Miracle-dz/UniFAR-FTUs huggingface dataset:
The usefulness of combined biochemical tests in the diagnosis of Cushing's disease with negative pituitary magnetic resonance imaging.

OBJECTIVE The etiological diagnosis of ACTH-dependent Cushing's syndrome is often a problem. In fact, no endocrine or radiological examination can conclusively distinguish the ectopic from the pituitary source of disease. The aim of our study was to evaluate the role of stimulation and suppression endocrine tests in the diagnostic and therapeutic approach of patients with Cushing's disease (CD) and negative pituitary magnetic resonance imaging (MRI), considering their post-surgical outcome in comparison with patients with CD and positive MRI. PATIENTS AND METHODS We retrospectively analyzed 31 patients (25 women and 6 men, median age 40 +/- 15 years) with a confirmed diagnosis of CD who underwent transsphenoidal pituitary surgery by the same neurosurgeon between 2001 and 2005. Preoperative endocrine assessment included corticotropin-releasing hormone (CRH), desmopressin (dDAVP), and overnight 8 mg dexamethasone suppression tests (8-DST) in all patients. Fifteen patients had a normal pituitary MRI and sixteen had a clearly evident pituitary microadenoma. Bilateral inferior petrosal sinus sampling (BIPSS) was performed in patients with discordant biochemical results or with signs and symptoms highly suggestive of an ectopic source of ACTH. Post-surgical median follow-up was 38.4 +/- 22.0 months. RESULTS Among patients with negative MRI, 60% had concordant positive endocrine tests and underwent neurosurgery without other examinations. BIPSS was performed in three other patients prompted by discordant endocrine tests (negative dDAVP) and in two patients with clinical suspicion of ectopic disease. Among patients with positive MRI, 87% underwent neurosurgery without BIPSS that was performed in two patients because of negative concomitant response to dDAVP and CRH tests. A pituitary adenoma, confirmed by pathological examination, was found in 40 and 81% of patients with negative and positive MRI respectively (P<0.05), corticotroph hyperplasia resulted more frequent in the group with negative MRI. Remission rate was not different between patients with negative and positive MRI (73 and 75% respectively; P=0.61) and between patients with negative MRI who did not undergo BIPSS and patients with positive MRI (P=0.56). The recurrence rate was also similar between groups (P=0.64), but higher, although not statistically different (P=0.07) in patients with corticotroph hyperplasia at histology. CONCLUSIONS An accurate evaluation of presurgical endocrine tests results enabled us to reduce the number of BIPSS in patients with a negative MRI without any fallout on their post-surgical outcome. In the hands of an expert pituitary surgeon, the outcome after surgeryand the subsequent recurrence rate are much the same in patients with negative or positive MRI.
In Vitro Growth of Preantral Follicles Isolated from Cryopreserved Ovine Ovarian Tissue

Abstract In the present study, we compared the in vitro development of sheep preantral follicles obtained from unfrozen or frozen ovarian cortex. After thawing, follicles stored by a slow-freezing protocol with dimethyl sulfoxide (DMSO) or ethylene glycol (EG) were mechanically isolated and cultured for 10 days. After 1 day, approximately 50% and 34% of the DMSO and EG follicles, respectively, showed overt signs of degeneration, as confirmed by histological analysis. Follicles that survived thawing grew and formed antral-like cavities, without significant differences among experimental groups. However, the percentages of healthy oocyte-cumulus cell complexes (OCCs) retrieved from in vitro-grown follicles, as well as estradiol, were lower in DMSO than in EG or unfrozen follicles. Although cryopreservation did not cause appreciable differences in follicle morphological aspects, frozen OCCs showed lower metabolic cooperativity levels, as determined by [3H]uridine uptake. During culture, oocytes increased in diameter, but the percentage of germinal vesicle stage-arrested oocytes showing a rimmed chromatin configuration was significantly lower in the frozen groups. Our results indicate that cryopreserved sheep preantral follicles underwent growth in vitro but that freezing/thawing specifically affected gap junctional permeability and impaired the progression of regulative processes, such as the acquisition of a specific oocyte chromatin configuration. Moreover, because the cryoprotectant toxicity test excluded the occurrence of direct cellular damage, this method allowed us to discriminate the effects exerted by different cryoprotectants during the cryopreservation procedure on whole-follicular development.
A Role for Peroxisomes in Photomorphogenesis and Development of Arabidopsis

