Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian and seasonal variation of endogenous ubiquinone plasma level

Coenzyme Q10 (CoQ10) or ubiquinone, a redox component of the mitochondrial electron transport chains, is a powerful antioxidant and membrane stabilizer that may prevent cellular damage during myocardial ischemia and reperfusion therapy. Coenzyme Q10 has been used primarily as an adjuvant therapy for some cardiomyopathies. However, one of the main problems in CoQ10 administration is the high variability of endogenous plasma and tissue levels, which seems to be dependent on several factors. This work explores temporal 24h and seasonal variation as well as gender and racial differences in endogenous plasma ubiquinone concentration. Coenzyme Q10 measurements (quantified by HPLC-UV) of 16 healthy volunteers were done during the daytime hours of activity beginning at 09:00h one day and ending at 09:00h the next day (13 different determinations) in two distinct months, April and October, of the year. A statistically significant circadian rhythm in plasma ubiquinone concentration that includes only the fundamental 24h component was demonstrated both in the April and October data. Furthermore, the time-point means of the ubiquinone concentration in the October study were invariably higher than those obtained in the April study. No statistically significant differences were found in CoQ10 concentration between male and female subjects, both in April and in October. In addition, racial differences were demonstrated; lower plasma ubiquinone levels were found in Caucasian compared to African subjects. However, the latter small group of subjects failed to demonstrate a circadian rhythm, neither in the April nor in the October analysis.
Diabetes Mellitus in Older Adults

The prevalence of diabetes mellitus increases with age and causes significant morbidity and poor quality of life in older adults. To review the current literature on the diagnosis and management of diabetes in the elderly, the relevant manuscripts were identified through a MEDLINE (2000–September 1, 2010) search of the English literature. The key phrase used was diabetes in older adults or diabetes in the elderly. The literature search was limited to core clinical journals that have accessible full texts. A total of 480 manuscripts were reviewed. Managing diabetes in older adults is a challenging task. Some features of the disease are unique to the older patient. Several new antidiabetic agents are now available for clinical use, and yet very few clinical trials have been carried out in this age group. For many older adults, maintaining independence is more important than adherence to published guidelines to prevent diabetes complications. The goals of diabetes care in older adults are to enhance quality of life without subjecting the residents to inappropriate interventions.
STAT2 Is a Primary Target for Measles Virus V Protein-Mediated Alpha/Beta Interferon Signaling Inhibition

ABSTRACT Measles virus, a member of the Morbillivirus family, infects millions of people each year despite the availability of effective vaccines. The V protein of measles virus is an important virulence factor that can interfere with host innate immunity by inactivating alpha/beta interferon (IFN-α/β) and IFN-γ signaling through protein interactions with signal transducer and activator of transcription proteins STAT1 and STAT2. Here we demonstrate that although STAT1 interference results from protein interactions within a V protein N-terminal region encompassed by amino acids 110 to 130, detection of STAT1 interaction and IFN-γ signaling inhibition requires the presence of cellular STAT2. Cell-specific variability in STAT1 interference was observed to correlate with V protein expression level. A more direct target for measles virus V protein-mediated IFN-α/β evasion is STAT2. Results indicate that the widely conserved C-terminal zinc finger domain of measles virus V protein is both necessary and sufficient to bind STAT2 and disrupt IFN-α/β signal transduction. Mutagenesis and molecular modeling define a contact surface for STAT2 association that includes aspartic acid residue 248 as critical for STAT2 interference and IFN antiviral immune suppression. These findings clearly define the molecular determinants for measles virus IFN evasion and validate specific targets as candidates for therapeutic intervention.
Effects of linear and daily undulating periodized resistance training programs on measures of muscle hypertrophy: a systematic review and meta-analysis

Background Periodization is an important component of resistance training programs. It is meant to improve adherence to the training regimen, allow for constant progression, help in avoiding plateaus, and reduce occurrence and severity of injuries. Previous findings regarding the effects of different periodization models on measures of muscle hypertrophy are equivocal. To provide a more in-depth look at the topic, we undertook a systematic review of the literature and a meta-analysis of intervention trials comparing the effects of linear periodization (LP) and daily undulating periodization (DUP) resistance training programs on muscle hypertrophy. Materials and Methods A comprehensive literature search was conducted through PubMed/MEDLINE, Scopus, Web of Science, SPORTDiscus, Networked Digital Library of Theses and Dissertations (NDLTD) and Open Access Theses and Dissertations (OATD). Results The pooled standardized mean difference (Cohen’s d) from 13 eligible studies for the difference between the periodization models on muscle hypertrophy was −0.02 (95% confidence interval [−0.25, 0.21], p = 0.848). Conclusions The meta-analysis comparing LP and DUP indicated that the effects of the two periodization models on muscle hypertrophy are likely to be similar. However, more research is needed in this area, particularly among trained individuals and clinical populations. Future studies may benefit from using instruments that are more sensitive for detecting changes in muscle mass, such as ultrasound or magnetic resonance imaging.
Unexpectedly high prevalence of akathisia in cancer patients

