Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal Stem Cells Can Be Differentiated Into Endothelial Cells In Vitro

Human bone marrow‐derived mesenchymal stem cells (MSCs) have the potential to differentiate into mesenchymal tissues like osteocytes, chondrocytes, and adipocytes in vivo and in vitro. The aim of this study was to investigate the in vitro differentiation of MSCs into cells of the endothelial lineage. MSCs were generated out of mononuclear bone marrow cells from healthy donors separated by density gradient centrifugation. Cells were characterized by flow cytometry using a panel of monoclonal antibodies and were tested for their potential to differentiate along different mesenchymal lineages. Isolated MSCs were positive for the markers CD105, CD73, CD166, CD90, and CD44 and negative for typical hematopoietic and endothelial markers. They were able to differentiate into adipocytes and osteocytes after cultivation in respective media. Differentiation into endothelial‐like cells was induced by cultivation of confluent cells in the presence of 2% fetal calf serum and 50 ng/ml vascular endothelial growth factor. Laser scanning cytometry analysis of the confluent cells in situ showed a strong increase of expression of endothelial‐specific markers like KDR and FLT‐1, and immunofluorescence analysis showed typical expression of the von Willebrand factor. The functional behavior of the differentiated cells was tested with an in vitro angiogenesis test kit where cells formed characteristic capillary‐like structures. We could show the differentiation of expanded adult human MSCs into cells with phenotypic and functional features of endothelial cells. These predifferentiated cells provide new options for engineering of artificial tissues based on autologous MSCs and vascularized engineered tissues.
The Common Vaccine Adjuvant Aluminum Hydroxide Up-Regulates Accessory Properties of Human Monocytes via an Interleukin-4-Dependent Mechanism

ABSTRACT Aluminum adjuvants are widely used in human vaccines based on their ability to enhance antibody production. However, the mechanisms underlying these effects remain unknown. In the present study we assessed the direct in vitro effect of aluminum hydroxide on human peripheral blood monocytes, specifically with regard to its impact on the phenotype and functional properties of this cell population. Our results revealed significant changes in the accessory properties of monocytes following short-term exposure of cultured cells to aluminum hydroxide. Thus, flow cytometry analyses showed an increase in the expression of major histocompatibility complex (MHC) class II, CD40, CD54, CD58, CD83, and CD86 molecules on the monocytes. In addition, many cells in the cultures containing aluminum hydroxide acquired typical dendritic morphology. Increased synthesis of interleukin-4 (IL-4) mRNA, but not gamma interferon mRNA, was also noted after exposure to aluminum hydroxide. The increase in cell surface expression of MHC class II did not occur in the presence of neutralizing IL-4 antibody or in cultures of highly purified monocytes or CD4-depleted mononuclear cells. Our findings suggest that aluminum hydroxide directly stimulates monocytes to produce proinflammatory cytokines activating T cells. Activated Th2 cells release IL-4, which in turn can induce an increase in the expression of MHC class II molecules on monocytes. The increase in the expression of antigen-presenting and costimulatory molecules leads to enhanced accessory functions of monocytes. These properties of aluminum hydroxide observed in vitro may explain its potent in vivo adjuvant effect.
Analysis of the MIRIAD Data Shows Sex Differences in Hippocampal Atrophy Progression.

BACKGROUND Hippocampus (HC) atrophy is a hallmark of early Alzheimer's disease (AD). Atrophy rates can be measured by high-resolution structural MRI. Longitudinal studies have previously shown sex differences in the progression of functional and cognitive deficits and rates of brain atrophy in early AD dementia. It is important to corroborate these findings on independent datasets. OBJECTIVE To study temporal rates of HC atrophy over a one-year period in probable AD patients and cognitively normal (CN) subjects by longitudinal MRI scans obtained from the Minimal Interval Resonance Imaging in AD (MIRIAD) database. METHODS We used a novel algorithm to compute an index of hippocampal (volumetric) integrity (HI) at baseline and one-year follow-up in 43 mild-moderate probable AD patients and 22 CN subjects in MIRIAD. The diagnostic power of longitudinal HI measurement was assessed using a support vector machines (SVM) classifier. RESULTS The HI was significantly reduced in the AD group (p < 10(-20)). In addition, the annualized percentage rate of reduction in HI was significantly greater in the AD group (p < 10(-13)). Within the AD group, the annual reduction of HI in women was significantly greater than in men (p = 0.008). The accuracy of SVM classification between AD and CN subjects was estimated to be 97% by 10-fold cross-validation. CONCLUSION In the MIRIAD patients with probable AD, the HC atrophies at a significantly faster rate in women as compared to men. Female sex is a risk factor for faster descent into AD. The HI measure has potential for AD diagnosis, as a biomarker of AD progression and a therapeutic target in clinical trials.
Effects of gestational age and prenatal and perinatal events on the coagulation status in premature infants