The nuclear protein DET1 is a central repressor of photomorphogenesis in plants. We have identified the molecular lesion in ted3, a mutation that dominantly suppresses the phenotypes of det1-1. TED3 encodes a peroxisomal protein (AtPex2p) essential for Arabidopsis growth. Developmental defects and the abnormal expression of many genes indet1 are rescued by ted3. ted3 also partially suppresses another pleiotropic de-etiolated mutantcop1. Thus, peroxisomes, whose functions are still largely unexplored, play a key role in a photomorphogenetic pathway negatively regulated by the DET1 and COP proteins.
Behavioural and emotional features in Rett syndrome.

PURPOSE/METHOD There is increasing agreement that many genetic disorders have characteristic behavioural phenotypes; that is genetic anomalies have specific effects on behaviour. In this paper the existing literature is reviewed with an aim to identify behavioural and emotional features that are candidates for Rett syndrome (RS) specific behaviours. RESULT/CONCLUSION A number of behavioural and emotional features have been reported to be common in individuals with RS. These behaviours may constitute an RS-specific profile of behaviour or behavioural phenotype. Alternatively, these behaviours may simply reflect the multiple disabilities found in individuals with severe or profound cognitive impairment. The diagnostic criteria for Rett syndrome include a number of the behavioural features, such as hand stereotypies and breathing difficulties, although other behavioural features are not included.
The Noetic Prism

Definitions of ‘knowledge’ and its relationships with ‘data’ and ‘information’ are varied, inconsistent and often contradictory. In particular the traditional hierarchy of data-information-knowledge and its various revisions do not stand up to close scrutiny. We suggest that the problem lies in a flawed analysis that sees data, information and knowledge as separable concepts that are transformed into one another through processing. We propose instead that we can describe collectively all of the materials of computation as ‘noetica’, and that the terms data, information and knowledge can be reconceptualised as late-binding, purpose-determined aspects of the same body of material. Changes in complexity of noetica occur due to value-adding through the imposition of three different principles: increase in aggregation (granularity), increase in set relatedness (shape), and increase in contextualisation through the formation of networks (scope). We present a new model in which granularity, shape and scope are seen as the three vertices of a triangular prism, and show that all value-adding through computation can be seen as movement within the prism space. We show how the conceptual framework of the noetic prism provides a new and comprehensive analysis of the foundations of computing and information systems, and how it can provide a fresh analysis of many of the common problems in the management of intellectual resources.
Perspectives on the underlying drivers of urgent and emergency care reconfiguration in Ireland

Summary Background There is an increasing tendency to reconfigure acute hospital care towards a more centralised and specialised model, particularly for complex care conditions. Although centralisation is presented as “evidence‐based”, the relevant studies are often challenged by groups which hold perspectives and values beyond those implicit in the literature. This study investigated stakeholder perspectives on the rationale for the reconfiguration of urgent and emergency care in Ireland. Specifically, it considered the hypothesis that individuals from different stakeholder groups would endorse different positions in relation to the motivation for, and goals of, reconfiguration. Methods Documentary analysis of policy documents was used to identify official justifications for change. Semi‐structured interviews with 175 purposively sampled stakeholders explored their perspectives on the rationale for reconfiguration. Results While there was some within‐group variation, internal and external stakeholders generally vocalised different lines of argument. Clinicians and management in the internal stakeholder group proposed arguments in favour of reconfiguration based on efficiency and safety claims. External stakeholders, including hospital campaigners and local political representatives expressed arguments that focused on access to care. A “voter” argument, focused on the role of local politicians in determining the outcome of reconfiguration planning, was mentioned by both internal and external stakeholders, often in a critical fashion. Conclusion Our study adds to an emerging literature on the interaction between a technocratic approach to health system planning advocated by clinicians and health service managers, and the experiential “non‐expert” claims of the public and patients.
Some antiphospholipid antibodies recognize conformational epitopes shared by beta2-glycoprotein I and the homologous catalytic domains of several serine proteases.

