Miracle-dz/UniFAR-FTUs huggingface dataset:
Importance of Contrast-Enhanced Fluid-Attenuated Inversion Recovery Magnetic Resonance Imaging in Various Intracranial Pathologic Conditions

Intracranial lesions may show contrast enhancement through various mechanisms that are closely associated with the disease process. The preferred magnetic resonance sequence in contrast imaging is T1-weighted imaging (T1WI) at most institutions. However, lesion enhancement is occasionally inconspicuous on T1WI. Although fluid-attenuated inversion recovery (FLAIR) sequences are commonly considered as T2-weighted imaging with dark cerebrospinal fluid, they also show mild T1-weighted contrast, which is responsible for the contrast enhancement. For several years, FLAIR imaging has been successfully incorporated as a routine sequence at our institution for contrast-enhanced (CE) brain imaging in detecting various intracranial diseases. In this pictorial essay, we describe and illustrate the diagnostic importance of CE-FLAIR imaging in various intracranial pathologic conditions.
The most common nonconformities encountered during the assessments of medical laboratories in Hong Kong using ISO 15189 as accreditation criteria

Introduction: ISO 15189 was a new standard published in 2003 for accrediting medical laboratories. We believe that some requirements of the ISO 15189 standard are especially difficult to meet for majority of laboratories. The aim of this article was to present the frequency of nonconformities to requirements of the ISO 15189 accreditation standard, encountered during the assessments of medical laboratories in Hong Kong, during 2004 to 2009. Materials and methods: Nonconformities reported in assessments based on ISO 15189 were analyzed in two periods – from 2004 to 2006 and in 2009. They are categorized according to the ISO 15189 clause numbers. The performance of 27 laboratories initially assessed between 2004 and 2006 was compared to their performance in the second reassessment in 2009. Results: For management requirements, nonconformities were most frequently reported against quality management system, quality and technical records and document control; whereas for technical requirements, they were reported against examination procedures, equipment, and assuring quality of examination procedures. There was no major difference in types of common nonconformities reported in the two study periods. The total number of nonconformities reported in the second reassessment of 27 laboratories in 2009 was almost halved compared to their initial assessments. The number of significant nonconformities per laboratory significantly decreased (P = 0.023). Conclusion: Similar nonconformities were reported in the two study periods though the frequency encountered decreased. The significant decrease in number of significant nonconformities encountered in the same group of laboratories in the two periods substantiated that ISO15189 contributed to quality improvement of accredited laboratories.
International Scoring System in Symptomatic Multiple Myeloma: Experience from a Tertiary Care Center.

BACKGROUND Symptomatic multiple myeloma (MM) is an acquired B-cell malignant proliferation of anti- body secreting plasma cells, characterized by end organ damage due to monoclonal immunoglobulin secretion. The aim of this study wa to determine the stage stratification according to an international scoring system in adult Pakistani MM patients at presentation. MATERIALS AND METHODS This single centre retrospective study extendedfrom January 2012 to December 2015. Data were retrieved from the departmental maintained records. RESULTS A total of 39 patients were diagnosed at our center with MM during the period of the study, 25 males and 14 females. Age ranged between 36 and 81 with a mean of 54.5±14.8 and a median of 57 years. Common presenting complaints included fatigue (80.9%), backache (79.3%) and bone pain (66.2%). Overall, 9 patients were in ISS stage I (23%), 12 were in stage II (30.7%) and 18 were in stage III (46.1%). Out of the total, 29 (74.3%) had kappa immunoglobulin andthe remaining 10 (25.6%) had lambda type myelomas. IgG myeloma was commonest, seen in 26 (66.6%) followed by IgA in 11 (28.2%) with non secretory myeloma in one (2.5%) and light chain disease also in one patient (2.5%). CONCLUSIONS MM in Pakistani patients is seen in a relatively young population with male predominance. Primarily patients are symptomatic and risk stratification revealed a predominance of advanced stage III disease in our setting.
The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice

SUMMARY Ascariasis is an important infection in humans (Ascaris lumbricoides) and pigs (Ascaris suum) and individuals appear to be predisposed to either heavy or light worm burdens. These extremes of susceptibility and resistance are represented in a mouse model by 2 strains of mice, CBA mice showing high resistance to infection and C57BL/6 which are highly susceptible, as reflected in worm burdens in the lungs 6–7 days after infection. In an attempt to identify the point at which the difference between these 2 strains is first manifested, we quantified worm burdens at key stages during infection leading up to the pulmonary stage of development. Thus mice were inoculated with fully embryonated A. suum eggs and larval burdens were enumerated in the large intestine and rectum, liver and lungs of the 2 strains at 6 h post-inoculation (p.i.) and on each of days 1–8 p.i. inclusively. A higher percentage of the total inoculum was recovered from the intestine/rectum of C57BL/6j mice in contrast to CBA/Ca mice at 6 h p.i. Larvae were recovered from the intestinal contents and also whilst actively migrating through the large intestinal wall. The number of larvae recovered was significantly reduced in CBA/Ca mice in contrast to C57BL/6j mice between the phase of migration from the liver and arrival in the lungs. The combined results of the inoculation of mice with corticosteroids and the examination of the change in profile and number of leukocytes present in bronchoalveolar lavage fluid suggested that the pulmonary inflammatory immune response was not prominently involved in primary protection of mice to A. suum infection in the latter days of infection in the lungs. The susceptible C57BL/6j mice produced a BAL response almost twice as intense as that of resistant CBA/Ca mice with stronger neutrophil, lymphocyte and eosinophil but not macrophage components, suggesting that the difference in worm burdens between the strains was generated earlier in the course of infection. These results were further corroborated by a histological examination of the lung tissues which showed that the passage of the larval stages of A. suum through the mouse lungs was associated with a marked inflammatory response in both strains. Again, C57BL/6j mice exhibited increased inflammation relative to CBA/Ca mice. Hence some hepatic/post-hepatic factor that varies between the 2 strains, but exerts its effect before the lung phase plays a critical role in determining the success of larvae through the host tissues. The possible sites of this host defence are reviewed.
Modified Transtibial versus Anteromedial Portal Technique in Single Bundle ACL Reconstruction

Objectives: The aim of this study is to determine whether it is possible to achieves a similar anatomical placement of the femoral tunnel with a modified transtibial ACL single bundle reconstruction tecnique compared to anteromedial transportal technique. Results were evaluated by tomographic comparisons between patients from both groups. Methods: 36 patients (36 knees) who were candidates for an ACL single bundle reconstruction with patellar bone graft were included in the study. Patients were randomly allocated using a computerized sequence into two groups. 18 patients were assigned each group (modified transtibial vs AM transportal technique). Surgery was performed by the same surgical team in both groups. Femoral tunnel quadrant placement, oblicuity in the coronal and sagittal planes and diameter of the femoral tunnel were assesed tomographically blinded by two observers and statistical comparison between groups was realized. Results: Average distance measured from posterior edge of the condyle to the femoral tunnel ( measured as a proportion respect to the T line) was similar in both groups ( Group I : 32.7 % +- 5.1% ; Group 2: 32.4 % +-4.4% , p = 0.85). Average distance measured from the Blumensaat line to the femoral tunnel (measured as a proportion respect to the H line) was similar in both groups ( Group I: 28.5% 4.49 % Group II , 31.5% of 4.83% p = 0.06). Average angulation values of the femoral tunnel in the coronal plane were lower in Group I than in Group II (Group I = 34.8 ° range 32.7 ° - 38.6 ° and 41.2 ° range Group II 36.7 ° - 43.1 ° P = 0.0016 ). Average angulation values of the femoral tunnel in the sagittal plane were similar in both groups (Group I 40.2 ° range 38.4 ° - 43.4 ° ; Group II 38 1 ° range 36.6 ° - 40.2 ° p = 0.17). The average diameter of the femoral tunnel was significantly higher in group I than in Group II (Group I 11 mm 0.84 mm and 10.2 mm Group II 0.65mm p = 0.007) . Conclusion: The modified transtibial technique for single bundle ACL reconstruction has proved to be suitable to reproduce the anatomic placement of the femoral tunnel compared to the transportal AM technique.
Rec2 Interplay with both Brh2 and Rad51 Balances Recombinational Repair in Ustilago maydis

