Miracle-dz/UniFAR-FTUs huggingface dataset:
Social isolation increases number of newly proliferated cells in hippocampus in female flinders sensitive line rats

Genetic background influences the responsiveness to stress and plays a crucial role in the pathophysiology of depression. In an animal model of depression, Flinders Sensitive Line rats, and Sprague Dawley controls we analyzed if 7 weeks of social isolation of adult animals affect the number of newly proliferated cells in the dentate gyrus or mRNAs of Neuropeptide Y (NPY), the NPY‐Y1 receptor, nociceptin, BDNF, and the serotonin 5HT1A and 5HT2A receptors, which are molecules involved in hippocampal plasticity. Since depressive illness more frequently affects women than men, and females seem to respond differently to stressful experiences than males, female rats were used in this study. Bromodeoxyuridine, which is a thymidin analogue that is incorporated into the DNA of newly formed cells, was administered during 9 days to even out the effects of hormonal fluctuations. Social isolation increased the number of newly proliferated Bromodeoxyuridine‐immunoreactive cells in the Flinders Sensitive Line rats, whereas it had no impact on the number of cells in the Sprague Dawley strain. Group housed Sprague Dawley rats had a higher expression of BDNF, NPY, and the serotonin 5HT2A receptor mRNA than “depressed” Flinders Sensitive Line. Social isolation downregulated these molecules in Sprague Dawley but not in Flinders Sensitive Line rats thereby eliminating the differences between the two strains. We demonstrate strain and gender specific responses to stress induced regulation of factors important for hippocampal plasticity. © 2007 Wiley‐Liss, Inc.
Rate of testicular maturation, in relation to gonadotrophin and testosterone levels, in quail exposed to various artificial photoperiods and to natural daylengths.

Rates of testicular growth and plasma levels of FSH, LH and testosterone were determined in Japanese quail exposed to various fixed photoperiods (number of hours of light: number of hours of darkness): 12L : 12D, 13L : 11D, 14L : 10D, 16L : 8D and 20L : 4D and to natural daylengths. All five artificial photoperiods stimulated spermatogenesis, with the testes reaching maturity after 30-40 days. Maximum rates of testicular growth occurred with 14L : 10D, 16L : 8D or 20L : 4D but the rate was reduced by 50% in birds exposed to 12L : 12D. This reduction was due to decreased growth in the seminiferous tubule epithelium (and hence in tubule diameter); the duration of spermatogenesis hardly being affected. Near maximum growth rates occurred with 13L : 11D. The hormone profiles offer an explanation for the differential rates of testicular growth. In the three longest photoperiods, FSH rose from 20 ng/ml to peak levels of 300-400 ng/ml after 10 days. As the testes matured, so the level of FSH decreased to 50-100 ng/ml. This pattern was not seen under 12L : 12D ; the level of FSH rose slowly to about 100 ng/ml and showed no peak of secretion. With 13L : 11D a small peak was found, which decreased at maturity. In quail with testes is greater than 1500 mg, the level of FSH was invariably about 100 ng/ml. Patterns of LH secretion were rather similar with all treatments, but testosterone was affected by photoperiod; lower levels were found under 12L : 12D than 20L : 4D. The rate of photoperiodically induced testicular growth was proportional to the levels of FSH, and possibly also testosterone, in the circulation. Outdoors, testicular growth began when daylengths reached about 12 h. Maturity occurred within the next 40 days. The levels of FSH rose steadily but did not show a peak of secretion. In general, the highest levels of hormone were found in July just before gonadal regression which occurred when the daylengths were still quite long.
Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) Trial.

BACKGROUND Patients with chronic kidney disease are at increased risk for cardiovascular (CV) events. METHODS We randomly assigned 1,094 African Americans with hypertensive nephrosclerosis (glomerular filtration rate [GFR], 20 to 65 mL/min/1.73 m(2) [0.33 to 1.08 mL/s]) to initial antihypertensive treatment with either: (1) a beta-blocker, metoprolol; (2) an angiotensin-converting enzyme inhibitor, ramipril; or (3) a dihydropyridine calcium channel blocker, amlodipine, and either a usual-blood pressure (BP) or low-BP treatment goal. Using a design powered to detect renal outcome differences, we compared the effect of treatment on the CV event rate (cardiac death, myocardial infarction, stroke, and heart failure) during a mean follow-up period of 4.1 years and determined baseline factors that predict CV outcomes. RESULTS Thirty-one patients died of CV disease (0.7%/patient-year), and 149 patients experienced at least 1 CV outcome (3.3%/patient-year). Overall, 202 CV events (4.5%/patient-year) occurred. The CV outcome rate was not related significantly to randomized interventions. In multivariable analyses, 7 baseline risk factors remained independently associated with increased risk for the CV composite outcome after controlling for age, sex, baseline GFR, and baseline proteinuria group: pulse pressure, duration of hypertension, abnormal electrocardiogram result, non-high-density lipoprotein cholesterol level, serum urea nitrogen level, urine protein-creatinine ratio, urine sodium-potassium ratio, and annual income less than 15,000 dollars. CONCLUSION Neither randomized class of antihypertensive therapy nor BP level had a significant effect on the occurrence of CV events, possibly because of limited power. However, this analysis identifies unique and potentially modifiable CV risk factors in this high-risk cohort.
Treating diabetes today with gliclazide MR: a matter of numbers