ABSTRACT Objectives: Complications of neuropsychiatric disorders are often detected in cancer patients. Adjustment disorders, depression, or delirium are common psychiatric disorders in these patients, and drug-induced neuropsychiatric problems are sometimes referred for psychiatric consultation. Prochlorperazine and other antiemetic drugs that are phenothiazine derivates are also reported to cause akathisia due to the blockade of the dopamine receptor in the central nervous system, but the prevalence of akathisia in patients undergoing cancer treatment has not been reported. This study seeks to explore the prevalence of such drug-induced syndromes (e.g., akathisia) in this population. Methods: This present study was a prospective study. The subjects of this study were 483 consecutive patients with cancer who had been referred to the Department of Psychiatry in Kanagawa Prefecture Cancer Center from February 1, 2004, to November 30, 2005. Trained psychiatrists conducted a nonstructured psychiatric interview and neurologic examination to establish psychiatric diagnoses according to DSM-IV and the presence or absence of drug-induced extra pyramidal symptoms. The past and current medications used in their cancer treatment were also examined in detail for an accurate evaluation. Results: A psychiatric diagnosis was made in 420 (87.0%) of the 483 cancer patients examined, and akathisia, a drug-induced movement disorder, was unexpectedly prevalent among the patients; 20 of 420 (4.8%) patients had developed akathisia from an antiemetic drug, prochlorperazine. Significance of results: Diagnosing such adverse drug reactions may be difficult due to complicating factors in cancer treatment, and the inner restlessness observed in akathisia is likely to be regarded as a symptom of a primary psychiatric disorder. The authors suggest that oncologists should optimize the use of antiemetic drugs and be aware of akathisia as a possible complication of cancer treatment.
Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

Abstract Objective: To examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life. Design: Cohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure. Setting: Maternity services in the Grampian region of Scotland. Participants: Women selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970. Main outcome measures: Current vital and cardiovascular health status ascertained through postal questionnaire survey, clinical examination, linkage to hospital discharge, and mortality data. Results: There were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4). Conclusions: Hypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases. What is already known on this topic Much is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to women Retrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later life What this study adds Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertension Women who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart disease Long term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)
Bilirubin is an independent factor inversely associated with glycated hemoglobin level in pediatric patients with type 1 diabetes

Bilirubin is a potent antioxidant, and serum total bilirubin (STB) concentrations correlate negatively with cardiovascular risk. In adult diabetic patients and in healthy adults, a negative correlation between STB and glycated hemoglobin (HbA1c) has been reported. We investigated whether there is such an association in children and adolescents with type 1 diabetes mellitus.
Shear stress-induced dilation is attenuated in skeletal muscle arterioles of hypertensive rats.

Hypertension is thought to alter many of the functions of the vascular endothelium. The present study examines whether shear stress-induced endothelium-dependent skeletal muscle arteriolar dilation is compromised in genetically hypertensive rats. Changes in the diameter of isolated, perfused arterioles (approximately 60 microns) from gracilis muscles of 12-week-old normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR) were investigated. At a constant perfusion pressure (80 mm Hg), the active diameter of NWR and SHR arterioles was 57.1 +/- 2.0 and 50.9 +/- 3.5 microns, respectively (mean +/- SEM), while the passive diameter (in Ca(2+)-free solution) was 113.2 +/- 3.1 and 100.6 +/- 2.9 microns, respectively. Increases in wall shear stress (from 0 to 100 dyne/cm2) elicited by increases in perfusate flow (from 0 to 25 microL/min) resulted in marked increases in the diameter of NWR arterioles, but such increases produced substantially smaller dilations in SHR arterioles (43.0 versus 18.9 microns). The prostaglandin synthesis inhibitor indomethacin (10(-5) mol/L) significantly attenuated the shear stress-induced dilations in both strains of rats. In contrast, the nitric oxide synthase inhibitor N omega-nitro-L-arginine (10(-4) mol/L) significantly shifted the shear stress-diameter curve to the right in vessels from NWR (by 50 dyne/cm2) but not in those from SHR. Thus, in gracilis muscle arterioles of SHR, the reduced dilation to increases in shear stress seems to be due to the lack of nitric oxide synthesis and/or release in response to shear stress. (ABSTRACT TRUNCATED AT 250 WORDS)
Side effects of antipsychotic drugs

PREVIEW Clearly, the use of antipsychotic drugs can be extremely helpful in elderly patients to reduce psychotic symptoms and agitation. However, these drugs may produce serious side effects, such as parkinsonism, akathisia, dystonia, and tardive dyskinesia, that can range in intensity from mild to severe. In this article, the authors describe how to use antipsychotic agents in the most careful fashion possible.
Radiation risks potentially associated with low-dose CT screening of adult smokers for lung cancer.

