Miracle-dz/UniFAR-FTUs huggingface dataset:
The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey.

PURPOSE To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 +/- 0.20 vs. 0.53 +/- 0.18 microL.min(-1). After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.
The NQO1 C609T polymorphism and risk of lung cancer: a meta-analysis.

OBJECTIVE NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two- electron reduction of quinoid compounds into hydroquinones. A single base substitution (C? T) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Published data on the association between NQO1 C609T polymorphism and lung cancer risk are conflicting. METHODS To derive a more precise estimation of the relationship, a meta-analysis was performed. RESULTS A total of 23 studies including 5,575 cases and 9,132 controls were assessed. The pooled result showed that the NQO1 polymorphism was not associated with a clear increased risk of lung cancer (OR = 1.009, 95% CI: 0.943-1.078; P heterogeneity=0.049). In the subgroup analysis by ethnicity, no clear increased risk was found among Asians for TT/CT versus CC (OR = 1.005; 95% CI = 0.890-1.135; P heterogeneity=0.024). However, the TT and CT genotypes combined were associated with significantly increased risk of lung cancer in Chinese (OR = 1.237, 95% CI: 1.029-1.486; P heterogeneity=0.061) among whom the variant allele is common. The variant genotype of NQO1 was also associated with modestly increased risk of lung cancer among white populations (OR = 1.017, 95% CI: 0.936-1.105; P heterogeneity=0.101). However, no significant association was found in Africans with all genetic models. CONCLUSIONS Our meta-analysis suggests that the variant NQO1 C609T genotype may affect individual susceptibility to lung cancer. This meta- analysis suggests that the NQO1 609T allele is a low penetrant risk factor for developing lung cancer in Chinese.
Evaluation of Prevalence and Severity of Malocclusion in South Travancore Population

Background: Assess prevalence and severity of malocclus ion in 12 – 16 year old population of Travancore using IOTN index. Tertiary care setting, with the study being conducted in the Dept of Orthodontics at PMS Dental College & the samples being collected from four different dental health care centres. Study design is descriptive study. Materials and Methods: 120 pre- treatment study models of patients aged 12-16 yrs were collected, 30 each from four dental health centres spread across the state. These casts were subjected to three stages of screening based on IOTN index to arrive at the prevalence and severity of malocclusion in the targeted group. Kappa statistics and stratified kappa statistics. Results: Results of the study showed that the prevalence of malocclusion and treatment need was 53.3%. Conclusions: The prevalence of orthodontic treatment need in South Kerala was found to be 53.3%.
Metagenomic Assembly using Coverage and Evolutionary distance ( MACE )

Recent advances in accuracy and cost of whole-genome shotgun sequencing have opened up various fields of study for biologists. One such field is that of metagenomics – the study of the bacterial biome in a given sample. The human body, for example, has approximately 10 bacterial cells for every native cell, and lack of certain strains may contribute to prevalence of diseases such as obesity, Crohn’s disease, and type 2 diabetes. Although the field of metagenomics is very promising, as with any new field, there are many difficulties with such analyses.
Failed obstetric tracheal intubation and postoperative respiratory support with the ProSeal laryngeal mask airway.

UNLABELLED The ProSeal laryngeal mask airway (ProSeal LMA) provides a better seal and probably better airway protection than the classic laryngeal mask airway (classic LMA). We report the use of the ProSeal LMA in a 26-yr-old female with HELLP syndrome for failed obstetric intubation and postoperative respiratory support. Both laryngoscope-guided tracheal intubation and face mask ventilation failed, but a size 4 ProSeal LMA was easily inserted and high tidal volumes obtained. A gastric tube was inserted through the ProSeal LMA drain tube and 300 mL of clear fluid was removed from the stomach. There were no hemodynamic changes during ProSeal LMA insertion. Postoperatively, the patient was transferred to the intensive care unit, where she was ventilated via the ProSeal LMA for 8 h until the platelet count had increased and she was hemodynamically stable. Weaning and ProSeal LMA removal were uneventful. There is anecdotal evidence supporting the use of the LMA devices for failed obstetric intubation (19 cases) and for postoperative respiratory support (8 cases). In principle, the ProSeal LMA may offer some advantages over the classic LMA in both these situations. IMPLICATIONS We report the successful use of the ProSeal laryngeal mask airway for failed obstetric intubation and postoperative respiratory support in a patient with HELLP syndrome.
Histopathologic evaluation of aneurysms treated with Guglielmi detachable coils or matrix detachable microcoils.