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by worsening hyperglycaemia. Lowering haemoglobin A1c to below or around 7% has been shown to reduce microvascular and neuropathic complications of diabetes. The ongoing uncertainty regarding whether intensive glycaemic control can reduce the increased risk of cardiovascular disease (CVD) in people with T2DM stirred the launch of the recent long‐term megatrials. These trials compared the effects of intensive vs. standard control on vascular complications in relatively high CV risk participants with T2DM. While in Veterans Affairs Diabetes Trial, and Action to Control Cardiovascular Risk in Diabetes, the effect of glucose optimization resulted either in no protection or in an excessive CVD death, the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial showed that intensive glycaemic control reduced the risk of combined major macrovascular and microvascular events. In this trial, the glucose control strategy was based on gliclazide MR at randomization in all patients and then further sequential addition of other glucose‐lowering drugs. Several studies showed that gliclazide has antioxidant properties, reduces markers of endothelial inflammation, and prevents glucose‐induced apoptosis of endothelial cells. These positive antioxidant effects are not confined to the vascular wall but they are effective also in the β cells. These properties are important because (i) in patients with atherosclerotic process, microvascular abnormalities may hasten disease progression and (ii) slowing the microvascular complications may have a potentially remarkable effect on the natural history of macrovascular disease.
Exposure assessment of oxidant gases and acidic aerosols.

Clearly the presence of high ozone and acidic species in North America is primarily dependent upon photochemical air pollution. Evidence shows, however, that high acid exposures may occur in specific types of areas of high sulfur fuel use during the winter. At the present time, our concerns about exposure to local populations and regional populations should be directed primarily toward the outdoor activity patterns of individuals in the summer, and how those activity patterns relate to the location, duration, and concentrations of ozone and acid aerosol in photochemical air pollution episodes. Lioy & Dyba (23) and Mage et al (33) have examined the activity patterns of children in summer camps. Because they spend more time outside than the normal population, these children form an important group of exercising individuals subject to photochemical pollution exposures. The dose of ozone inhaled by the children in the two camps was within 50% (23) and 25% (33) of the dose inhaled by adults in controlled clinical situations that produced clinically significant decrements in pulmonary function and increased the symptoms after 6.6 hr exposure in a given day (12, 30). The chamber studies have used only ozone, whereas in the environment this effect may be enhanced by the presence of a complex mixture. The work of Lioy et al (27) in Mendham, New Jersey found that hydrogen ion seemed to play a role in the inability of the children to return immediately to their normal peak expiratory flow rate after exposure. The camp health study conducted in Dunsville, Ontario suggested that children participating in a summer camp where moderate levels of ozone (100 ppb) but high levels of acid (46 micrograms/m3) occurred during an episode had a similar response. Thus, for children or exercising adults who are outdoors for at least one hour or more during a given day, the presence and persistence of oxidants in the environment are of particular concern. Lippmann (19, 30) has suggested that the complex mixture of pollutants in the atmosphere increased the decrements in pulmonary function of children in camps, since their decrements were similar to those observed at higher ozone concentrations in the clinical studies (30). This phenomenon must be investigated in future research studies since there appears to be a potential for enhanced exposure and effects. Ozone is present for many hours during the day in summer during episodes of photochemical air pollution. (ABSTRACT TRUNCATED AT 400 WORDS)
Lipid-lowering drug therapies: the evidence

Abbreviations: CARE, Cholesterol and Recurrent Events; LIPID, Long-term Intervention with Pravastatin in Ischaemic Disease. Corresponding author: Professor Chris Packard, fax +44 (0)141 211 4322, email chrispackard@compuserve.com CAB InternationalPNSProceedings of the Nutrition Society (2000)0029-6651© Nutrition Society 2000 593 59423Ca diovascular diseas risk: lifestyle v. dr gsC. Packard4 3 42 2© Nutrition Society 2000
Prospective Study of Quality of Life of Patients Receiving Treatment for Prostate Cancer

