Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension

Objective To determine whether outcomes differed for women with pre-eclampsia according to the presence of proteinuria and whether non-proteinuric pre-eclampsia is similar to gestational hypertension. Design From 1987 to 2005, at three hospitals in Sydney, Australia, women referred to the obstetric medicine team were recruited. Outcomes for three groups were compared: proteinuric pre-eclampsia, non-proteinuric pre-eclampsia and gestational hypertension. Results Women with proteinuric pre-eclampsia were more likely to have severe hypertension (39 versus 30%, P = 0.003), deliver preterm infants (39 versus 30%, P = 0.007) and had a higher perinatal mortality rate (25.2 versus 5.7 per 1000, P = 0.02) than those with non-proteinuric pre-eclampsia, who were more likely to have thrombocytopenia and liver disease. Women with non-proteinuric pre-eclampsia were more likely to have multiple pregnancies (3.9 versus 9.9%, P < 0.001), experience severe hypertension (8.9 versus 29.7%, P < 0.001), and deliver preterm infants (11.3 versus 30.2%, P < 0.001) who were small for gestational age (12.7 versus 20.9%, P < 0.001) than those with gestational hypertension. Conclusion This study highlights differences between non-proteinuric pre-eclampsia and gestational hypertension. The subclassification of ‘non-proteinuric pre-eclampsia’ should be added to existing classification systems to alert clinicians to potential risks.
Hoxa-9 Represses Transforming Growth Factor-β-induced Osteopontin Gene Transcription*

Smad2 and Smad3 are downstream transforming growth factor-β (TGF-β) signaling molecules. Upon phosphorylation by its type I receptor, Smad2 or Smad3 forms a complex with Smad4 and translocates to the nucleus where the complex activates target gene transcription. In the present study, we report that Smad3 binds directly to the osteopontin (OPN) promoter and that Smad4 interacts with the Hox protein and displaces it from its cognate DNA binding site in response to TGF-β stimulation. In gel shift assays, the glutathione S-transferase-Smad3 fusion protein was found to bind to a 50-base pair DNA element (−179 to −229) from the OPN promoter. Also, we found that both Hoxc-8 and Hoxa-9 bound to a Hox binding site adjacent to Smad3 binding sequence. Interestingly, Smad4, the common partner for both bone morphogenic protein and TGF-β signaling pathways, inhibited the binding of Hox protein to DNA. FLAG-tagged Smad4 coimmunoprecipitated with HA-tagged Hoxa-9 from cotransfected COS-1 cells, demonstrating an interaction between Smad4 and Hoxa-9. Transfection studies showed that Hoxa-9 is a strong transcriptional repressor; it suppresses the transcription of the luciferase reporter gene driven by a 124-base pair OPN promoter fragment containing both Smad3 and Hox binding sites. Taken together, these data demonstrate a unique TGF-β-induced transcription mechanism. Smad3 and Smad4 exhibit different functions in activation of OPN transcription. Smad3 binds directly to the OPN promoter as a sequence-specific activator, and Smad4 displaces the transcription repressor, Hoxa-9, by formation of Smad4/Hox complex as part of the transcription mechanism in response to TGF-β stimulation.
Analytical performance of a new one-step quantitative prostate-specific antigen assay, the FREND™ PSA Plus

Abstract Background: We evaluated the analytical performance of a new one-step rapid quantitative sandwich immunoassay for total prostate-specific antigen (tPSA), the FREND™ PSA Plus (FREND PSA) (NanoEnTek Inc., Seoul, Korea). Methods: The imprecision, linearity, hook effect, detection limit (LoD), and interference were evaluated and trueness verification and matrix validation were performed. For method comparison, 79 patient specimens were analyzed with FREND PSA and two comparative tPSA assays (Architect® total PSA and cobas® total PSA assay). Results: Total CVs of the imprecision for low (0.208 ng/mL), medium (4.051 ng/mL), and high PSA levels (5.469 ng/mL) were 15.9%, 6.4%, and 9.1%, respectively. Linearity was observed from 1.01 to 19.15 ng/mL and the hook phenomenon was absent up to 171.48 ng/mL. The LoD was 0.094 ng/mL. The regression equations between FREND (y) and Architect or cobas were as follows: y=0.0133+1.054x (r=0.973), y=–0.2144+1.066x (r=0.977), respectively. Differences between FREND PSA and the comparative methods at a medical decision level of 4.0 ng/mL were less than the optimum specification bias (9.3%). The percentage biases from the trueness verification and interference test were less than the desirable specifications for bias (18.7%). The plasma tPSA level measured with lithium heparin or K2EDTA was comparable to that in the serum. Conclusions: The FREND PSA provided reliable analytical performance and test results in comparison to two widely used tPSA assays. It is a simple and rapid test for tPSA and can be applied in point-of-care testing.
Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease Undergoing Computed Tomography: A Double-Blind Comparison of Iodixanol and Iopamidol