PURPOSE To estimate the radiation-related lung cancer risks associated with annual low-dose computed tomographic (CT) lung screening in adult smokers and former smokers, and to establish a baseline risk that the potential benefits of such screening should exceed. MATERIALS AND METHODS The estimated lung radiation dose from low-dose CT lung examinations corresponds to a dose range for which there is direct evidence of increased cancer risk in atomic bomb survivors. Estimated dose-, sex-, and smoking status-dependent excess relative risks of lung cancer were derived from cancer incidence data for atomic bomb survivors and used to calculate the excess lung cancer risks associated with a single CT lung examination at a given age in a U.S. population. From these, the overall radiation risks associated with annual CT lung screening were estimated. RESULTS A 50-year-old female smoker who undergoes annual CT lung screening until age 75 would incur an estimated radiation-related lung cancer risk of 0.85%, in addition to her otherwise expected lung cancer risk of approximately 17%. The radiation-associated cancer risk to other organs would be far lower. If 50% of all current and former smokers in the U.S. population aged 50-75 years received annual CT screening, the estimated number of lung cancers associated with radiation from screening would be approximately 36,000, a 1.8% (95% credibility interval: 0.5%, 5.5%) increase over the otherwise expected number. CONCLUSION Given the estimated upper limit of a 5.5% increase in lung cancer risk attributable to annual CT-related radiation exposure, a mortality benefit of considerably more than 5% may be necessary to outweigh the potential radiation risks.
Phenotyping nematode feeding sites: three-dimensional reconstruction and volumetric measurements of giant cells induced by root-knot nematodes in Arabidopsis.

The control of plant parasitic nematodes is an increasing problem. A key process during the infection is the induction of specialized nourishing cells, called giant cells (GCs), in roots. Understanding the function of genes required for GC development is crucial to identify targets for new control strategies. We propose a standardized method for GC phenotyping in different plant genotypes, like those with modified genes essential for GC development. The method combines images obtained by bright-field microscopy from the complete serial sectioning of galls with TrakEM2, specialized three-dimensional (3D) reconstruction software for biological structures. The volumes and shapes from 162 3D models of individual GCs induced by Meloidogyne javanica in Arabidopsis were analyzed for the first time along their life cycle. A high correlation between the combined volume of all GCs within a gall and the total area occupied by all the GCs in the section/s where they show maximum expansion, and a proof of concept from two Arabidopsis transgenic lines (J0121 ≫ DTA and J0121 ≫ GFP) demonstrate the reliability of the method. We phenotyped GCs and developed a reliable simplified method based on a two-dimensional (2D) parameter for comparison of GCs from different Arabidopsis genotypes, which is also applicable to galls from different plant species and in different growing conditions, as thickness/transparency is not a restriction.
T lymphocytes and silica-induced pulmonary inflammation and fibrosis in mice.

BACKGROUND: Silica-induced pulmonary inflammation and fibrosis in animals provides a good model for chronic pulmonary inflammation and fibrosis. Although lymphocytes are implicated in the pathogenesis of pulmonary fibrosis, experimental models using silica-treated athymic nude mice have not been successful in showing the fibrogenic mechanism regulated by T cells. The aim of this study was to re-evaluate the role of T lymphocytes in the development of silicosis by comparing the response to silica administration of nude athymic mutants with that of euthymic animals. METHODS: Suspensions of silica particles were transnasally administered to nude athymic mice (Balb/c nu/nu) as well as to their euthymic littermates (Balb/c nu/+). The degree of pulmonary inflammation and fibrosis was assessed on days 14, 28, and 56 based upon histological observation, analysis of collagen deposition in the lungs, and analysis of the cellular constituent, protein, and phospholipid content in the bronchoalveolar lavage fluid. RESULTS: Histologically, athymic mice developed less severe interstitial pneumonitis than euthymic mice. In euthymic mice the lung hydroxyproline content increased with time after silica administration from 6.48 (0.38) micrograms hydroxyproline/mg dry lung weight on day 0 to 8.87 (0.41) micrograms/mg on day 56. A gradual increase in lung hydroxyproline content was also observed in athymic mice but the increase was significantly smaller than in euthymic mice (6.63 (0.43) micrograms/mg on day 0, 7.90 (0.19) micrograms/mg on day 56). Administration of silica resulted in an increase in the number of macrophages and neutrophils and in the total protein and phospholipid content of the bronchoalveolar lavage (BAL) fluid in both mouse strains. No significant difference was detected between athymic and euthymic mice in the numbers of macrophages, but the increase in neutrophils in the BAL fluid of athymic mice was significantly smaller than in euthymic mice on days 14 and 56. The total protein and phospholipid content of the BAL fluid from athymic mice was lower than that from euthymic mice. CONCLUSIONS: T lymphocytes appear to be involved in the pathogenesis of silica-induced pneumonitis. Since pulmonary fibrosis develops even in nude athymic mice, T cells do not seem to play a primary part in fibrogenic response but they regulate, at least to some extent, the response of inflammatory cells and fibrogenesis of the lung.
Prevalence of Dry Eye Disease in Mongolians at High Altitude in China: The Henan Eye Study

