of air pollution on acute myocardial infarction among residents of Rome between 1995 and 1997. They found that higher levels of particles and NO2 were associated with transient increases in the rate of hospitalization for acute myocardial infarction. This investigation had several important strengths, including a relatively large number of cases and a well-defined control-sampling scheme. However, the study was limited by its reliance on administrative records, incomplete information on the time of symptom onset, and absence of direct measures of particulate matter. Well-conducted studies evaluating the effects of air pollution are of great importance. It is not yet certain that air pollution has cardiovascular effects, and those effects that have been reported are typically quite small on a relative scale. Still, if these effects are true and causal, then a potentially large number of excess cases might be triggered by exposures, which affect entire populations. Development of a full understanding of the effects of particulate and gaseous pollutants on cardiovascular health will require a multidisciplinary approach with a unique and important role to be played by epidemiologists. To make rapid progress, either in identifying a causal association or in debunking an illusory one, environmental and cardiovascular epidemiologists must unite with experts in exposure assessment, cardiovascular biology, and cardiologists to design and conduct novel studies. It is also important that investigators maintain a healthy skepticism and use
Noninvasive measurements of infarct size after thrombolysis with a necrosis-avid MRI contrast agent.

BACKGROUND Gadophrin-2 is a new MRI contrast agent with high affinity for necrotic myocardium. The aim of the study was to evaluate whether noninvasive measurements of infarct size after thrombolysis are possible with gadophrin-2-enhanced MRI. METHODS AND RESULTS Coronary artery thrombosis was induced in 3 groups of dogs by the copper-coil technique. Thrombolytic therapy together with aspirin and heparin was initiated after 90 minutes of occlusion. One day (group A), 2 days (group B), or 6 days (group C) after infarction, gadophrin-2 was injected intravenously (50 micromol. kg-1). In vivo T1-weighted segmented turbo-FLASH, in vivo T2-weighted segmented half-Fourier turbo spin echo (HASTE), and T1- and T2-weighted spin-echo MRI of the excised heart were performed 24 hours after gadophrin-2 injection. Regions of strong enhancement were observed on T1-weighted images. Planimetry of short-axis MR images and of corresponding triphenyltetrazolium chloride (TTC)-stained left ventricular (LV) slices showed a close correlation between the enhanced areas and TTC-negative areas for both in vivo (r2=0.98, P<0.0001; mean difference, 0.9+/-2.0% [SD] of the LV volume [LVV]) and postmortem (r2=0.99, P<0.0001; mean difference, 0.9+/-1.4% of LVV) measurements. T2-weighted images overestimated the infarct size by 8.1+/-5.4% of LVV. The mean infarct size was 10.8+/-11.6% of LVV (group A), 22.4+/-11.7% (group B), and 5.1+/-9.3% (group C). CONCLUSIONS In this animal model, in vivo gadophrin-2-enhanced MRI could precisely determine infarct size after thrombolytic therapy. This technique may be very useful for the noninvasive evaluation of infarct size after reperfusion for AMI.