Background:Based on a single clinical trial, it has been suggested that the contrast agent iodixanol, which is isotonic to human plasma, may be less nephrotoxic than other nonionic contrast agents in renally impaired patients after intra-arterial injection. We compared the effects on renal function of iopamidol-370 injection (796 mOsm/kg) and iodixanol-320 (290 mOsm/kg) in patients with chronic kidney disease undergoing contrast-enhanced multidetector computed tomography (CE-MDCT) examinations using a multicenter, double-blind, randomized, parallel-group design. Methods:A total of 166 patients with stable moderate-to-severe chronic kidney disease (screening and baseline serum creatinine, SCr, ≥1.5 mg/dL and/or creatinine clearance, CrCl, ≤60 mL/min) who were undergoing CE-MDCT of the liver or peripheral arteries were randomized to receive equi-iodine IV doses (40 gI) of either iopamidol-370 (370 mgI/mL) or iodixanol-320 (320 mgI/mL) at 4 mL/s. SCr and CrCl were obtained at screening, baseline, and at 48–72 ± 6 hours after dose (mean, 57.4 hours). Contrast-induced nephropathy (CIN) was defined as an absolute increase ≥0.5 mg/dL (44.2 &mgr;mol/L) and/or a relative increase in SCr ≥25% from baseline. Results:A total of 153 patients were included in the final analysis (13 patients excluded because of lack of follow-up, hemodialysis to remove contrast, average daily CrCl variation >1% at screening). The 2 study groups were comparable with regard to age, gender distribution, the presence of diabetes, concomitant medications, hydration, and contrast dose. Mean predose SCr was 1.6 ± 0.4 mg/dL in both groups (P = 0.9). An absolute increase ≥0.5 mg/dL (44.2 &mgr;mol/L) in SCr was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76) of patients receiving iodixanol-320 (95% confidence interval −6.2, 1.0, P = 0.2). A relative increase ≥25% in SCr occurred in 4% (3/77) of patients receiving iopamidol-370 and in 4% (3/76) of the patients receiving iodixanol-320 (95% confidence interval −6.2, 6.1, P = 1.0). Conclusion:The rate of CIN was similarly low in risk patients after intravenous administration of iopamidol-370 or iodixanol-320 for CE-MDCT.
ROLE OF NEUTROPHIL ELASTASE IN DEVELOPMENT OF PULMONARY VASCULAR INJURY AND SEPTIC SHOCK IN RATS

Prostacyclin prevents pulmonary vascular injury and shock by inhibiting increases in lung tissue levels of TNF in rats administered endotoxin. We previously reported that NO derived from eNOS increases endothelial production of prostacyclin. Because neutrophil elastase has been shown to decrease endothelial production of prostacyclin by inhibiting NOS activity, we examined whether neutrophil elastase inhibitors reduce pulmonary vascular injury and hypotension by inhibiting the decrease in pulmonary endothelial production of prostacyclin in rats administered endotoxin. Animals were pretreated with sivelestat or L-658,758, neutrophil elastase inhibitors, before endotoxin administration. Lung tissue levels of 6-keto-prostaglandin F1&agr; were markedly increased after endotoxin administration, followed by a rapid decrease to baseline levels. Sivelestat and L-658,758 inhibited these decreases as well as inhibiting increases in lung tissue levels of TNF and lung wet-to-dry weight ratios in animals administered endotoxin. These inhibitors also reduced hypotension and inhibited increases in lung tissue levels of mRNA of the inducible form of NOS in animals administered endotoxin. The effects of neutrophil elastase inhibitors were completely reversed by pretreatment with nitro-l-arginine methyl ester, an inhibitor of NOS, or indomethacin, a nonspecific cyclooxygenase inhibitor. These observations suggested that neutrophil elastase might decrease the pulmonary endothelial production of prostacyclin by inhibiting endothelial NO production, thereby contributing to the development of pulmonary vascular injury and shock through increases in lung tissue levels of TNF in rats administered endotoxin.
Pulmonary artery distensibility in pulmonary arterial hypertension: an MRI pilot study