Background: No research was found that compared quality of life (QOL) outcomes of prostate cancer patients receiving intensity-modulated radiation therapies with prostate cancer patients receiving radical prostatectomy. Objectives: To (a) describe differences in QOL before and after three types of treatment for prostate cancer: radical prostatectomy, intensity-modulated radiation therapy + seed implantation (permanent brachytherapy), or intensity-modulated radiation therapy + high dose rate radiotherapy (temporary brachytherapy); and (b) investigate demographic, physical, and psychosocial variables that impact QOL of men with prostate cancer. Methods: Data were collected on three occasions: baseline (prior to treatment), 1 month, and 3 months after beginning treatment. Measures included biographic data, physiological, and psychological measures. Analysis of variance and hierarchical regression were used to examine patterns, describe differences, and identify predictors of QOL in the three treatment groups. QOL was conceptualized as a multidimensional construct that included physical, psychological, social, and functional well-being and prostate cancer concerns. Results: Groups differed significantly in bowel and urinary symptom scores and prostate cancer concerns at baseline, and in urinary and depressive symptoms at 3 months. There were no significant group differences at 1 month. Discussion: Significant differences were found in QOL as measured with the Functional Assessment of Cancer Treatment-Prostate after treatment with radical prostatectomy, intensity-modulated radiation therapy + seed implantation, or intensity-modulated radiation therapy + high dose rate radiotherapy. Findings may provide healthcare providers with knowledge about treatment sequelae for prostate cancer, enable healthcare providers to educate patients about QOL outcomes of treatment for prostate cancer, and enable patients to make more informed treatment decisions.
Fuzzy Support Vector Classification Based on Fuzzy Chance Constrained Programming

This paper is concerned with the fuzzy support vector classification in which the type of both the output of the training point and the value of the final fuzzy classification function is triangle fuzzy number. First, the fuzzy classification problem is formulated as a fuzzy chance constrained programming. Then we transform this programming into its equivalence quadratic programming. As a result, we propose fuzzy support vector classification algorithm. In order to show its rationality of the algorithm, an example is presented
Structure of the Web Searcher's Query Modifications: Sequential, Branching, Merging, Re-Merging and

This A non-linear model of query modifications during a single session of user searching on the Web is evaluated. In addition to a sequential query modification, in which any query may be reformulation of its direct predecessor, the model allows non-linear interpretation of query reformulations: branching, merging, re-merging (merging of earlier branched chains) and non-sequential execution of logically linear chains of queries. To detect short-term (i.e. during a single time session of interaction with the Web search engine) dependencies between user’s queries we use different query-to-query similarity metrics and consider query-on-query(ies) dependency as similarity of current query to queries submitted earlier in a time session. Usage of different metrics leads to different but complimentary results. The method is applied to query logs of the Yandex, the major Russian search engine. Regardless of difference of results of different metrics, the findings are coincide: about 20% of time sessions containing 3 and more distinct queries contain such combinations of queries which can be interpreted as non-linearities: branchings are occurred in 12% of sessions; mergings are occurred in 6%, and re-mergings in 3%. Number of branches are a little bigger than two; the first branch is smaller then the last. A merging search is frequently executed in the re-merging manner. The last merging chain is smaller then the first one. Keywords— query modification, branching, merging, re-merging
Electron Microscopic Study of a Slime Layer

Slime layers are being studied in our laboratories in an attempt to understand their functions in the control of pollution in natural streams. A method for fixing, staining, and embedding microorganisms in the intact slime has been developed. In this method, epoxy resin discs are placed in a holder and are introduced into a simulated stream. After various periods of time the discs are punched out of the holder into the fixative. The disc with the attached slime is fixed, stained (4% osmium tetroxide plus ruthenium red), dehydrated, and embedded in epoxy resin so that thin sections can be cut through the vertical plane of the slime mass. Such thin sections permit detailed examination of the attached layer, the surface-slime interface, the spatial relationships between cells in the vertical slime structure, and the strands of extracellular material between and around cells. No special attachment structures were noted as the cells appeared to be attached to the surface by extracellular material alone. This material was observed in strands and netlike forms between cells which are positioned 1 to 4 μm apart in the slime.
Loss of phosphatase and tensin homolog (PTEN) in myeloid cells controls inflammatory bone destruction by regulating the osteoclastogenic potential of myeloid cells