OBJECTIVE To test the hypothesis that some antiphospholipid antibodies (aPL) in patients with the antiphospholipid syndrome (APS) recognize a conformational epitope shared by beta2-glycoprotein I (beta2GPI; the major autoantigen for the antiphospholipid antibodies) and the homologous catalytic domains of several serine proteases (such as thrombin, activated protein C [APC], and plasmin) involved in hemostasis. METHODS We generated 4 new IgG monoclonal aPL (2 screened against beta2GPI, 1 against thrombin, and 1 against protein C) from 2 APS patients. The monoclonal antibodies (mAb) were analyzed for binding to beta2GPI, thrombin, APC, and plasmin, as well as for anticardiolipin antibody (aCL) activity. To demonstrate a shared epitope between beta2GPI and a serine protease, 1 mAb was studied by cross-inhibition analysis. RESULTS Both of the IgG anti-beta2GPI mAb bound to thrombin, APC, and plasmin. On the other hand, the 1 anti-thrombin mAb and the 1 anti-protein C mAb also bound to beta2GPI. Moreover, the binding of 1 cross-reactive mAb to beta2GPI was inhibited by alpha-thrombin (which contains only the catalytic domain of thrombin). All 4 mAb displayed aCL activity. CONCLUSION Taken together with the findings that some aCL bind to several serine proteases that participate in hemostasis and share homologous catalytic domains, these data demonstrate that some aCL in APS patients recognize one or more conformational epitopes shared by beta2GPI and the catalytic domains of disease-relevant serine proteases.
Roles of angiopoietin-1 and angiopoietin-2 on airway microvascular permeability in asthmatic patients.

BACKGROUND Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma. METHODS Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 mug/d) or montelukast (10 mg) for 12 weeks. RESULTS VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level. CONCLUSIONS Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.
Adeno-Associated Virus Type 2 Rep78 Induces Apoptosis through Caspase Activation Independently of p53

ABSTRACT Adeno-associated virus (AAV) type 2 Rep78 is a multifunctional protein required for AAV DNA replication, integration, and gene regulation. The biochemical activities of Rep78 have been described, but the effects of Rep proteins on the cell have not been characterized. We have analyzed Rep-mediated cytotoxicity. We demonstrated that Rep78 expression is sufficient to induce cell death and disruption of the cell cycle. Cell death was found to be mediated by apoptosis. Rep78 expression resulted in the activation of caspase-3, a terminal caspase directly involved in the execution of cell death. A peptidic inhibitor of caspase-3, Z-Asp-Glu-Val-Asp-fluoromethylketone (Z-DEVD-FMK), abrogated Rep78-induced apoptosis, indicating that Rep78-mediated apoptosis is caspase-3 dependent. Rep78 induced apoptosis in wild-type p53-containing human embryonal carcinoma NT-2 cells and in p53-null promyelocytic human HL-60 cells, indicating that at least one pathway of Rep78-induced apoptosis is p53 independent. Apoptosis was shown to occur during the G1 and early S phases of the cell cycle. By analyzing the effects of Rep78 mutations on cell viability, the cause of cell death was attributed in part to two biochemical activities of Rep78, DNA binding and ATPase/helicase activity. The endonuclease activity of Rep78 did not contribute to apoptosis induction.
Barriers to Change in the Informed Consent Process: A Systematic Literature Review.