BACKGROUND AND PURPOSE The purpose of this study was to evaluate the degree of organization and fibrocellular tissue development in aneurysms treated with bare platinum or biologically active microcoils. METHODS Twelve aneurysms were removed at autopsy between 1-18 days and another 2 between 2-3 months posttreatment. Four aneurysms were surgically removed between 6 months and 3 years following treatment. One aneurysm removed at 8 days and another at 6 months were treated with bioactive (Matrix) coils; the other 16 with bare platinum (Guglielmi detachable coils; GDCs). All specimens were embedded in plastic, stained with hematoxilin-eosin and elastin and examined by light microscopy. RESULTS All specimens removed within 3 weeks demonstrated intra-aneurysmal thrombus, without signs of organization or fibrotic tissue formation over the neck regardless of the type of coils used. In the GDC-treated aneurysms, evidence of early thrombus organization was observed within 2-3 months, and completed yet imperfect fibrocellular reaction together with residual thrombus at 2-3 years. In the Matrix-treated specimens, the aneurysm cavity was completely filled with granulation tissue corresponding to still ongoing fibrocellular reaction at 6 months, including newly formed blood vessels, smooth muscle cells, and collagen deposition without signs of residual thrombus. CONCLUSIONS Our results indicate that in aneurysms treated with bare platinum coils thrombus organization does not occur until late after treatment and may remain imperfect for years. In one aneurysm studied 8 days following treatment with Matrix coils, no difference was noted compared to aneurysms treated with bare platinum coils. In another aneurysm examined 6 months following packing with Matrix coils, the histologic changes support the hypothesis that the biologically active polymer may accelerate aneurysm healing.
Differential curvature sensing and generating activities of dynamin isoforms provide opportunities for tissue-specific regulation

Dynamin 1 (Dyn1) and Dyn2 are neuronal and ubiquitously expressed isoforms, respectively, of the multidomain GTPase required for clathrin-mediated endocytosis (CME). Although they are 79% identical, Dyn1 and Dyn2 are not fully functionally redundant. Through direct measurements of basal and assembly-stimulated GTPase activities, membrane binding, self-assembly, and membrane fission on planar and curved templates, we have shown that Dyn1 is an efficient curvature generator, whereas Dyn2 is primarily a curvature sensor. Using Dyn1/Dyn2 chimeras, we identified the lipid-binding pleckstrin homology domain as being responsible for the differential in vitro properties of these two isoforms. Remarkably, their in vitro activities were reversed by a single amino acid change in the membrane-binding variable loop 3. Reconstitution of KO mouse embryo fibroblasts showed that both the pleckstrin homology and the Pro/Arg-rich domains determine the differential abilities of these two isoforms to support CME. These domains are specific to classical dynamins and are involved in regulating their activity. Our findings reveal opportunities for fundamental differences in the regulation of Dyn1, which mediates rapid endocytosis at the synapse, vs. Dyn2, which regulates early and late events in CME in nonneuronal cells.
Survival After Repair of Postinfarction Ventricular Septal Defects in Patients Over the Age of 70

Ventricular septal defect (VSD) is an infrequent but extremely serious complication of myocardial infarction. Operative mortality rates tend to be higher in the elderly population; however, long‐term follow‐up has not been specifically studied. It is, therefore, important to assess not only the early but also the long‐term results of VSD repair in patients over 70 years of age to determine its value for the elderly patient. Between June 1968 and May 1991, 86 patients who experienced a myocardial infarction underwent surgical repair of an infarct related VSD at the Massachusetts General Hospital (MGH). Group I (n = 57) includes those patients younger than 70 years, and group II (n = 29) represents those patients age 70 years and older. Follow‐up of hospital survivors ranged from 1 month to 24 years and was compiled in April and May, 1991. Three patients were lost to follow‐up (4%), and these were younger than 70 years of age. There were no differences in the values of the preoperative variables for the younger and older groups with respect to sex, concomitant procedures performed (bypass vs no bypass), use of an intraaortic balloon pump (IABP), location of VSD, presence of shock, total hospital days, or days between infarction and operation. There was, however, a difference between the two groups relative to the era when surgery was performed. More patients over the age of 70 underwent surgery after 1978 than before 1978 (p = 0.0012). The majority of survivors are in New York Heart Association (NYHA) Class I or II, and there was no difference between the younger and older groups in functional class at the time of follow‐up (83.3% vs 91.7% of survivors in Class I or II, respectively). Using the generalized Wilcoxon test to analyze these survival data, there was no apparent difference in long‐term survival (p = 0.97) when comparing the two age groups. The mean follow‐up period was 77.02 months for the younger group and 80.52 months for the older group. The fact that more older patients were repaired after we had significant experience in the surgical management of patients with VSDs probably accounted for our excellent results in the older age group. Our data reveal that patients over the age of 70 can expect excellent long‐term survival, with over 90% of these survivors remaining in NYHA Functional Class I or II.
Assessment of Cognitive Behavioral Therapy on Quality of Life of Patients with Chronic War-related Post-traumatic Stress Disorder