Pulmonary arterial hypertension (PAH) is a disease of the small vessels in which there is a substantial increase in pulmonary vascular resistance leading to right ventricle failure and death. Invasive haemodynamic evaluation is mandatory not only for diagnosis confirmation but also to address prognosis and eligibility for the use of calcium-channel blockers through an acute vasodilator challenge. Noninvasive surrogate response markers to the acute vasodilator test have been sought. In the present study, the relationship between pulmonary artery distensibility, assessed using magnetic resonance imaging (MRI), and response to acute vasodilator tests was investigated. In total, 19 patients diagnosed with idiopathic PAH without any specific treatment were evaluated. Within a 48-h window after pulmonary artery catheterisation, patients underwent cardiac MRI. Cardiac index, calculated after the determination (invasively and noninvasively) of cardiac output, showed excellent correlation, as did right atrial pressure and right ventricle ejection fraction. Pulmonary artery distensibility was significantly higher in responders. A receiver operating characteristic curve analysis has shown that 10% distensibility was able to differentiate responders from nonresponders with 100% sensitivity and 56% specificity. The present findings suggest that magnetic resonance imaging and pulmonary artery distensibility may be useful noninvasive tools for the evaluation of patients with pulmonary hypertension.
Flow Rate Calibration for Absolute Cell Counting Rationale and Design

There is a need for absolute leukocyte enumeration in the clinical setting, and accurate, reliable (and affordable) technology to determine absolute leukocyte counts has been developed. Such technology includes single platform and dual platform approaches. Derivations of these counts commonly incorporate the addition of a known number of latex microsphere beads to a blood sample, although it has been suggested that the addition of beads to a sample may only be required to act as an internal quality control procedure for assessing the pipetting error. This unit provides the technical details for undertaking flow rate calibration that obviates the need to add reference beads to each sample. It is envisaged that this report will provide the basis for subsequent clinical evaluations of this novel approach.
Design, Fabrication, and Measurement of a One-Dimensional Periodically Structured Surface Antenna

A radiating periodically structured surface resonator is studied from the point of view of minimizing the radiation Q-factor of the fundamental mode of the resonator. Structures with a one-dimensional array of gaps are considered, where the resonant mode is formed by the capacitance of the gaps resonating with the inductance of the conducting pathways. An eigenmode study of a range of designs of identical size demonstrates that increasing the number of gaps does not lower the Q . The results show that this family of resonators has a radiation Q that is typically ~ 2 &times; lower than a simple patch antenna occupying the same electrical volume. The improvement in Q is accompanied by a corresponding reduction in the directivity gain of the broadside radiation, confirming the inherent bandwidth/directivity trade-off in radiators of identical size and shape. A three-period resonator is made into an antenna by driving it from underneath the surface. The fabricated antenna has dimensions of 0.40 λ × 0.26 λ, a thickness of λ/34, and a measured 10 dB return loss bandwidth of 12.4%, ~ 4.5 &times; wider than a simple patch antenna of the same size. These antennas can replace patch antennas in applications demanding the widest possible impedance bandwidth from a thin antenna.
Phagocytosis and Protein Processing Are Required for Presentation of Cryptococcus neoformans Mitogen to T Lymphocytes

ABSTRACT In addition to eliciting antigen specific T-cell-mediated immunity,Cryptococcus neoformans possesses a mitogen (CnM) that activates naive T cells to proliferate. This mechanism of T-cell activation is accessory cell dependent and major histocompatibility complex unrestricted. CnM-induced T-cell proliferation correlates with internalization of the organism, suggesting that intracellular processing is required to liberate CnM prior to presentation to T cells. To determine whether phagocytosis and processing are required, various inhibitors of accessory cell uptake and processing were used.C. neoformans was observed within the accessory cells. Paraformaldehyde fixation of the accessory cell abrogated presentation of CnM to T cells, indicating that a dynamic accessory cell surface was required. A lysosomotropic agent abrogated the response to CnM but had no effect on a control stimulus that did not require processing. Both aspartic acid and cysteine protease inhibitors blocked effective processing of CnM, so that it was unable to stimulate T cells. Finally, an inhibitor of microfilament polymerization abrogated proliferation to CnM. These results indicate that the mitogenic activity of C. neoformans requires phagocytosis of the organism, lysosomal or endosomal processing, proteolytic activity, and microfilament polymerization and intracellular transport as a prerequisite for T-cell proliferation.
Extracellular matrix and hormones modulate DAX-1 localization in the human fetal adrenal gland.