Objective: To study prospectively the effects of prematurity and perinatal events on the coagulation status of premature infants. Patients and main outcome measures: Blood samples from premature infants born before 37 gestational weeks were taken for analysis of coagulation factors II, V, VII, and X and platelet count. Results: A total of 125 premature infants, 71 boys, were studied at the median postnatal age of 40 minutes (range 12–100). The lowest median activities of coagulation factors II, V, VII, and X and the platelet count were observed, as expected, in infants (n = 21) born at 24–27 weeks gestation. Twin B (n = 14) had lower median activities of coagulation factors II, V, VII, and X than twin A. Infants with evidence of mild asphyxia (Apgar score at 5 minutes < 7 or cord pH < 7.26) had significantly (p < 0.05) lower levels of coagulation factors II, V, VII, and X and platelet counts than infants without asphyxia. Infants who were small for gestational age (SGA) had significantly (p < 0.05) lower levels of coagulation factors V and VII and platelet counts than infants of appropriate size for gestational age. Other prenatal and perinatal variables examined (sex, maternal hypertension and/or pre-eclampsia, antenatal steroid use, mode of delivery, Apgar scores) did not show any significant associations with coagulation status, which may be explained by the small number of infants studied. Conclusions: The data strongly suggest that there are distinct differences in specific coagulation tests in different patient populations, which could assist in the identification of extremely preterm, SGA, or asphyxiated preterm infants who may be susceptible to haemorrhagic problems perinatally.
Aspirin attenuates the incidence of silent brain lesions in patients with nonvalvular atrial fibrillation.

BACKGROUND Abnormal findings, including silent cerebral infarction, are frequently observed by magnetic resonance imaging (MRI) in patients with nonvalvular atrial fibrillation (NVAF); however, the prevalence and prevention strategy for these lesions have not been extensively studied. In the present study the preventive effects of aspirin on silent ischemic lesions was investigated. METHODS AND RESULTS Silent lesions were counted using cranial MRI performed in 78 neurologically normal adults with sinus rhythm and in 212 patients with NVAF without a history of stroke. MRIs were repeated twice in the NVAF patients at 12-month intervals. During the first year, patients received neither antiplatelet agent nor anticoagulant; in the second year, aspirin (330 mg daily) was administered. The prevalence of lesions in the initial MRI was higher in NVAF patients (86.4%) than in sinus rhythm subjects (53.8%; p<0.001). After 12 months without aspirin, new lesions were seen in 20.6% of NVAF patients. The yearly occurrence of new lesions was decreased to 9.6% during the year of treatment with aspirin (p=0.014). CONCLUSIONS In patients with NVAF, abnormal lesions are frequently observed by MRI and aspirin treatment may be effective in preventing further small silent lesions.
Mouthguard retention: is design or accuracy of fit more critical?

AIM To examine the influence of the accuracy of fit on mouthguard retention in relation to mouthguard outline location. MATERIALS AND METHODS Mouthguards were fabricated on a fully dentate maxillary cast with 4-mm thick ethylene vinyl acetate sheets using a well-dried cast (VD) and on a wet cast (VW) with a vacuum-forming machine. Mouthguards were also made with a pressure-forming machine (P). The mouthguard outline was set at 4 mm from the cervical margin (control, C), the palatal outline was set at the cervical margin (Pa), and the buccal outline was extended to the buccal fold (Bu). A dislodging force perpendicular to the occlusal plane was applied at the first molar on the universal testing machine. Results were analyzed using ANOVA with Scheffe's test (P < .05). RESULTS Using the VW, the retentive forces were statistically smaller at Pa compared to Ca or Bu (C: 58 +/- 17 gf, Pa: 36 +/- 7 gf , Bu: 50+/-8 gf) (P < .05). There were no statistical differences between VD (C: 116+/-27 gf, Pa: 86+/-15 gf, Bu: 92+/-7 gf) and group P (C: 133+/-31 gf, Pa: 139+/-24 gf, Bu: 136+/-17 gf). CONCLUSIONS The results indicate that mouthguard retention is closely related to the accuracy of fit at the cervical undercut area rather than the outline location.
Cerebral venous thrombosis during diabetic ketoacidosis