cess for clinical research is one that includes personal interactions, the informed consent document, and an individual’s decision about whether to participate in research. The intent is to enable an individual to make a decision about participation on the basis of a clear understanding of the research, its risks and benefits, and the commitments associated with enrolling in the study. While there is no ideal standard for the informed consent process, we looked at informed consent with the assumption that the consent process should be understandable, that participant satisfaction with the consent process matters, and that a good consent process will improve retention and adherence within a study. An effectively communicative informed consent process may aid recruitment, but the goal should be for potential research participants to make an informed decision, not simply to opt in to a research study. The informed consent process as it currently exists often fails to accomplish these objectives.1 Long and complex informed consent documents and informed consent processes may obscure the information most relevant to the potential research participant and appear to be designed primarily to serve the role of protecting institutions and meeting regulatory needs rather than to inform the potential participant. The proposed revisions to the Common Rule announced in September 2015 suggest that a shorter informed consent document is preferable,2 but a key question is whether such a change will accomplish the objectives described above. Based on the idea that there are opportunities to improve the consent process, the Clinical Trials Transformation Initiative (CTTI) initiated the Informed Consent Project, with objectives to identify and understand existing informed consent improvement efforts, identify barriers to communication of informed consent elements, and develop recommendations for improving the informed consent process that will enhance understanding by potential participants about the study for which they May-June 2016 • VoluMe 38, nuMber 3
Sympathetic nervous function in patients with hypertrophic cardiomyopathy assessed by [123I]-MIBG: relationship with left ventricular perfusion and function.

AIM The aim of the present study was to evaluate [123I] MIBG uptake and clearance in patients with hypertrophic cardiomyopathy (HCM) and to assess their relationships with left ventricular function (systolic and diastolic) and perfusion. METHODS Eleven consecutive patients with HCM (8 men and 3 women; mean age 38+/-12 years, none in the dilated phase) underwent (in separate days, in random order) [123I]-MIBG scintigraphy, [(99m)Tc]-MIBI SPET at rest, and echocardiography. All patients were studied in fasting condition, and all medications were discontinued. [(99m)Tc]-MIBI SPET study was performed 1 hour after tracer injection. [123I]-MIBG study was acquired 5 minutes (planar) and 4 hours (planar and SPET) after the i.v. injection of [123I]-MIBG. Heart to mediastinum ratio (H/M) was computed at 4 hours. Wash out rate (WOR) was computed as: (H early - H delayed)/(H early), after decay correction. Both [123I]-MIBG and [(99m)Tc]-MIBI SPET were analyzed on 3 short axis views (apical, middle, and basal). Left ventricular outflow tract gradient (LVOTG), ejection fraction, volumes, septum thickness, and left atrial fractional shortening (LAFS) were evaluated on echocardiography. RESULTS [123I]-MIBG WOR showed a positive relationship with LVOTG (r=0.84, p<0.001) and septum thickness (r=0.76, p<0.01), while a negative one was found with LAFS (r= -0.66, p<0.05). The study group was divided into: Group A (n=5) with higher, and Group B (n=6) with lower WOR than the median value (i.e. 11%). Group A patients had significantly lower LAFS (17.6+/-4.8 vs 26.8+/-7.2%, p<0.05), higher LVOTG (49+/-35 vs 3+/-3 mmHg), and thicker septum (21+/-2 vs 17+/-2 mm) than Group B patients. Inferior and septal wall [123I]-MIBG uptake on 4 hour SPET was significantly lower in Group A than in Group B. On the other hand, no differences were found in (99m)T-MIBI SPET rest regional uptake between the 2 subgroups of patients. CONCLUSION These results suggest that cardiac sympathetic activity correlates to cardiac anatomy (i.e. degree of hypertrophy) and diastolic function in patients with HCM.
Assessment of Trace Metal Distribution and Contamination In Surface Soils of Al-Waziriya, Baghdad

A total of 100 samples from the top soil were collected from four different zones (tow industrial locations, tow residential locations) located in Al-Waziriya, Baghdad. Soil samples were analyzed for their content of Cd, Cu, Pb and Zn. A profile for average content of these selected metals has been determined by taking average values for different zones. The average concentrations of Cd, Cu, Pb and Zn in the whole area were 11.45, 143.3, 3291.38 and 195.2 mg/kg, respectively. Highest concentrations for selected heavy metals were observed in the industrial area. Enrichment factor calculations indicated that Pb, Cu, Cd and Zn are highly enriched. Battery factories, fossil fuel combustion from traffic emissions, wear of brake lining materials, and several industrial processes are considered as major sources of the studied heavy metals.
Colocated general medical care and preventable hospital admissions for veterans with serious mental illness.

