Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of tibolone and its metabolites on vascular endothelial growth factor isoforms 121 and 165 and thrombospondin-1 mRNA in Ishikawa cells

Objective To compare the mRNA expression of vascular endothelial growth factor (VEGF) 121 and 165 isoforms and thrombospondin-1 (TSP-1) after incubation with tibolone and tibolone metabolites 3&agr;-hydroxytibolone, 3&bgr;-hydroxytibolone, &Dgr;4-tibolone, and 17&bgr;-estradiol (E2) in cultured Ishikawa cells. Design Ishikawa cells (immortalized from a well-differentiated human adenocarcinoma cell line) were cultured in vitro to confluence. Tibolone, 3&agr;-hydroxytibolone, 3&bgr;-hydroxytibolone, &Dgr;4-tibolone and E2 at concentrations of 1.0, 0.1 and 0.01 &mgr;mol/L were added to confluent cells and further cultured for an additional 24 h. Control cells were treated with medium in absence of hormone. Total RNA was extracted from control and treated Ishikawa cells. After reverse transcription, VEGF, TSP-1 and the housekeeping gene, &bgr;-actin cDNAs, were amplified in a polymerase chain reaction spiked with 33p-dCTP. Relative abundance of VEGF 121 and 165 isoforms and TSP-1 mRNA was measured by scintillation spectroscopy. Results E2, tibolone, 3&agr;-hydroxytibolone, and 3&bgr;-hydroxytibolone increased both VEGF 121 and 165 mRNA compared with the control. However, &Dgr;4-tibolone had no effect on either VEGF 121 or 165 mRNA compared with the control. &Dgr;4-Tibolone increased TSP-1 mRNA expression compared with control levels. E2, tibolone, 3&agr;-hydroxytibolone, and 3&bgr;-hydroxytibolone did not increase TSP-1 mRNA expression at any concentration. Conclusions Tibolone and the 3&agr;- and 3&bgr;-tibolone metabolites with E2 increased VEGF 121 and 165 isoforms. Conversely, &Dgr;4-tibolone, which is reported to have progestational-like activity, did not stimulate VEGF 121 and VEGF 165 but increased TSP-1 mRNA synthesis in cultured Ishikawa cells. We hypothesize, based on these data, that the clinical finding of no endometrial growth in women using tibolone may be partly related to alterations in these angiogenic factors.
Survival and complication rates of implant-supported fixed partial dentures with cantilevers: a systematic review.

OBJECTIVE The objective of the present systematic review was to analyze the potential effect of incorporation of cantilever extensions on the survival rate of implant-supported fixed partial dental prostheses (FPDPs) and the incidence of technical and biological complications, as reported in longitudinal studies with at least 5 years of follow-up. METHODS A MEDLINE search was conducted up to and including November 2008 for longitudinal studies with a mean follow-up period of at least 5 years. Two reviewers performed screening and data abstraction independently. Prosthesis-based data on survival/failure rate, technical complications (prosthesis-related problems, implant loss) and biological complications (marginal bone loss) were analyzed. RESULTS The search provided 103 titles with abstract. Full-text analysis was performed of 12 articles, out of which three were finally included. Two of the studies had a prospective or retrospective case-control design, whereas the third was a prospective cohort study. The 5-year survival rate of cantilever FPDPs varied between 89.9% and 92.7% (weighted mean 91.9%), with implant fracture as the main cause for failures. The corresponding survival rate for FPDPs without cantilever extensions was 96.3-96.2% (weighted mean 95.8%). Technical complications related to the supra-constructions in the three included studies were reported to occur at a frequency of 13-26% (weighted mean 20.3%) for cantilever FPDPs compared with 0-12% (9.7%) for non-cantilever FPDPs. The most common complications were minor porcelain fractures and bridge-screw loosening. For cantilever FPDPs, the 5-year event-free survival rate varied between 66.7% and 79.2% (weighted mean 71.7%) and between 83.1% and 96.3% (weighted mean 85.9%) for non-cantilever FPDPs. No statistically significant differences were reported with regard to peri-implant bone-level change between the two prosthetic groups, either at the prosthesis or at the implant level. CONCLUSION Data on implant-supported FPDPs with cantilever extensions are limited and therefore survival and complication rates should be interpreted with caution. The incorporation of cantilevers into implant-borne prostheses may be associated with a higher incidence of minor technical complications.
Occurrence and distribution pattern of acidic pharmaceuticals in surface water, wastewater, and sediment of the Msunduzi River, Kwazulu‐Natal, South Africa