Neurological deterioration during an episode of diabetic ketoacidosis is usually assumed to be caused by cerebral oedema. We present a case of cerebral venous sinus thrombosis presenting in a similar manner, also associated with severe iron deficiency anaemia. Computed tomography scanning provided the correct diagnosis and allowed institution of anticoagulation with improvement in neurological outcome. Neuroimaging should always be performed in suspected cerebral oedema associated with diabetic ketoacidosis in order to exclude other pathologies.
Accumulated allelic losses in the development of invasive urothelial cancer

To investigate the roles of allelic loss in the development of urothelial cancer, loss of heterozygosity was examined on 7 chromosomal arms in 49 cases of urothelial cancer of various grades and stages. Loss of heterozygosity was found on alleles in order of frequency as follows: 9q (21/38, 55%), 11p (20/44, 45%), 17p (18/42,43%), 13q (10/39,26%), 3p (8/41, 20%), 10q 2/29, 7%) and 1p (1/36, 3%). lnvasive (high‐grade or ≥pT2) tumors showed the loss of 17p (13/16,81%) and the loss of 13q (7/16, 44%) with significantly higher frequencies than non‐invasive (grade 1‐2 ≤pTI ) tumors. Although the loss of 3p and the loss of 11p were also more frequently associated with the invasive phenotypes, the loss of 11p was detected in a considerable number (9 of 26,35%) of non‐invasive tumors. Our results indicate that the loss of 11p might generally occur at an earlier stage before the loss of 3p, 13q or 17p in tumor progression. Since no correlation was found between the loss of 9q and the tumor grade or stage, this genetic alteration appears to be unrelated to invasiveness, and could be one of the initial events in tumorigenesis. Although accumulated allelic losses of 3p, 11p, 13q and 17p are considered to be involved in the development of the invasive type of urothelial cancers, these multiple genetic alterations may have already occurred in some pathologically non‐invasive urothelial cancers. Furthermore, there appears to be some variation in the pattern of cumulative allelic loss.
QUANTITATIVE EVALUATION OF A HOME EXERCISE PROGRAM ON MUSCLE AND FUNCTIONAL CAPACITY OF PATIENTS WITH OSTEOARTHRITIS

ABSTRACT Rehabilitation of patients with osteoarthritis of the knees is typically based on home exercise. These programs are believed to benefit patients and have been shown to qualitatively improve strength. The purpose of the present study was to quantify the effects of a 3-mo home exercise program on muscle function and functional capacity. The progressive program included flexibility, strength, endurance, active range of motion and functional activities. Nineteen subjects (67.4 ± 7.5 yr) with osteoarthritis of the knees began the program, with only nine completing it. The subjects initially had significantly reduced muscle function and functional capacity. Maximal isometric strength of knee extension increased significantly at a knee flexion position of 45° for hip flexion positions of 120° and 60° (35%); however, it failed to increase at longer muscle lengths. There were no significant improvements in hamstring strength. Maximal angular velocity improved after 3 mo of exercise (40%). Muscle endurance did not improve significantly. Although there was a slight increase in functional capacity, these data failed to demonstrate significant clinical or statistical improvement in overall function in patients after home exercise.
Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis

Allergic rhinitis (AR) consists of three developmental stages that are based on the presence/absence of antigen‐specific IgE and symptoms. The pathogenic Th2 (Tpath2) cells constitute a population of Th2 cells with additional potentially pathogenic characteristics. We examined the relationship between Tpath2 cells and the stages of allergic rhinitis by focusing on ST2, which is an IL‐33 receptor.
Human flexor tendon tissue engineering: decellularization of human flexor tendons reduces immunogenicity in vivo.

