Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Neonatal Exposure to Diethylstilbestrol, Coumestrol, and β-Sitosterol on Pituitary Responsiveness and Sexually Dimorphic Nucleus Volume in the Castrated Adult Rat

Abstract The neonatal hormone enviroment influences the sexually differentiated patterns of development. Estrogens, derived from intracerebral aromatization, promote male pattern development of the central nervous system. The purpose of this study was to determine the effects of neonatal exposure to environmental estrogens on luteinizing hormone (LH) secretion and development of the sexually dimorphic nucleus of the medial preoptic area (SDN-POA) in castrated adult rats. Neonatal rats of both sexes received injections of either corn oil, 0.1 μg diethylstilbestrol (DES), 3 μg β-sitosterol (B1), 30 μg β-sitosterol (B2), 0.1 μg coumestrol (C1), 1 μg coumestrol (C2), or 10 μg coumestrol (C3) on Day 1-10 of life and were castrated on Day 21. Right heart catheters were placed on Day 42, and GnRH (50 ng/kg) was administered. Blood was sampled for LH at 0-, 5-, 10-, 15-, and 30-min intervals. All doses of β-sitosterol and coumestrol elicited increased basal levels of LH in females. In males, B1, B2, C2, and C3 increased basal levels of LH. The GnRH-induced LH increase was prevented in females treated with diethylstilbestrol and 10 μg of coumestrol. Males in all treatment groups exhibited GnRH-induced LH surges. The animals were sacrificed by decapitation on Day 49. Volumes of the SDN-POA of the groups were compared. Treatment with the agents did not result in significantly increased SDN volume in females; nor was there a difference in SDN size among the male groups. These data show that exposure to environmental estrogens early in development alters both postpuberal pituitary response to GnRH and basal LH secretion in females and alters only basal LH secretion in males. No significant enlargement (i.e., masculinization) of the SDN-POA was exhibited.
Variability and progression in competitive performance of Paralympic swimmers

Abstract Analysis of variability and progression in performance of top athletes between competitions provides information about performance targets that is useful for athletes, practitioners, and researchers. In this study, 724 official finals times were analysed for 120 male and 122 female Paralympic swimmers in the 100-m freestyle event at 15 national and international competitions between 2004 and 2006. Separate analyses were performed for males and females in each of four Paralympic subgroups: S2–S4, S5–S7, S8–S10 (most through least physically impaired), and S11–S13 (most through least visually impaired). Mixed modelling of log-transformed times, with adjustment for mean competition times, was used to estimate variability and progression. Within-swimmer race-to-race variability, expressed as a coefficient of variation, ranged from 1.2% (male S5–S7) to 3.7% (male S2–S4). Swimming performance progressed by approximately 0.5% per year for males and females. Typical variation in mean performance time between competitions was ∼1% after adjustment for the ability of the athletes in each competition, and the Paralympic Games was the fastest competition. Thus, taking into account variability, progression, and level of competition, Paralympic swimmers who want to increase substantially their medal prospects should aim for an annual improvement of at least 1–2%.
Optic nerve head perfusion in normal eyes and eyes with glaucoma using optical coherence tomography-based microangiography.

BACKGROUND To investigate the differences of perfusion in the optic nerve head (ONH) between normal and glaucomatous eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. METHODS One eye from each subject was scanned with a 68 kHz Cirrus 5000 HD-OCT-based OMAG prototype system centered at the ONH (Carl Zeiss Meditec Inc, Dublin, CA, USA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. En face OMAG images for preLC were generated using signals with highest blood flow signal intensity. ONH perfusion was quantified as flux, vessel area density, and normalized flux within the ONH. Standard t-tests were performed to analyze the ONH perfusion differences between normal and glaucomatous eyes. Linear regression models were constructed to analyze the correlation between ONH perfusion and other clinical measurements. RESULTS Twenty normal and 21 glaucoma subjects were enrolled. Glaucomatous eyes had significantly lower ONH perfusion in preLC in all three perfusion metrics compared to normal eyes (P≤0.0003). Significant correlations between ONH perfusion and disease severity as well as structural changes were detected in glaucomatous eyes (P≤0.012). CONCLUSIONS ONH perfusion detected by OMAG showed significant differences between glaucoma and normal controls and was significantly correlated with disease severity and structural defects in glaucomatous eyes. ONH perfusion measurement using OMAG may provide useful information for detection and monitoring of glaucoma.
T-bet:Eomes Balance, Effector Function, and Proliferation of Cytomegalovirus-Specific CD8+ T Cells during Primary Infection Differentiates the Capacity for Durable Immune Control