Purpose: To estimate the prevalence of dry eye disease, analyze the associations between dry eye symptoms and signs, and identify the risk factors in an elderly Mongolian population at high altitude in China. Methods: A population-based survey was conducted in 2006. A total of 2,486 Mongolians age 40 and older were selected. Symptoms of dry eye were assessed using a 6-item validated questionnaire. Dry eye disease was defined if participants reported one or more symptoms often or all the time. Positive signs included a tear-film breakup time of ≤10 seconds, a Schirmer test score of ≤ 5mm, or a fluorescein staining score ≥ 1 in one or both eyes. Presence of dry eye symptoms and positive signs were analyzed. Correlations between symptoms and signs, and risk factors were evaluated in a multivariate model. Results: Of the 1,816 participants, 50.1% (95% confidence interval, 47.8–52.4) were symptomatic. Tear-film breakup time of ≤ 10 seconds was 37.7% (95% confidence interval, 35.5–39.9). A Schirmer test score of ≤ 5mm was 19.9% (95% confidence interval, 18.4–22.1). Fluorescein staining score ≥ 1 was 6.0% (95% confidence interval, 4.9–7.1). The correlation between dry eye symptoms and positive signs (tear-film breakup time of ≤ 10 seconds[r = 0.414, P < 0.001], Schirmer test score of ≤ 5mm [r = 0.164, P = 0.001], and fluorescein staining score ≥1 [r = 0.361, P < 0.001]) were statistically significant. Independent risk factors included increased age, age-related cataract and pterygium. Conclusion: This study demonstrates a high prevalence rate of dry eye disease in a Mongolian population. Dry eye signs were significantly associated with dry eye symptoms.
A glucocorticoid receptor gene haplotype (TthIII1/ER22/23EK/9beta) is associated with a more aggressive disease course in multiple sclerosis.

CONTEXT In patients with multiple sclerosis (MS), glucocorticoids (GCs) might not be sufficiently able to restrain the immune system, possibly due to decreased GC sensitivity. This may be, at least partially, genetically determined. Previously, we reported a more aggressive disease course in patients with the glucocorticoid receptor (GR) gene ER22/23EK polymorphism, which has been shown to decrease GC sensitivity. OBJECTIVE In 646 MS patients and 317 healthy controls, we investigated whether haplotypes, including the ER22/23EK polymorphism or the GR 9beta polymorphism, which is also associated with a relative GC resistance, were associated with a more aggressive disease course. PATIENTS AND METHODS Polymorphisms in the GR gene (9beta, ER22/23EK, TthIIII, BclI, and N363S), which have previously been associated with altered GC sensitivity were determined and haplostructure was characterized. We evaluated whether the haplotypes were associated with disease susceptibility and several other disease characteristics. The association with disease progression was analyzed using Cox regression with time to Expanded Disability Status Score 6 as outcome. RESULTS None of the haplotypes was associated with disease susceptibility, age at onset, or onset type. Haplotype 6 (TthIIII, ER2223EK, and 9beta-G) was associated with a more rapid disease progression (hazard ratio 2.3; 95% confidence interval 1.5-3.7; P < 0.001). This seems to result from the presence of ER22/23EK, and not from the 9beta and TthIIII polymorphisms. CONCLUSIONS MS patients carrying the haplotype 6 (TthIIII, ER22/23EK, and 9beta) have a more aggressive disease course. This is probably due to the presence of the polymorphism ER22/23EK, which causes a decreased GC sensitivity.