BACKGROUND In mutilating hand injuries, tissue engineered tendon grafts may provide a reconstructive solution. We have previously described a method to decellularize cadaveric human flexor tendons while preserving mechanical properties and biocompatibility. The purpose of this study is to evaluate the immunogenicity and strength of these grafts when implanted into an immunocompetent rat model. METHODS Cadaveric human flexor tendons were divided into two groups. Group 1 was untreated, and Group 2 was decellularized by treatment with sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), and peracetic acid (PAA). Both groups were then analyzed for the presence of major histocompatibility complexes by immunohistochemistry (IHC). Pair-matched tendons from each group were then placed into the dorsal subcutaneous tissue and anchored to the spinal ligaments of Wistar rats for 2 or 4 weeks, and harvested. The infiltration of B-cells and macrophages was determined using IHC. The explants where then subjected to mechanical testing to determine the ultimate tensile stress (UTS) and elastic modulus (EM). Statistical analysis was performed using a paired Student's t-test. RESULTS The decellularization protocol successfully removed cells and MHC-1 complexes. At 2 weeks after implantation, there was increased infiltration of B-cells in Group 1 (untreated) compared with Group 2 (acellular), both in the capsule and tendon substance. There was improved ultimate tensile stress (UTS, 42.7 ± 8.3 vs. 22.8 ± 7.8 MPa, p<0.05) and EM (830.2 ± 206.7 vs. 421.2 ± 171.3 MPa, p<0.05) in tendons that were decellularized. At 4 weeks, there was continued B-cell infiltration in Group 1 (untreated) compared with Group 2 (acellular). There was no appreciable difference in macrophage infiltration at both time points. At 4 weeks Group 2 (acellular) demonstrated persistently greater UTS (40.5 ± 9.1 vs. 14.6 ± 4.2 MPa, p<0.05) and EM (454.05 ± 101.5 vs. 204.6 ± 91.3 MPa, p<0.05) compared with Group 1 (untreated). CONCLUSIONS Human flexor tendons that were decellularized with SDS, EDTA, and PAA resulted in removal of cellular antigens and a decreased immune response when placed into Wistar rats. These grafts showed better mechanical properties at 2 and 4 weeks when compared with control tendons. Decellularization is an important step toward the use of tissue engineered flexor tendons in upper extremity reconstruction.
A New Class of Repression Modules Is Critical for Heme Regulation of the Yeast Transcriptional Activator Hap1

ABSTRACT Heme plays key regulatory roles in numerous molecular and cellular processes for systems that sense or use oxygen. In the yeastSaccharomyces cerevisiae, oxygen sensing and heme signaling are mediated by heme activator protein 1 (Hap1). Hap1 contains seven heme-responsive motifs (HRMs): six are clustered in the heme domain, and a seventh is near the activation domain. To determine the functional role of HRMs and to define which parts of Hap1 mediate heme regulation, we carried out a systematic analysis of Hap1 mutants with various regions deleted or mutated. Strikingly, the data show that HRM1 to -6, located in the previously designated Hap1 heme domain, have little impact on heme regulation. All seven HRMs are dispensable for Hap1 repression in the absence of heme, but HRM7 is required for Hap1 activation by heme. More importantly, we show that a novel class of repression modules—RPM1, encompassing residues 245 to 278; RPM2, encompassing residues 1061 to 1185; and RPM3, encompassing residues 203 to 244—is critical for Hap1 repression in the absence of heme. Biochemical analysis indicates that RPMs mediate Hap1 repression, at least partly, by the formation of a previously identified higher-order complex termed the high-molecular-weight complex (HMC), while HRMs mediate heme activation by permitting heme binding and the disassembly of the HMC. These findings provide significant new insights into the molecular interactions critical for Hap1 repression in the absence of heme and Hap1 activation by heme.
Effects of branched-chain amino acids on placental amino acid transfer and insulin and glucagon release in the ovine fetus.

OBJECTIVE Competition for placental amino acid transporters can affect the fetal supply of amino acids. Specifically, the branched-chain amino acids-isoleucine, leucine, and valine-may inhibit the transfer of other amino acids. This study was undertaken to determine the effect of branched-chain amino acids on the umbilical uptake of amino acids. STUDY DESIGN Six late-gestation ewes were infused sequentially for 2 hours with 3 different mixtures of amino acids: (1) one that was comparable to commercial parenteral nutrition preparations, (2) the same solution without branched-chain amino acids, and (3) branched-chain amino acids alone. Maternal and fetal blood samples were collected simultaneously for the determination of uterine and umbilical uptake values of amino acids, and for concentrations of arterial insulin, glucagon, glucose, and lactate before (control) and during (experimental) infusion. RESULTS Umbilical uptake of branched-chain amino acids increased significantly when they were present in the infusates. The fetal uptake of several other amino acids could be increased by increasing their maternal concentrations. Inhibition of umbilical uptake by branched-chain amino acids could be shown for threonine and methionine. The infusion of branched-chain amino acids alone did not affect maternal and fetal insulin or glucagon concentrations. CONCLUSIONS In late-gestation sheep, an increase in maternal plasma concentration of branched-chain amino acids led to increased branched-chain amino acid umbilical uptake, but branched-chain amino acids can also inhibit the transport of some amino acids to the fetus. Changes in fetal plasma concentration and uptake of branched-chain amino acid appear to have no significant effect on fetal insulin or glucagon.
Reciprocal powered time model for release kinetic analysis of ibuprofen solid dispersions in oleaster powder, microcrystalline cellulose and crospovidone.