CMV remains an important opportunistic pathogen in solid organ transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor+/recipient−; D+R−) are at high-risk for active CMV infection and increased mortality, however the immune correlates of viral control remain incompletely understood. We prospectively studied 23 D+R− LTRs during primary CMV infection to determine whether acute CD8+ T cell parameters differentiated the capacity for viral control in early chronic infection. T-box transcription factors expression patterns of T-bet > Eomesodermin (Eomes) differentiated LTR controllers from viremic relapsers and reciprocally correlated with granzyme B loading, and CMV phosphoprotein 65 (pp65)–specific CD8+IFN-γ+ and CD107a+ frequencies. LTR relapsers demonstrated reduced CD8+Ki67+ cells ex vivo and substantially impaired CD8+pp65-specific in vitro proliferative responses at 6 d, with concomitantly lower pp65-specific CD4+IL-2+ frequencies, as compared with LTR controllers. However, CMV-specific in vitro proliferative responses could be significantly rescued, most effectively with pp65 Ag and exogenous IL-2, resulting in an increased T-bet:Eomes balance, and enhanced effector function. Using class I CMV tetramers, we observed similar frequencies between relapsers and controllers, although reduced T-bet:Eomes balance in tetramer+ cells from relapsers, along with impaired CD8+ effector responses to tetramer-peptide restimulation. Taken together, these data show impaired CMV-specific CD8+ effector responses is not for complete lack of CMV-specific cells but rather underscores the importance of the T-bet:Eomes balance, with CMV-specific proliferation a key factor driving early T-bet expression and effector function in CD8+ T cells during primary infection and differentiating the capacity of high-risk LTRs to establish immune control during early chronic infection.
Okuma Çemberleri: Niçin ve Nasıl? Örnek Bir Uygulama

Okuma cemberleri, ayni oyku, siir ya da kitabi okumak icin bir araya gelen ogrencilerin olusturduklari gruplardir. Bu gruplarda ogrenciler, okuduklarini tartismakta ve paylasmaktadirlar. Gruplarda ustlendikleri rollerin geregi olarak ogrenciler, okuma cemberlerinde pek cok etkinlik yapmaktadirlar. Bu roller, temel ve secimlik roller olmak uzere iki grupta toplanabilir. Temel roller, sorgulayici, bag kurucu, okuma aydinlaticisi, ressamdir. Secimlik roller ise ozetleyici, sozcuk avcisi, hareket izcisi, karakter cozumleyici ve tahmin edici gibi rollerdir. Her ogrenci bir rol almak zorundadir. Rollerin geregi olarak yapilan isler, ogrencilerin bilissel, duyussal ve sosyal yonlerinin gelisimini saglamaktadir. Yapilan her okuma cemberinde ogrenciler ve roller farklilasmaktadir. Boylece farkli rolleri deneyimleyen ogrenciler okuma calismalarindan ust duzeyde verim elde edebilmektedirler. Okuma cemberlerinin nasil yurutuldugune iliskin adim adim sunulan ornek bir uygulamanin, siniflarinda ogrenci merkezli yontemleri kullanmak isteyen ogretmenlere katkilar sunmasi beklenmektedir.
Why illness perceptions matter.