ABSTRACT Rec2 is the single Rad51 paralog in Ustilago maydis. Here, we find that Rec2 is required for radiation-induced Rad51 nuclear focus formation but that Rec2 foci form independently of Rad51 and Brh2. Brh2 foci also form in the absence of Rad51 and Rec2. By coprecipitation from cleared extracts prepared from Escherichia coli cells expressing the proteins, we found that Rec2 interacts physically not only with Rad51 and itself but also with Brh2. Transgenic expression of Brh2 in rec2 mutants can effectively restore radiation resistance, but the frequencies of spontaneous Rad51 focus formation and allelic recombination are elevated. The Dss1-independent Brh2-RPA70 fusion protein is also active in restoring radiation sensitivity of rec2 but is hyperactive to an extreme degree in allelic recombination and in suppressing the meiotic block of rec2. However, the high frequency of chromosome missegregation in meiotic products is an indicator of a corrupted process. The results demonstrate that the importance of Rec2 function is not only in stimulating recombination activity but also in ensuring that recombination is properly controlled.
A Novel Panel of Cerebrospinal Fluid Biomarkers for the Differential Diagnosis of Alzheimer’s Disease versus Normal Aging and Frontotemporal Dementia

Background: An early and accurate diagnosis of Alzheimer’s disease (AD) is important in order to initiate symptomatic treatment with currently approved drugs and will be of even greater importance with the advent of disease-modifying compounds. Methods: Protein profiles of human cerebrospinal fluid samples from patients with AD (n = 85), frontotemporal dementia (n = 20), and healthy controls (n = 32) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to verify previously discovered biomarkers. Results: We verified 15 protein biomarkers that were able to differentiate between AD and controls, and 7 of these 15 markers also differentiated AD from FTD. Conclusion: A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.
School-based counseling using systematic feedback: A cohort study evaluating outcomes and predictors of change

Abstract The outcomes of school-based counseling incorporating the Partners for Change Outcome Monitoring System (PCOMS) were evaluated using a cohort design, with multilevel modeling to identify predictors of change. Participants were 288 7–11 year olds experiencing social, emotional or behavioral difficulties. The intervention was associated with significant reductions in psychological distress, with a pre-post effect size (d) of 1.49 on the primary outcome measure and 88.7% clinical improvement. Greater improvements were found for disabled children, older children, and where CBT methods were used. The findings provide support for the use of systematic feedback in therapy with children.
Reexcision and perioperative high-dose-rate brachytherapy in the treatment of local relapse after breast conservation: an alternative to salvage mastectomy

Purpose To evaluate the feasibility and efficacy of second breast-conserving surgery with reirradiation using perioperative high-dose-rate interstitial brachytherapy for the treatment of local recurrence developing after previous breast-conserving therapy. Material and methods Between 1999 and 2007, twelve patients with isolated local recurrence initially treated for breast carcinoma with the use of conservative surgery and radiation therapy, underwent a repeat breast-conserving surgery and perioperative high-dose-rate multicatheter brachytherapy. Breast cancer related events, late side effects, and cosmetic results were assessed retrospectively. Results At a median follow-up of 56 months (range: 8-112) second local recurrence has not occurred, yielding a 100% mastectomy-free survival. Four patients (33.3%) developed subsequent distant metastasis and died of breast cancer. The 5-year actuarial rate of disease-free, cancer-specific, and overall survival was 65.6%, 78.6%, and 78.6%, respectively. Cosmetic results were rated good, fair, poor and unknown in 6 (50%), 2 (17%), 1 (8%) and 3 (25%) patients, respectively. Grade 2 skin toxicity and fibrosis occurred in 1 (8%) and 2 (17%) patients. Asymptomatic fat necrosis was detected in 6 (50%) women. No patient developed grade 3-4 late side effects. Conclusions Second breast-conserving surgery followed by partial breast reirradiation is a safe and effective option for the management of selected patients developing local recurrence after previous breast-conserving therapy. Perioperative high-dose-rate brachytherapy with adequate fractionation may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects.
Three-dimensional Finite Element Analysis of Endodontically Treated Tooth Restored with Carbon and Titanium Posts