The paucity of information on the occurrence of pharmaceuticals in the environment in African countries led the authors to investigate 8 acidic pharmaceuticals (4 antipyretics, 3 antibiotics, and 1 lipid regulator) in wastewater, surface water, and sediments from the Msunduzi River in the province of KwaZulu‐Natal, South Africa, using solid‐phase extraction (SPE) and liquid chromatography–mass spectrometry (LC/MS). The method recoveries, limits of detection (LOD), and limits of quantification were determined. The method recoveries were 58.4% to 103%, and the LODs ranged between 1.16 ng/L and 29.1 ng/L for water and between 0.58 ng/g and 14.5 ng/g for sediment. The drugs were all present in wastewater and in most of the surface water and sediment samples. Aspirin was the most abundant pharmaceutical observed, 118 ± 0.82 μg/L in wastewater influent, and the most observed antibiotic was nalidixic acid (25.2–29.9 μg/L in wastewater); bezafibrate was the least observed. The distribution pattern of the antipyretic in water indicates more impact in suburban sites. The solid–liquid partitioning of the pharmaceuticals between sediment and water, measured as the distribution coefficient (log KD) gave an average accumulation magnitude of 10× to 32× in sediments than in water. The downstream distribution patterns for both water and sediment indicate discharge contributions from wastewater, agricultural activities, domestic waste disposal, and possible sewer system leakages. Although concentrations of the pharmaceuticals were comparable with those obtained from some other countries, the contamination of the present study site with pharmaceuticals has been over time and continues at present, making effective management and control necessary. Environ Toxicol Chem 2016;35:36–46. © 2015 SETAC
Mesopic Pupil Size in a Refractive Surgery Population (13,959 Eyes)

Purpose. To evaluate factors that may affect mesopic pupil size in refractive surgery candidates. Methods. Medical records of 13,959 eyes of 13,959 refractive surgery candidates were reviewed, and one eye per subject was selected randomly for statistical analysis. Detailed ophthalmological examination data were obtained from medical records. Preoperative measurements included uncorrected distance visual acuity, corrected distance visual acuity, manifest and cycloplegic refraction, topography, slit lamp examination, and funduscopy. Mesopic pupil size measurements were performed with Colvard pupillometer. Relationship between mesopic pupil size and age, gender, refractive state, average keratometry, and pachymetry (thinnest point) were analyzed by means of ANOVA (+ANCOVA) and multivariate regression analyses. Results. Overall mesopic pupil size was 6.45 ± 0.82 mm, and mean age was 36.07 years. Mesopic pupil size was 5.96 ± 0.8 mm in hyperopic astigmatism, 6.36 ± 0.83 mm in high astigmatism, and 6.51 ± 0.8 mm in myopic astigmatism. The difference in mesopic pupil size between all refractive subgroups was statistically significant (p < 0.001). Age revealed the strongest correlation (r = −0.405, p < 0.001) with mesopic pupil size. Spherical equivalent showed a moderate correlation (r = −0.136), whereas keratometry (r = −0.064) and pachymetry (r = −0.057) had a weak correlation with mesopic pupil size. No statistically significant difference in mesopic pupil size was noted regarding gender and ocular side. The sum of all analyzed factors (age, refractive state, keratometry, and pachymetry) can only predict the expected pupil size in <20% (R2 = 0.179, p < 0.001). Conclusions. Our analysis confirmed that age and refractive state are determinative factors on mesopic pupil size. Average keratometry and minimal pachymetry exhibited a statistically significant, but clinically insignificant, impact on mesopic pupil size.
Optimal concession contracts for landlord port authorities under price competition of terminal operators