Untreated depression in patients with physical illness causes distress, amplifies physical symptoms and is more predic-tive of functional impairment over time than severity of physical illness. For example, patients with rheumatoid arthritis who become depressed may present with increasingly painful joints in the absence of increased disease activity. Also, diabetic patients with depression have worse glucose control and are more likely to have diabetic complications. It is therefore important that all clinicians should be aware of the frequency of depression in physical illness, be able to recognise it and have an understanding of its management.Are you depressed? ' Screening for depression in the terminally ill. A et al. Long-term medical conditions and major depression: strength of association for specific conditions in the general population. A systematic review of the treatment of depression with antidepres-sant drugs in patients who also have a physical illness. When patients are diagnosed with an illness they generally develop an organ-ised pattern of beliefs about their condition. These views are key determinants of behaviour directed at managing illness. It is a dynamic process which changes in response to shifts in patients' perceptions and ideas about their illness. These illness perceptions or cognitive representations directly influence the individual's emotional response to the illness and their coping behaviour such as adherence to treatment. Despite their importance , patients' views of their illness or symptoms are rarely sought in medical interviews and patients tend not to bring up their illness beliefs with doctors. This paper discusses why illness perceptions matter and how a greater awareness of patients' beliefs can improve both communication in medical consultations and also illness outcomes. When faced with a new health threat such as a new symptom or diagnosis, individuals will actively build cognitive models of this threat and this mental representation will determine how they respond. 1 These models are based on their own medical knowledge or from personal experience of others such as family members with similar symptoms or diagnoses. The patient's model of his or her illness will guide the patient to reduce the danger of the symptoms or illness and simultaneously to guide coping strategies designed to reduce the emotional response to the threat. Researchers have noticed that there is often a symmetry between bodily symptoms and illness labels. 2 When patients have symptoms there is a pressure for them to find a label or explanation for their ill health. Conversely, when …
PROGRESS IN UREMIC TOXIN RESEARCH: The Role of Oxidative Stress in Chronic Kidney Disease

New, reliable circulating oxidative stress markers have become available in chronic kidney disease (CKD) patients and have confirmed the long held belief that CKD is a pro‐oxidant state. However, several questions related to this state of oxidative stress remain largely unresolved. First, the relative importance of each type of oxidant involved has been insufficiently evaluated. Only two recent studies have addressed this issue, and both suggested that chlorinated stress played a central role. Second, as only few population‐based studies are available, the prevalence of oxidative stress among CKD patients remains undetermined. Third, although the link between oxidative stress and inflammation in CKD is emerging as a key process contributing to the genesis of oxidative stress in these patients, its pathogenesis remains poorly defined. Fourth, data favoring the involvement of oxidative stress in uremic toxicity are still limited. Finally, while two recent pilot studies have demonstrated that treatment of CKD patients with antioxidants is able to reduce cardiovascular events, information related to the pharmacokinetic characteristics of antioxidants, as well as their efficacy to prevent oxidative stress, is still limited in this patient group. Thus, although existing data suggest a prominent role of CKD‐associated oxidative stress in uremic toxicity, further studies are required to definitively prove this concept.
Correlation between the Level of Physical Activity as Measured by Accelerometer and the Harris Hip Score

Background The most widely used method to assess the outcome of total hip arthroplasty (THA) is the Harris Hip Score (HHS). Patients’ expectations about the benefits of hip arthroplasty are increasing and are no longer limited to pain reduction. Patients believe they will be able to do recreational activity and sport after surgery. It is also essential to assess the level of physical activity after arthroplasty insofar as it is associated with early failure of the components. The purpose of this study is to explore correlation of the HHS with physical activity in patients with THA. Methods This is a cross-sectional study on 47 patients with THA. Correlation of HHS with the results of physical activity obtained objectively using accelerometer worn for a week and subjectively using the IPAQ questionnaire and the UCLA scale. Finding There was no correlation between the HHS and the activity measured using accelerometers, or with the IPAQ activity questionnaire. The HHS reported moderately significant correlations with the UCLA scale. Conclusions The HHS may not be as discriminatory as other instruments at assessing patient activity levels after THA.
Robust and Nonrobust Path Delay Fault Simulation by Parallel Processing of Patterns