PURPOSE A physically sound derivation for reciprocal power time (RPT) model for kinetic of drug release is given. In order to enhance ibuprofen dissolution, its solid dispersions (SDs) prepared by cogrinding technique using crospovidone (CP), microcrystalline cellulose (MC) and oleaster powder (OP) as a novel carrier and the model applied to the drug release data. METHODS The drug cogrounds with the carriers were prepared and subjected to the dissolution studies. For elucidation of observed in vitro differences, FT-IR spectroscopy, X-ray diffraction patterns, DSC thermograms and laser particle size measurement were conducted. RESULTS All drug release data fitted very well to newly derived RPT model. The efficiency of the carriers for dissolution enhancement was in the order of: CP>OP>MC. The corresponding release kinetic parameter derived from the model, t50% (time required for 50% dissolution) for the carrier to drug ratio 2:1 were 2.7, 10.2 and 12.6 min, respectively. The efficiency of novel carrier, OP, was between CP and MC. FT-IR showed no interaction between the carriers and drug. The DSC thermograms and X-ray diffraction patterns revealed a slight reduced crystallinty in the SDs. Also grinding reduced mean particle size of drug from 150.7 to 44.4 microm. CONCLUSIONS An improved derivation for RPT model was provided which the parameter of the model, t50%, unlike to previous derivations was related to the most important property of the drug i.e. its solubility. The model described very well drug release kinetics from the solid dispersions. Cogrinding was an effective technique in enhancing dissolution rate of ibuprofen. Elaeagnus angostifolia fruit powder was suggested as a novel potential hydrophilic carrier in preparing solid dispersion of ibuprofen.
Racial Disparity in Colorectal Cancer: The Role of Equal Treatment

BACKGROUND: Racial disparity exists in colorectal cancer outcomes. The reasons for this are multifactorial. OBJECTIVE: The aim of this study was to evaluate the role of equal treatment of blacks and whites in the elimination of racial disparity in colorectal cancer outcomes. DESIGN: A retrospective cohort study of 878 patients with colorectal cancer diagnosed between 1998 and 2008 was done at a University tertiary referral center. Demographic variables including age, sex, and race were abstracted. Tumor-specific variables including American Joint Committee on Cancer stage, anatomic tumor location, vital status, and survival were obtained. Treatment-specific variables including surgery, chemotherapy, radiotherapy, and follow-up were also obtained. Racial differences in these variables were studied and their effect on overall survival was determined by using univariate and multivariate analyses. The findings were then compared with previous data from our institution. SETTING: University tertiary referral center. MAIN OUTCOME MEASURES: The primary outcomes measured were overall survival and cancer-specific mortality. RESULTS: A total of 878 patients met the inclusion criteria, 186 (21.2%) of whom were black. Blacks were significantly younger at diagnosis in comparison with whites, with a median (quartiles) age of 55 years (28–87) compared with 59 years (23–94) (p = 0.0012). Equal proportions of blacks (78.5%) and whites (79.2%) underwent surgery (p = 0.84), similar proportions of blacks (55.4%) and whites (60.8%) received chemotherapy (p = 0.18), and similar proportions of blacks (17.2%) and whites (20.5%) received radiation therapy (p = 0.31). There was no difference in overall survival or cancer-specific mortality between the 2 racial groups. Univariate analysis showed American Joint Committee on Cancer stage and surgery as the only statistically significant factors for overall survival. On multivariate analysis, stage, surgery, and chemotherapy were the only statistically significant factors. Race was not an independent determinant of survival. CONCLUSIONS: There were no differences in overall survival and cancer-related mortality between blacks and whites, and this may have resulted from identical treatment. The previously noted disparities in treatment and overall survival at our institution have disappeared.