Background: Post-traumatic stress disorder (PTSD) is the one of the most commonly observed psychiatric disorder in veterans. The condition can lead to considerable social, occupational, and interpersonal dysfunction. PTSD occurring after combat injury appears to be strongly correlated with the extent of injury, and develops over several months. Present study was designed for assessing the cognitive behavioral therapy in the quality of life (QOL) of war-related PTSD in veterans compared to control group and compare applied treatments with each other. Materials and Methods: In the present study, we assessment effects of cognitive behavioral therapy such as problem solving, exposure therapy and their combination on QOL in 120 Iranian PTSD patients veterans after Iran-Iraq war. They were randomly allocated to one of four equal interventional groups: (a) Problem solving therapy (b) exposure therapy (c) combined therapy (exposure therapy plus problem solving) (d) control group. Before and after study intervention, patients were evaluated by short form-36 (SF-36) questionnaire. Results: Post-test and follow-up SF-36 scores were 55.6±4 and 55.1±3.6 in exposure therapy, 50±4.4 and 56.1±3.8 in problem solving, and 48.73±3.8 and 50.9±4.2 in combined therapy. In comparing to control group, all intervention showed significant improvement in QOL in PTSD patients. Conclusion: According to the results of the present study, behavioral therapy can improve QOL in PTSD patients.
A Touch Probe Method of Operating an Implantable RFID Tag for Orthopedic Implant Identification

The major problem in operating an implantable radio-frequency identification (RFID) tag embedded on an orthopedic implant is low efficiency because of metallic interference. To improve the efficiency, this paper proposes a method of operating an implantable passive RFID tag using a touch probe at 13.56 MHz. This technology relies on the electric field interaction between two pairs of electrodes, one being a part of the touch probe placed on the surface of tissue and the other being a part of the tag installed under the tissue. Compared with using a conventional RFID antenna such as a loop antenna, this method has a better performance in the near field operation range to reduce interference with the orthopedic implant. Properly matching the touch probe and the tag to the tissue and the implant reduces signal attenuation and increases the overall system efficiency. The experiments have shown that this method has a great performance in the near field transcutaneous operation and can be used for orthopedic implant identification.
Immunotherapy of cancer using heat shock proteins.

Tumor derived heat shock protein (hsp)-peptide complexes (particularly hsp70 and grp94/gp96) have been demonstrated to serve as effective vaccines, producing anti-tumor immune responses in animals and in man. This approach utilizes the peptide binding properties of stress proteins which are responsible for their functions as molecular chaperones in numerous cellular processes. The present review briefly introduces the reader to the basic stress protein families, i.e. heat shock and glucose regulated proteins, their regulation, compartmentalization and family members. It then introduces the reader to aspects of hsps/grp function and interactions with the host's immune system. An overview of the conventional uses of hsp/grp vaccines as autologous vaccines derived from cancers is presented. We then discuss other stress protein related vaccination approaches. This includes the use of recombinant antigens, both proteins and peptides, naturally complexed to hsp/grps; hsp/grp DNA vaccines, hsp/grp fusion proteins and cell based hsp/grp vaccines. The advantages and disadvantages of each vaccination approach are discussed. Lastly, means of further enhancing the already potent activity of stress protein vaccines are presented, specifically the use of hyperthermia or CTLA-4 blockade as adjuvants.
Dependence of exhaled breath composition on exogenous factors, smoking habits and exposure to air pollutants

Non-invasive disease monitoring on the basis of volatile breath markers is a very attractive but challenging task. Several hundreds of compounds have been detected in exhaled air using modern analytical techniques (e.g. proton-transfer reaction mass spectrometry, gas chromatography-mass spectrometry) and have even been linked to various diseases. However, the biochemical background for most of compounds detected in breath samples has not been elucidated; therefore, the obtained results should be interpreted with care to avoid false correlations. The major aim of this study was to assess the effects of smoking on the composition of exhaled breath. Additionally, the potential origin of breath volatile organic compounds (VOCs) is discussed focusing on diet, environmental exposure and biological pathways based on other's studies. Profiles of VOCs detected in exhaled breath and inspired air samples of 115 subjects with addition of urine headspace derived from 50 volunteers are presented. Samples were analyzed with GC-MS after preconcentration on multibed sorption tubes in case of breath samples and solid phase micro-extraction (SPME) in the case of urine samples. Altogether 266 compounds were found in exhaled breath of at least 10% of the volunteers. From these, 162 compounds were identified by spectral library match and retention time (based on reference standards). It is shown that the composition of exhaled breath is considerably influenced by exposure to pollution and indoor-air contaminants and particularly by smoking. More than 80 organic compounds were found to be significantly related to smoking, the largest group comprising unsaturated hydrocarbons (29 dienes, 27 alkenes and 3 alkynes). On the basis of the presented results, we suggest that for the future understanding of breath data it will be necessary to carefully investigate the potential biological origin of volatiles, e.g., by means of analysis of tissues, isolated cell lines or other body fluids. In particular, VOCs linked to smoking habit or being the results of human exposure should be considered with care for clinical diagnosis since small changes in their concentration profiles (typically in the pptv–ppbv range) revealing that the outbreak of certain disease might be hampered by already high background.
Autophagy is activated, but is not required for the G0 function of BCL-2 or BCL-xL