An accelerated fault simulation approach for path delay faults is presented. The distinct features of the proposed fault simulation method consist in the application of parallel processing of patterns at all stages of the calculation procedure, its versatility to account for both robust and nonrobust decision of path delay faults, and its capability of efficiently maintaining large numbers of path faults to be simulated. >
Second-Hand Tobacco Smoke and Allergens – Double Jeopardy for Childhood Asthma Exacerbations

In this issue of Respiration, Dong et al. [4] report findings from a large cohort of 8,819 children (mean age = 4.7 years) sampled randomly from households based in 25 districts of Northeast China. They looked at different forms of respiratory symptoms: from persistent phlegm to current asthma, and from wheeze to doctor-diagnosed asthma both independently and then combined in the presence of childhood allergen and SHS exposure. The findings suggest that current exposure (allergen/SHS) had little or no effect on most of the respiratory symptoms studied. In contrast, in utero and post-natal ( 2 years) allergen/SHS exposures were significant risk factors. However, in the presence of allergens, current SHS exposure showed a significant increased risk of doctordiagnosed asthma although such modified effects were greatest when children had either in utero or post-natal SHS exposures. The present cross-sectional study has both strengths and limitations. Given the complexities of diagnosing childhood asthma and self-reported asthma and asthmalike symptoms, Dong et al. [4] took advantage of a large cohort to report such an association. To the best of our knowledge, no similar studies utilizing such a large cohort of children have yet been reported from any western country. Self-reported data could introduce both misclasAsthma is increasingly being considered a syndrome complex. The mechanistic pathway of asthma is still under exploration. Epidemiological studies, with all their inherent limitations, may provide important insights into causal relationships of a disease. The 2006 US Surgeon General’s Report had inferred a causal relationship of asthma and second-hand tobacco smoke (SHS) exposure [1] . There is no safe free level of SHS, which is also classified as a group 1 carcinogen [2] . Four thousand toxic chemicals constitute tobacco smoke. Steady increases in regional and national smoke-free policies are noted, especially in western societies. But the most vulnerable in society, the children, are silently and involuntarily being exposed to this deadly poison of tobacco smoke. The two most common settings in western society where children are exposed to SHS are in their homes or while travelling by private motor vehicles. The recent UK Royal College of Physicians (RCP) report indicated a 2-fold increased risk of childhood asthma with SHS exposure at home based on meta-analyses of 70 studies [3] . The estimates of childhood asthma vary depending on the type of SHS exposure: in utero or post-natal. Information on acute exacerbations of childhood asthma attributed to SHS (in utero/post-natal) in the presence of childhood exposure to allergens is, however, limited. Published online: December 30, 2010
Relations between relative mRNA abundance and developmental competence of ovine oocytes

The present study was conducted to investigate the relation between in vitro developmental competence and the expression of a panel of developmentally important genes in germinal vesicle (GV) stage oocytes. One‐month‐old prepubertal and adult sheep oocytes were used as models of low and high quality gametes, respectively. Cumulus‐oocyte complexes (COCs) derived from lambs and ewes were in vitro matured and fertilized, and their cleavage rate at 22, 26, and 32 hr post fertilization and the blastocyst yield were observed to assess their developmental potential. In parallel, the relative abundance (RA) of 11 genes was analyzed by semi‐quantitative Reverse Transcription Polymerase Chain Reaction (RT‐PCR) assay in the two groups of oocytes. We observed similar maturation and fertilization rates in the two groups, but a significant lower rate of cleaved prepubertal oocytes (P < 0.05), a general delay in the timing of their first division (P < 0.01), and a lower blastocysts production (P < 0.05). The analysis of gene expression evidenced no difference in the RA of four transcripts [superoxide dismutase (SOD), ubiquitin, β‐actin, cyclin B] in the two classes of oocytes, but a statistically lower RA of seven messenger RNAs (mRNA) [Na+K+ATPase, p34cdc2, Glucose‐transporter I (Glut‐1), Activin, Zona Occludens Protein 2 (PanZO2), Poli(A)Polymerase (PAP), E‐Cadherin (E‐Cad)] in the prepubertal oocytes compared to the adult ones. The present data show for the first time in the ovine species that the lower developmental competence is associated with deficiencies in the mRNAs storage during the oocyte growth. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Effects of Mycophenolic Acid on Human Fibroblast Proliferation, Migration and Adhesion In Vitro and In Vivo