This paper extends Chen and Liu's (2014) study by assuming that terminal operators compete in prices, instead of in quantities. Under this setting, the paper shows that the two-part tariff contract is the port authority's best choice. In addition, the paper refines the outcomes of Chen and Liu (2014) by showing that the two-part tariff contract, rather than the unit-fee contract, is the optimal choice for the port authority if the marginal service costs of the less efficient operator are small. The results presented here and Chen and Liu (2014) imply that the two-part tariff contract is the best solution for landlord port authorities under different competing modes and cost structures of terminal operators, as well as under various service differentiation levels of the operators. The port authority and the more efficient operator may prefer price or quantity competition. Terminal operators' service differentiation levels and their marginal service costs will determine the results. However, the less efficient operator will always prefer quantity to price competition if it survives in the market.
Maternal lifetime history of depression and depressive symptoms in the prenatal and early postnatal period do not predict infant–mother attachment quality in a large, population-based Dutch cohort study

We examined the effects of maternal history of depressive disorder and the effects of depressive symptoms during pregnancy and the early postpartum period on attachment insecurity and disorganization. A total of 627 mother–infant dyads from the Generation R Study participated in a population-based cohort from fetal life onwards. Maternal history of depression was assessed by diagnostic interviews during pregnancy; maternal peri- and postnatal depressive symptoms were assessed with questionnaires in 506 of these women at 20 weeks pregnancy and two months postpartum; and infant–mother attachment security was observed when infants were aged 14 months. A history of maternal depressive disorder, regardless of severity or psychiatric comorbidity, was not associated with an increased risk of infant attachment insecurity or disorganization. Likewise, maternal peri- and postnatal depressive symptoms were not related to attachment insecurity or disorganization at 14 months. These results are important because mothers from otherwise low risk backgrounds often have previously been depressed or are struggling with non-clinical depressive symptoms during pregnancy and after giving birth. Our findings are discussed in terms of protective factors that may limit the potentially negative effects of maternal depressive symptoms on the infant–mother attachment relationship in the general population. The role of selective attrition and lack of information about the mothers' attachment status for the current null-findings are also discussed.
[Lys(B28), Pro(B29)]-Human Insulin: A Rapidly Absorbed Analogue of Human Insulin

[Lys(B28, Pro(B29)]-human insulin (LYSPRO) is an insulin analogue in which the natural amino acid sequence of the B-chain at positions 28 and 29 is inverted. These changes result in an insulin molecule with a greatly reduced capacity for self-association in solution. These clinical studies were designed to compare LYSPRO with human Regular insulin after subcutaneous injection in humans. We wanted to evaluate the effect of adding zinc to LYSPRO on its pharmacokinetics and pharmacodynamics. In addition, we compared the pharmacokinetics and pharmacodynamics of LYSPRO and human Regular insulin after subcutaneous injection to those of human Regular insulin given intravenously. Thus, we compared four treatments: solutions of zinc-free LYSPRO given subcutaneously (A), zinc-containing LYSPRO given subcutaneously (B), human Regular insulin given subcutaneously (C), and human Regular insulin given intravenously (D). We gave a 10-U dose of each treatment to 10 healthy (nondiabetic) men during glucose clamps. Serum insulin concentrations peaked more than two times higher (maximum serum insulin level [Cmax], 698 vs. 308 pM, A vs. C) and in < half the time (time to Cmax [Tmax], 42 vs. 101 min, A vs. C) after subcutaneous injection of zinc-free LYSPRO. At the same time, the glucose infusion rate peaked in about half the time (time to maximum glucose infusion rate [TRmax], 99 vs. 179 min, A vs. C) and was slightly but not significantly higher (maximum glucose infusion rate [Rmax], 3.1 vs. 2.2 mmol/min, A vs. C) than that of human Regular insulin. Although the addition of zinc retarded the absorption of LYSPRO slightly (Cmax, 550 vs. 698 pM, B vs. A), zinc-containing LYSPRO retained its distinct profile (Tmax 53 vs. 42 min, B vs. A). LYSPRO displays faster pharmacodynamic action than human Regular insulin when injected subcutaneously
The von Willebrand Factor A3 Domain Does Not Contain a Metal Ion-dependent Adhesion Site Motif*