OBJECTIVE This study examined whether veterans with serious mental illness in mental health settings with colocated general medical care had fewer hospitalizations for ambulatory care-sensitive conditions than veterans in other settings. METHODS Using 2007 data, the study examined hospitalizations for ambulatory care-sensitive conditions with zero-inflated negative binomial regression controlling for demographic, clinical, and facility characteristics. RESULTS Of 92,268 veterans with serious mental illness, 9,662 (10.5%) received care at ten sites with colocated care and 82,604 (89.5%) at 98 sites without it. At sites without colocation, 5.1% had a hospitalization for an ambulatory care-sensitive condition, compared with 4.3% at sites with colocation. Attendance at sites with colocated care was associated with an adjusted count of hospitalizations of . 76 compared with attendance at sites with no colocation (β=-.28, 95% confidence interval=.47 to -.09, p=.004). CONCLUSIONS Colocation of general medical services in the mental health setting was associated with significantly fewer preventable hospitalizations.
Familial hypercholesterolemia in northwestern Greece

Introduction: Familial hyperholesterolaemia (FH) is the most common genetic disorder and results from mutations in the low-density lipoprotein receptor (LDLR) gene. So far, over 700 mutations have been reported for the LDLR gene and account for the disease. The nature of LDLR gene mutations is different in various ethnicities and also exhibits regional distribution within each ethnicity. The aim of this study was to identify the LDLR gene mutations causing FH in Northwestern Greece, to find their geographical distribution and, finally, to examine the effect of genetic factors on the lipid profile of these FH patients. Methods: Probands with a clinical diagnosis of FH (n=153) had their DNA tested for mutations in the LDLR gene. Previously published criteria were used for the clinical diagnosis and the genetic analysis was performed either by using restriction enzymes or by DNA sequencing. Apolipoprotein (apo) E gene polymorphism was done using a previously reported protocol. Eight-two normal individuals matched for age, sex, body mass index and smoking habit were used as controls. Results: The clinical diagnosis was genetically confirmed in 123 patients. Nine LDLR gene defects were causing FH in the patients studied; two of them have been described for the first time worldwide (T1352C and g.387_410del24), while three mutations have been isolated for the first time in Greek patients (T81G, G1694T and G1775A). The other responsible mutations were T517C, C858A, G1285A and G1646A. Eight patients were homozygotes for the G1775A mutation, which was the most common mutation encountered in our area (29%) and one was homozygote for the G1646A mutation. The most common mutations exhibit geographical distribution in the area of the Northwestern Greece. Heterozygous FH patients had significantly lower serum HDL cholesterol (HDLC) levels and higher lipoprotein (a) [Lp(a)] levels compared to normal controls. The
Concordant Uptake of Tc‐99m Sestamibi and TI‐201 in Unsuspected Breast Tumor

An unsuspected breast tumor was discovered in a 65-year-old woman referred for evaluation of possible ischemic heart disease. Marked tumor uptake of TI-201 and concordant but less intense uptake of Tc-99m sestamibi (Tc-99m MIBI) was observed after both planar and SPECT imaging post treadmill exercise. Although many reports in the literature document TI-201 tumor uptake, this is much less frequently reported with Tc-99m MIBI at this time. To the authors' knowledge, Tc-99m MIBI breast tumor uptake has not been reported to date. Tc-99m MIBI might prove useful in the detection of primary and meta-static breast carcinoma, and warrants further investigation.