Mycophenolic acid (MPA) is a potent inhibitor of the inosine monophosphate dehydrogenase and used as an immunosuppressive drug in transplantation. MPA inhibits proliferation of T‐ and B‐lymphocytes by guanosine depletion. Since fibroblasts rely on the de novo synthesis of guanosine nucleotides, it is assumed that MPA interacts with fibroblasts causing an increased frequency of wound healing problems. We show a downregulation of the cytoskeletal proteins vinculin, actin and tubulin in fibroblasts exposed to pharmacological doses of MPA using microarray technology, real‐time polymerase chain reaction (PCR) and Western blot. This reduction in RNA and protein content is accompanied by a substantial rearrangement of the cytoskeleton in MPA‐treated fibroblasts as documented by immunofluorescence. The dysfunctional fibroblast growth was validated by scratch test documenting impaired migrational capacity. In contrast, cell adhesion was increased in MPA‐treated fibroblasts. The results of the cultured human fibroblasts were applied to skin biopsies of renal transplant recipients. Skin biopsies of patients treated with MPA expressed less vinculin, actin and tubulin as compared to control biopsies that could explain potential wound healing problems posttransplantation. The perspective of MPA‐induced cytoskeletal dysfunction may go beyond wound healing disturbances and may have beneficial effects on (renal) allografts with respect to scarring.
Janus kinase 3: a novel target for selective transplant immunosupression

Existing immunosuppressants inhibit lymphocyte activation and T cell cytokine signal transduction pathways, reducing the rate of acute rejection episodes to < 10%. However, the widespread tissue distribution of their molecular targets engenders pleiotropic toxicities. One strategy to address this problem seeks to identify compounds that selectively inhibit a target restricted in distribution to the lymphoid system. Janus kinase (Jak) 3 is such a molecule; it mediates signal transduction via the gamma common chain of lymphokine surface receptors. Disruption of this lymphoid-restricted enzyme would not be predicted to produce collateral damage in other organ systems. Development of selective Jak3 inhibitors has been difficult due to crossreactivity with its homologue, Jak2. In contrast to all other putative antagonists, which are discussed in detail herein, one Jak3 inhibitor, NC1153, shows at least 40-fold greater selective inhibition for Jak3 than for Jak2, is robustly synergistic with calcineurin antagonists, and, either alone or in combination with cyclosporin, produces no adverse effects in rodents preconditioned to be at heightened risk for nephrotoxicity, bone marrow suppression, or altered lipid metabolism.
Women with diabetes have poorer control of blood pressure than men.

OBJECTIVE Diabetes is associated with a higher coronary heart disease (CHD) mortality in women compared with men. Less aggressive control of the CHD risk factors in women can contribute to this excess mortality. Because hypertension has a high prevalence in subjects with diabetes, we compared the control of this risk factor between men and women. METHODS This was a retrospective cohort study comparing blood pressure levels and trends over a 1-year period between men and women with diabetes receiving primary care. Using a chronic disease registry database, subjects with type 1 and type 2 diabetes, aged >or=18, were identified for inclusion. Mean weighted systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated for subjects with multiple longitudinal readings. Subjects were classified into four blood pressure control categories based on the mean weighted blood pressure. Comparisons were made between men and women before and after controlling for baseline characteristics. RESULTS A total of 3181 subjects (46% women) were included in the study. More women than men were in the moderate and severely elevated blood pressure categories (40% and 6% compared with 32% and 5%, respectively, p<0.001). The unadjusted mean SBP was 3 mm Hg higher in women (139 mm Hg in women compared with 136 in men, p<0.001). These differences remained significant after controlling for baseline variables. CONCLUSIONS In subjects with diabetes receiving medical care, women had poorer control of blood pressure and a significantly higher mean SBP compared with men. These findings might partially explain the excess CHD mortality in women with diabetes.