Cell cycle arrest in G0 and autophagy have features in common, but the inter-relationship between the two processes is not well defined. The anti-apoptosis molecules BCL-2 and BCL-xL promote G0 arrest through upregulation of p27 protein, which can also induce autophagy. We tested the hypothesis that autophagy was involved in the cell cycle arrest function of BCL-2 and BCL-xL. We found that in IL-3-dependent FL5.12 cells, NIH3T3 cells, and mouse embryo fibroblasts induced to arrest, treatment with 3-methyladenine did not affect the expected decrease in cell size and ribosomal RNA synthesis, or upregulation of p27 levels. Using the m5-7 ATG5-/- MEF cell line with doxycycline-regulated ATG5 expression, we demonstrated that autophagy was activated during serum withdrawal and contact inhibition, but inhibition of autophagy had no measurable effect on G0 arrest in parental or BCL-xL-expressing cells. Thus, our data indicate that, in cell culture models, autophagy occurs but is not required for entrance into quiescence or for the G0 function of BCL-2 or BCL-xL.
Three‐dimensional dynamic liver MR imaging using sensitivity encoding for detection of hepatocellular carcinomas: Comparison with superparamagnetic iron oxide‐enhanced MR imaging

To assess the diagnostic performance of three‐dimensional dynamic liver imaging with sensitivity encoding (SENSE), including double arterial phase images and increased resolution, by comparing it to superparamagnetic iron oxide (SPIO)‐enhanced magnetic resonance (MR) imaging for the detection of hypervascular hepatocellular carcinoma (HCC).
Challenges of building community-university partnerships in new poverty landscapes

Abstract This article reflects on six years of community–university partnerships (CUPs) between the Charlotte Action Research Project (CHARP), grassroots organizations, and residents of economically challenged neighborhoods in Charlotte, NC. We share lessons learned in participatory planning and community development by comparing experiences in older, urban neighborhoods with those in suburban, “new poverty landscapes. ” We highlight neighborhood typology, residents’ choices to leave, place attachment, and sociospatial and geographic context as defining factors within CUPs. A grounded framework for evaluating CUPs is introduced, and a synthesis of interviews and CHARP archives provide insight into what to do best, and in what conditions, in partnership efforts. We conclude that community-based research should always start by listening and that sometimes moving to action research makes sense, while at other times an advocacy research route is more appropriate. We assert that the most challenged neighborhoods, despite a lack of capacity and readiness, must not be avoided.
Regulation of Focal Adhesion Kinase Activation, Breast Cancer Cell Motility, and Amoeboid Invasion by the RhoA Guanine Nucleotide Exchange Factor Net1

ABSTRACT Net1 is a RhoA guanine nucleotide exchange factor (GEF) that is overexpressed in a subset of human cancers and contributes to cancer cell motility and invasion in vitro. However, the molecular mechanism accounting for its role in cell motility and invasion has not been described. In the present work, we show that expression of both Net1 isoforms in breast cancer cells is required for efficient cell motility. Although loss of Net1 isoform expression only partially blocks RhoA activation, it inhibits lysophosphatidic acid (LPA)-stimulated migration as efficiently as knockdown of RhoA itself. However, we demonstrate that the Net1A isoform predominantly controls myosin light-chain phosphorylation and is required for trailing edge retraction during migration. Net1A interacts with focal adhesion kinase (FAK), localizes to focal adhesions, and is necessary for FAK activation and focal adhesion maturation during cell spreading. Net1A expression is also required for efficient invasion through a Matrigel matrix. Analysis of invading cells demonstrates that Net1A is required for amoeboid invasion, and loss of Net1A expression causes cells to shift to a mesenchymal phenotype characterized by high β1-integrin activity and membrane type 1 matrix metalloproteinase (MT1-MMP) expression. These results demonstrate a previously unrecognized role for the Net1A isoform in controlling FAK activation during planar cell movement and amoeboid motility during extracellular matrix (ECM) invasion.