Objective Local bone destruction in rheumatic diseases, which often leads to disability and severely reduced quality of life, is almost exclusively mediated by osteoclasts. Therefore, it is important to understand pathways regulating the generation of osteoclasts. Here, we analysed the impact of the Phosphoinositide-3-Kinase (PI3K)/Phosphatase and tensin homolog (PTEN) axis on osteoclast generation and bone biology under basal and inflammatory conditions. Methods We analysed osteoclastogenesis of wildtype (wt) and PTEN−/− cells in vitro and in vivo, pit resorption and qPCR of osteoclasts in vitro. Mice with a myeloid cell-specific deletion of PTEN and wt littermate mice were investigated by bone histomorphometry and clinical and histological assessment in the human tumour necrosis factor (TNF)-transgenic (hTNFtg) arthritis model. Results We show that myeloid-specific PTEN−/− mice display increased osteoclastogenesis in vitro and in vivo compared to wt mice. Loss of PTEN did not affect the generation or survival of osteoclast precursor cells. However, PTEN deficiency greatly enhanced receptor activator of nuclear factor κ-B ligand (RANKL)-induced expression of the master transcription factor of osteoclastogenesis, nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), resulting in markedly increased terminal differentiation of osteoclasts in vitro. We also observed increased osteoclastogenesis under inflammatory conditions in the hTNFtg mouse model of arthritis, where hTNFtg/myeloid-specific PTEN−/− mice displayed enhanced local bone destruction as well as osteoclast formation in the inflamed joints. The extent of synovial inflammation, however, as well as recruitment of osteoclast precursor cells was not different between wt and myeloid-specific PTEN−/− mice. Conclusions These data demonstrate that loss of PTEN and, therefore, sustained PI3-Kinase signalling in myeloid cells especially, elevates the osteoclastogenic potential of myeloid cells, leading to enhanced inflammatory local bone destruction. Therefore, although our study allows no direct translational conclusion since we used a conditional knockout approach, the therapeutic targeting of the PI3-Kinase pathway may be of benefit in preventing structural joint damage.
Ferroportin (Q248H) mutations in African families with dietary iron overload

Background: Dietary iron overload found in sub‐Saharan Africa might be caused by an interaction between dietary iron and an iron‐loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C‐reactive protein (CRP) were examined in 19 southern African families.
A test of the metabolic cost of cushioning hypothesis during unshod and shod running.

PURPOSE This study aimed to investigate the effects of surface and shoe cushioning on the metabolic cost of running. In running, the leg muscles generate force to cushion the impact with the ground. External cushioning (surfaces or shoes) may reduce the muscular effort needed for cushioning and thus reduce metabolic cost. Our primary hypothesis was that the metabolic cost of unshod running would decrease with a more cushioned running surface. We also hypothesized that because of the counteracting effects of shoe cushioning and mass, unshod running on a hard surface would have approximately the same metabolic cost as running in lightweight, cushioned shoes. METHODS To test these hypotheses, we attached 10- and 20-mm-thick slats of the same foam cushioning used in running shoe midsoles to the belt of a treadmill that had a rigid deck. Twelve subjects who preferred a midfoot strike pattern and had substantial barefoot/minimalist running experience ran without shoes on the normal treadmill belt and on each thickness of foam. They also ran with lightweight, cushioned shoes on the normal belt. We collected V˙O2 and V˙CO2 to calculate the metabolic power demand and used a repeated-measures ANOVA to compare between conditions. RESULTS Compared to running unshod on the normal belt, running unshod on the 10-mm-thick foam required 1.63% ± 0.67% (mean ± SD) less metabolic power (P = 0.034) but running on the 20-mm-thick foam had no significant metabolic effect. Running with and without shoes on the normal belt had similar metabolic power demands, likely because the beneficial energetic effects of cushioning counterbalanced the detrimental effects of shoe mass. CONCLUSIONS On average, surface and shoe cushioning reduce the metabolic power required for submaximal running.
Echocardiography, a non-invasive method for the assessment of cardiac function and morphology in preclinical drug toxicology and safety pharmacology

Background: Echocardiography (EC) is a method used for the investigation of cardiac morphology and function. Two-dimensional EC gives a visualisation of the morphology of the heart. M-mode EC allows heart function to be monitored. Pulsed Doppler EC is the method of choice to measure blood flows. Objective: To describe the information EC can provide for cardiovascular investigation in laboratory animals, with a special focus on the potential helpfulness of EC in preclinical toxicology and safety pharmacology. Methods: This review includes publications describing the methodology of EC and its application to several animal species used in biological experimentation. Results/conclusion: EC has been established in dogs, monkeys, rodents, rabbits and pigs. As demonstrated by experiments in different species, EC can be particularly helpful in toxicology and safety pharmacology, based on the amount of information it can give on the causes and consequences of drug adverse effects on the cardiovascular system. Furthermore, EC does not require any surgery and is therefore a key refinement compared to invasive methods generally used for investigating the cardiovascular function in laboratory animals. Despite some limitations of the method (the need for trained people, time required for an accurate EC recording, lack of current validation), EC should be further developed in preclinical toxicology and safety pharmacology.