von Willebrand factor (vWF) is a multimeric plasma protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury. The A3 domain of vWF (vWF-A3) forms the principal binding site for collagens type I and III. We report here the crystal structure of the vWF-A3 domain at 2.2-Å resolution. As expected, the structure is similar to the integrin I domain but with several novel features. Sequence alignments had suggested that the domain contained an integrin metal ion-dependent adhesion site (MIDAS) motif, but the crystal structure shows that the motif is modified and that no metal ion is bound. We have introduced mutations into the vestigial MIDAS motif and report that, unlike the I domain of integrin α2β1, vWF-A3 continues to bind collagen after disruption of the motif. We conclude that collagen recognition by vWF-A3 occurs by a mechanism different from that of the integrin α2β1.
Co-Morbidity of Infectious and Addictive Diseases in St. Petersburg and the Leningrad Region, Russia

The Russian health care system is organized around specific diseases, with relatively little focus on integration across specialties to address co-morbidities. This organizational structure presents new challenges in the context of the recent epidemics of injection drug use (IDU) and HIV. This paper uses existing and new data to examine the prevalence of reported new cases of drug dependence (heroin) and HIV over time as well as associations between drug dependence and alcoholism, hepatitis B and C, and tuberculosis in the City of St. Petersburg and the Leningrad region. We found a sharp rise in reported cases of IDU beginning in 1991 and continuing until 2002/2003, followed by a sharp rise in newly reported cases of HIV. These rises were followed by a drop in new cases of HIV and drug addiction in 2002/2003 and a drop in the proportion of HIV-positve individuals with IDU as a risk factor. Infection with hepatitis B and C were common, especially among injection drug users (38 and 85%, respectively), but also in alcoholics (7 and 14%). Tuberculosis was more common in alcoholics (53%) than in persons with alcoholism and drug dependence (10%), or with drug dependence alone (4%). Though these data have many limitations, they clearly demonstrate that drug dependence and/or alcoholism, HIV, hepatitis, and tuberculosis frequently co-occur in St. Petersburg and the Leningrad Region. Prevention and treatment services across medical specialties should be integrated to address the wide range of issues that are associated with these co-morbidities.
Distinct Neurophysiological Mechanisms Mediate Mixing Costs and Switch Costs

Using event-related potentials (ERPs), we investigated the neural response associated with preparing to switch from one task to another. We used a cued task-switching paradigm in which the interval between the cue and the imperative stimulus was varied. The difference between response time (RT) to trials on which the task switched and trials on which the task repeated (switch cost) decreased as the interval between cue and target (CTI) was increased, demonstrating that subjects used the CTI to prepare for the forthcoming task. However, the RT on repeated-task trials in blocks during which the task could switch (mixed-task blocks) were never as short as RTs during single-task blocks (mixing cost). This replicates previous research. The ERPs in response to the cue were compared across three conditions: single-task trials, switch trials, and repeat trials. ERP topographic differences were found between single-task trials and mixed-task (switch and repeat) trials at ∼160 and ∼310 msec after the cue, indicative of changes in the underlying neural generator configuration as a basis for the mixing cost. In contrast, there were no topographic differences evident between switch and repeat trials during the CTI. Rather, the response of statistically indistinguishable generator configurations was stronger at ∼310 msec on switch than on repeat trials. By separating differences in ERP topography from differences in response strength, these results suggest that a reappraisal of previous research is appropriate.
Kindling induces the long-lasting expression of a novel population of NMDA receptors in hippocampal region CA3