Aim: This study compared the stress distributions of endodontically treated tooth restored with carbon and titanium post during different loading conditions. Methodology: A 3-dimensional finite element model was created to represent an endodontically treated maxillary central incisor tooth with its supporting structures. Stress distribution and stress values were then calculated by considering the three dimensional von Mises stress criteria. Results: A 100-N static vertical occlusal load was applied on the node at the center of occlusal surface of the tooth. The von Mises stress values for carbon post model was on the coronal third and the cervical area of the root in the range of 353.149 and 13.878 MPa, for titanium post model was 540.736 and 22.777 MPa. Conclusion: This study shows that the titanium post yields larger stresses than the carbon post. How to cite this article: Adiguzel O, Kaya S, Yigit Ozer S, Deger Y, Goncu Basaran E, Yavuz I. Three-dimensional Finite Element Analysis of Endodontically Treated Tooth Restored with Carbon and Titanium Posts. Int Dent Res 2011;2:55-59. Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.
Effect of CaF2 and Li2O Additives on the Viscosity of CaO–SiO2–Na2O Slags

High aluminum containing steels react vigorously with silica-based mold fluxes to form alumina. The change in alumina content increases the viscosity and thus silica-based mold fluxes are compensated with significant amounts of Na2O, CaF2, and Li2O to ensure both lubrication and heat transfer control. Detailed viscosity studies using the rotating spindle method showed that additions of CaF2 up to 8 wt% in the CaO–SiO2–12wt%Na2O system at a constant CaO/SiO2 ratio of 0.8 decreases the viscosity by breaking the network structure of molten fluxes, but is negligible above 8 wt%. A similar modification of the network was observed for Li2O up to 2 wt%. The viscosity data was correlated with the XPS analysis and verified CaF2 and Li2O as effective in modifying complex silicate structures into simpler silicate structures depending on the availability of complex silicates and thus was limited to below certain concentrations.
A Novel T55A Variant of Gs α Associated with Impaired cAMP Production, Bone Fragility, and Osteolysis

G-protein coupled receptors (GPCRs) mediate a wide spectrum of biological activities. The GNAS complex locus encodes the stimulatory alpha subunit of the guanine nucleotide binding protein (Gsα) and regulates production of the second messenger cyclic AMP (cAMP). Loss-of-function GNAS mutations classically lead to Albright's Hereditary Osteodystrophy (AHO) and pseudohypoparathyroidism, often with significant effects on bone formation and mineral metabolism. We present the case of a child who exhibits clinical features of osteolysis, multiple childhood fractures, and neonatal SIADH. Exome sequencing revealed a novel de novo heterozygous missense mutation of GNAS (c.163A<G, p.T55A) affecting the p-loop of the catalytic Gsα GTPase domain. In order to further assess whether this unique mutation resulted in a gain or loss of function of Gsα, we introduced the mutation into a rat GNAS plasmid and performed functional studies to assess the level of cAMP activity associated with this mutation. We identified a 64% decrease in isoproterenol-induced cAMP production in vitro, compared to wild type, consistent with loss of Gsα activity. Despite a significant decrease in isoproterenol-induced cAMP production in vitro, this mutation did not produce a classical AHO phenotype in our patient; however, it may account for her presentation with childhood fractures and osteolysis.
Hypochlorous acid‐induced heme oxygenase‐1 gene expression promotes human endothelial cell survival

Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell (EC) dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase‐1 (HO‐1) in and around ECs of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human ECs with the myeloperoxidase product HOCl stimulated a concentration‐ and time‐dependent increase in HO‐1 mRNA, protein, and promoter activity, and carbon monoxide synthesis that was preceded by a marked rise in Nrf2 protein. The HOCl‐mediated increase in HO‐1 promoter activity was blocked by mutating the antioxidant response element in the promoter or by overexpressing a dominant‐negative mutant of Nrf2. The induction of Nrf2 or HO‐1 by HOCl was prevented by N‐acetyl‐L‐cysteine. Finally, treatment of ECs with HOCl stimulated cell death that was potentiated by the HO inhibitor tin protoporphyrin‐IX or by the selective knockdown of HO‐1. These results demonstrate that HOCl induces HO‐1 gene transcription via the redox‐dependent activation of Nrf2 to counteract HOCl‐mediated toxicity. The ability of HOCl to activate Nrf2 and stimulate HO‐1 gene expression may represent a critical adaptive response to maintain EC viability at sites of vascular inflammation and atherosclerosis. Supported by NIH and AHA.
African apes as reservoirs of Plasmodium falciparum and the origin and diversification of the Laverania subgenus