CONTEXT The orphan nuclear receptor DAX-1 is essential for human adrenal cortex development and functions as a transcriptional repressor of multiple genes implicated in steroidogenic pathways. OBJECTIVE The aim of this study was to investigate the localization of the DAX-1 protein in human fetal adrenal glands and to assess whether this protein can be modulated by the extracellular matrix and hormones. RESULTS DAX-1 is localized mainly in the nucleus in the outer definitive zone and in the cytoplasm in the fetal zone, whereas the number of DAX-1 positive cells decreases from the external to the internal portion of the gland. When cultured on a collagen or a fibronectin matrix, DAX-1 is localized in the nucleus of the definitive cells and exhibits a nucleocytoplasmic distribution in the fetal cells. ACTH stimulation induces nuclear localization of DAX-1 in fetal cells cultured on collagen without modifying nucleocytoplasmic localization on fibronectin. In contrast, angiotensin II induces the protein to be localized only in the cytoplasm in fetal cells cultured on either collagen or fibronectin. CONCLUSIONS The localization of DAX-1 is compatible with the known functional properties of DAX-1 regarding the steroidogenic activity of adrenal cells. Moreover, this study suggests that modulation of DAX-1 localization in the fetal adrenal gland by hormones and components of the extracellular matrix may represent a mechanism for controlling the expression of steroidogenic enzymes in the definitive and fetal zones.
Childhood traumatization by primary caretaker and affect dysregulation in patients with borderline personality disorder and somatoform disorder

Affect regulation is often compromised as a result of early life interpersonal traumatization and disruption in caregiving relationships like in situations where the caretaker is emotionally, sexually or physically abusing the child. Prior studies suggest a clear relationship between early childhood attachment-related psychological trauma and affect dysregulation. We evaluated the relationship of retrospectively recalled childhood traumatization by primary caretaker(s) (TPC) and affect dysregulation in 472 adult psychiatric patients diagnosed with borderline personality disorder (BPD), somatoform disorder (SoD), both BPD and SoD, or disorders other than BPD or SoD, using the Bermond-Vorst Alexithymia Questionnaire, the self-report version of the Structured Interview for Disorders of Extreme Stress, the Self-rating Inventory for Posttraumatic Stress Disorder (SRIP) and the Traumatic Experiences Checklist. Almost two-thirds of participants reported having experienced childhood TPC, ranging from approximately 50% of patients with SoD or other psychiatric disorders to more than 75% of patients with comorbid BPD+SoD. Underregulation of affect was associated with emotional TPC and TPC occurring in developmental epoch 0–6 years. Over-regulation of affect was associated with physical TPC. Childhood trauma by a primary caretaker is prevalent among psychiatric patients, particularly those with BPD, and differentially associated with underand over-regulation of affect depending on the type of traumatic exposure.
Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta‐analysis

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta‐analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%‐34.4%; N = 198; n = 52,678). Relative risk meta‐analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta‐analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = −3.6, p = 0.0003, r2 = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic‐naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35‐1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.
Low Cognitive Status Is Associated with a Lower Ability to Maintain Standing Balance in Elderly Outpatients

Background: Evidence is emerging that cognitive performance is involved in maintaining balance and thereby involved in falls in the elderly. Objective: To investigate the association of cognitive status with measures of standing balance in elderly outpatients. Methods: In a cross-sectional study, 197 community-dwelling elderly [mean age (SD) 81.9 (7.1) years] referred to a geriatric outpatient clinic were included and subsequently dichotomized into a group with low and normal cognitive status based on cut-off values of the Mini-Mental State Examination, Montreal Cognitive Assessment and Visual Association Test. The ability to maintain standing balance as well as the center of pressure (CoP) movement were assessed during 10 s of side-by-side, semi-tandem and tandem stance with eyes open and eyes closed. Logistic and linear regression were used to examine the association between cognitive status and measures of standing balance adjusted for age, gender and highest completed education. Results: Low cognitive status in elderly outpatients was associated with a lower ability to maintain 10 s of balance in side-by-side stance with eyes closed [OR (95% CI): 3.57 (1.60; 7.97)] and in semi-tandem stance with eyes open and eyes closed [OR (95% CI): 3.93 (1.71; 9.00) and OR (95% CI): 2.32 (1.11; 4.82), respectively]. Cognitive status was not associated with CoP movement. Conclusion: Low cognitive status associates with a lower ability to maintain standing balance in more demanding standing conditions in elderly outpatients. This may have implications for routine geriatric screening strategies and interpretation of results of either standing balance or cognitive tests.