Kindling refers to a phenomenon in which repeated application of initially subconvulsive electrical stimulations produces limbic and clonic motor seizures of progressively increasing severity. Once established, the increased excitability is lifelong. Enhanced function of synapses using the NMDA subtype of glutamate receptor could contribute to the expression of the increased excitability. We previously found that CA3 pyramidal cells of hippocampus of kindled animals exhibit a selective and long-lasting (1 month) increased sensitivity to NMDA-evoked depolarization. The goal of this study was to develop a molecular explanation of the enhanced sensitivity to NMDA. We used radioligand binding studies of membranes isolated from microdissected regions of hippocampus including fascia dentata, CA3, and CA1. We also used quantitative in situ hybridization with subtype- specific riboprobes or oligonucleotides to determine whether increased expression of one or more of the genes encoding NMDA receptors was present in hippocampal granule and pyramidal cells of kindled animals. When studied 28 d after the last evoked seizure, we found that kindling induced a 2.8-fold increase in the number of binding sites for the competitive NMDA receptor antagonist 3-[(+/-)-2-(carboxypiperazine-4- yl)][1,2–3H-]propyl-1-phosphonic acid (3H-CPP). This increase was confined to region CA3 within the hippocampus. Similar, though much smaller, changes were detected 24 hr after the last evoked seizure. Surprisingly, no changes in the binding of another competitive NMDA receptor antagonist, cis-4-(phosphonomethyl)-2–3H-piperidinecarboxylate (3H-CGS-19755), were detected at either time point in any hippocampal region. Transcript levels of the NMDA receptor genes NMDAR1, NR2A, NR2B, NR2C, and NR2D and a glutamate-binding protein (GBP) were not altered by kindling. These findings demonstrate that kindling induces the expression of an NMDA receptor that is novel in that it is recognized by 3H-CPP but not by 3H-CGS-19755. The molecular basis of this novel NMDA receptor is not determined by differential expression of mRNA transcripts of known NMDA receptor genes. The direction, time course, and location of the kindling-induced increase in 3H-CPP binding suggest that this novel receptor may underlie the increased sensitivity of CA3 neurons to NMDA observed in kindled animals.
Depression Among Southern Rural African American Women: A Factor Analysis of the Beck Depression Inventory-II

Background:This is the first reported study involving a factor analysis of the Beck Depression Inventory-II, which was administered to a sample of southern rural African American women. Objective:To determine the factor structure of the Beck Depression Inventory-II using data collected from southern rural African American women. Methods:Using a correlational, descriptive design, 206 southern rural African American women were invited to participate in a face-to-face interview that occurred in a variety of community-based settings. Results:The factor analysis of the Beck Depression Inventory-II resulted in a two-factor solution. Symptoms such as pessimism and worthlessness loaded high on the first factor (cognitive). The second factor explained somatic-affective symptoms of depression, with factor loadings high on tiredness and fatigue and loss of energy. Conclusions:The application of the Beck Depression Inventory-II among African American people would generate needed information about how depressive symptoms may be expressed among them. Knowledge gained from this study promises to be useful for developing appropriate research studies and population-specific treatment approaches for this group of women.
Radiographic Results After Percutaneous Distal Metatarsal Osteotomy for Correction of Hallux Valgus Deformity

Background: The goal of the study was to evaluate the short-term radiographic results and complications of a percutaneous distal metatarsal osteotomy for hallux valgus. Methods: From June, 2005, until October, 2005, a percutaneous distal first metatarsal osteotomy was performed in 13 consecutive patients. All patients had mild to moderate hallux valgus deformities preoperatively. The mean postoperative followup was 130 (range 50 to 207) days. The radiographs were reviewed for hallux valgus angle, 1-2 intermetatarsal angle, nonunion, malunion, and osteonecrosis. Results: The mean 2 weeks postoperative hallux valgus angle demonstrated a statistically significant (p < 0.0001) improvement from 25 (16 to 33) degrees preoperatively to 5 (−1 to 12) degrees postoperatively. Nine patients (69%) demonstrated dorsally angulated alignment of the first metatarsal at the first postoperative examination averaging 10.8 (6 to 15) degrees that increased to 15.9 (10 to 22) degrees at final followup. One patient developed cystic changes within the metatarsal head consistent with osteonecrosis. One patient developed a nonunion with no evidence of radiographic healing at most recent followup of 180 days. Five patients (38%) had recurrent hallux valgus defined as a final angle of greater than 15 degrees. Conclusions: Percutaneous distal metatarsal osteotomy for hallux valgus is associated with an unacceptable rate of complications, specifically, osteonecrosis, nonunion, malunion, and recurrence. The intraoperative correction was routinely lost after removal of the intramedullary Kirschner wire, leading to a high rate of recurrence of hallux valgus deformity as well as dorsal elevation of the capital fragment.