We investigated two mitochondrial genes (cytb and cox1), one plastid gene (tufA), and one nuclear gene (ldh) in blood samples from 12 chimpanzees and two gorillas from Cameroon and one lemur from Madagascar. One gorilla sample is related to Plasmodium falciparum, thus confirming the recently reported presence in gorillas of this parasite. The second gorilla sample is more similar to the recently defined Plasmodium gaboni than to the P. falciparum–Plasmodium reichenowi clade, but distinct from both. Two chimpanzee samples are P. falciparum. A third sample is P. reichenowi and two others are P. gaboni. The other chimpanzee samples are different from those in the ape clade: two are Plasmodium ovale, and one is Plasmodium malariae. That is, we have found three human Plasmodium parasites in chimpanzees. Four chimpanzee samples were mixed: one species was P. reichenowi; the other species was P. gaboni in three samples and P. ovale in the fourth sample. The lemur sample, provisionally named Plasmodium malagasi, is a sister lineage to the large cluster of primate parasites that does not include P. falciparum or ape parasites, suggesting that the falciparum + ape parasite cluster (Laverania clade) may have evolved from a parasite present in hosts not ancestral to the primates. If malignant malaria were eradicated from human populations, chimpanzees, in addition to gorillas, might serve as a reservoir for P. falciparum.
Use of Reference Frame and Movement Pattern in Haptically Enhanced 3D Virtual Environment

For the present article a haptically enhanced 3D virtual environment was created, and this study investigates how visually impaired users perceive and explain the virtual space when haptic is the only input modality. The study investigates what factors affect the use of reference frame when the users verbally express a haptically constructed mental map and how such preference corresponds to their haptic movement in the virtual environment. In the study, gravity was the most influential cue in determining a vertical axis of a frame. When the users were asked to explain the relationship between themselves and the target object, they had the tendency to use the frame they initially chose to use. It was also noted that totally blind users were more responsive to various frames than users with lower vision and were faster in determining a term to explain spatial relationship. Furthermore, people who preferred relative frame were more likely to keep the haptic cursor closer to their body. Limited range of exploration caused lack of understanding of the space, whereas longer exploration time made them use more frames.
QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance

Abstract Of late, solid self-nanoemulsifying drug delivery systems (S-SNEDDS) have been extensively sought-after owing to their superior portability, drug loading, stability and patient compliance. The current studies, therefore, entail systematic development, optimization and evaluation (in vitro, in situ and in vivo) of the solid formulations of (SNEDDS) lovastatin employing rational quality by design (QbD)-based approach of formulation by design (FbD). The patient-centric quality target product profile (QTPP) and critical quality attributes (CQAs) were earmarked. Preformulation studies along with initial risk assessment facilitated the selection of lipid (i.e. Capmul MCM), surfactant (i.e. Nikkol HCO-50) and co-surfactant (i.e. Lutrol F127) as CMAs for formulation of S-SNEDDS. A face-centered cubic design (FCCD) was employed for optimization using Nikkol-HCO50 (X1) and Lutrol-F127 (X2), evaluating CQAs like globule size, liquefaction time, emulsification time, MDT, dissolution efficiency and permeation parameter. The design space was generated using apt mathematical models, and the optimum formulation was located, followed by validation of the FbD methodology. In situ SPIP and in vivo pharmacodynamic studies on the optimized formulation carried out in unisex Wistar rats, corroborated superior drug absorption and enhanced pharmacodynamic potential in regulating serum lipid levels. In a nutshell, the present studies report successful QbD-oriented development of novel oral S-SNEDDS of lovastatin with distinctly improved biopharmaceutical performance.