Miracle-dz/UniFAR-FTUs huggingface dataset:
Drugs in the medical treatment of Cushing's syndrome

Cushing's syndrome is a complex endocrine condition with potential serious complications if untreated or inadequately treated. Transsphenoidal surgery with resection of a pituitary adenoma is successful in 75 – 80% of patients, but approximately 20 – 25% show persistence of Cushing's, and a similar proportion may experience recurrence within 2 – 4 years post-op. When surgery fails, medical treatment can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations while more definitive therapy becomes effective. We describe pharmacological approaches to the treatment of Cushing's syndrome. Drugs used to suppress cortisol secretion are mostly inhibitors of steroidogenesis. Ketoconazole, fluconazole aminoglutethimide, metyrapone, mitotane and etomidate are in that category. Ketoconazole is in current use while other drugs, although mostly available in the past, continue to have a potential role either alone or in combination. Drugs that suppress adrenocorticotropic hormone (ACTH) secretion are less popular as standard treatment and include cyproheptadine, valproic acid, cabergoline, somatostatin analogs, PPAR-γ agonists, vasopressin antagonists. Some of these drugs have been tested in limited clinical trials but there is potential therapeutic benefit in analogs with better specificity for the class of receptors present in ACTH-secreting tumors. A third category of drugs is glucocorticoid receptor antagonists. Mifepristone is currently being tested in clinical trials in patients with persistent or recurrent Cushing's disease and in patients with metastatic adrenal cortical carcinoma or ectopic ACTH syndrome not amenable to surgery. We also review replacement therapy after surgery and non-specific drugs to treat complications in patients with severe hypercortisol. The review provides a complete survey of the drugs used in the medical treatment of Cushing's, and new advances in the development of pituitary-active drugs as well as receptor blockers of glucocorticoid action. It also provides avenues for exploration of new drugs active on somatostatin, dopamine and vasopressin receptors. There are effective pharmacological agents capable of chronically reversing biochemical and clinical manifestations of hypercortisolemia in Cushing's syndrome but new drugs are needed with action at the pituitary level.
Ciprofloxacin Treatment in Preterm Neonates in Bangladesh: Lack of Effects on Growth and Development

Background: Quinolone-induced arthropathic toxicity in weight-bearing joints observed in juvenile animals during preclinical testing has largely restricted the routine use of ciprofloxacin in the pediatric age group. As histopathologic, radiologic and magnetic resonance imaging monitoring evidence has gathered supporting the safety of fluoroquinolones in children, many pediatricians have started to prescribe quinolones to some patients on a compassionate basis. Objective: The objective of this study was to ascertain the safety of ciprofloxacin in preterm neonates <33 weeks gestational age treated at Dhaka Shishu (Children) Hospital in Bangladesh. Methods: Long-term follow up was done to monitor the growth and development of preterm infants who were administered intravenous ciprofloxacin in the neonatal period. Ciprofloxacin was used only as a life-saving therapy in cases of sepsis produced by bacterial agents resistant to other antibiotics. Another group of preterm neonates with septicemia who were not exposed to ciprofloxacin, but effectively treated with other antibiotics and followed up, were matched with cases for gender, gestational age and birth weight and included as a comparison group. Forty-eight patients in the ciprofloxacin group and 66 patients in the comparison group were followed up for a mean of 24.7 ± 18.5 months and 21.6 ± 18.8 months, respectively. Results: No osteoarticular problems or joint deformities were observed in the ciprofloxacin group during treatment or follow up. No differences in growth and development between the groups were found. Conclusions: Ciprofloxacin is a safe therapeutic option for newborns with sepsis produced by multiply resistant organisms.
Biological Activities of RUNX 1 Mutants Predict Secondary Acute Leukemia Transformation from Chronic Myelomonocytic Leukemia and Myelodysplastic Syndromes

Purpose: Transcription factor RUNX1 is essential for normal hematopoiesis. High mutation frequencies of RUNX1 gene in chronicmyelomonocytic leukemia (CMML) andmyelodysplastic syndromes (MDS) have been described, whereas the biologic significances of the mutations were not investigated. Here, we aimed to correlate the biologic activities of the RUNX1 mutants with the clinical outcomes of patients. Experimental Design: We examined the mutational status of RUNX1 in 143MDS and 84 CMML patients. Then, we studied the DNA and CBFb binding abilities of all the RUNX1 mutants identified by using electrophoretic mobility shift assay and coimmunoprecipitation assay, and also determined their activities on target C-FMS gene induction by Western blotting and luciferase reporter assay. Using luciferase reporter assay, the relative biologic activities of each RUNX1 mutant could be quantified and correlated with the patient outcomes by statistical analyses. Results: We observed that most RUNX1 mutants had reduced abilities in DNA binding, CBFb heterodimerization, and C-FMS gene induction. The relative biologic activities of RUNX1 mutants were grouped into highand low-activity mutations. Correlation of the activities of RUNX1 mutants with the clinical outcomes revealed that patients harboring lower activities of RUNX1 mutants had a higher risk and shorter time to secondary acute myeloid leukemia transformation in MDS and CMML. In multivariate analysis, low RUNX1 activity remained an independent predictor for secondary acute myeloid leukemia–free survival in MDS patients. Conclusions: The biologic activity rather than the mutational status of RUNX1 might be an indicator in predicting outcome of patients with MDS and CMML. Clin Cancer Res; 21(15);
Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics

Cytochrome P450 (CYP) 2D6 is expressed in liver, brain and other extrahepatic tissues where it metabolizes a range of centrally acting drugs and toxins. As ethanol can induce CYP2D in rat brain, we hypothesized that CYP2D6 expression is higher in brains of human alcoholics. We examined regional and cellular expression of CYP2D6 mRNA and protein by RT‐PCR, Southern blotting, slot blotting, immunoblotting and immunocytochemistry. A significant correlation was found between mean mRNA and CYP2D6 protein levels across 13 brain regions. Higher expression was detected in 13 brain regions of alcoholics (n = 8) compared to nonalcoholics (n = 5) (anovap < 0.0001). In hippocampus this was localized in CA1–3 pyramidal cells and dentate gyrus granular neurons. In cerebellum this was localized in Purkinje cells and their dendrites. Both of these brain regions, and these same cell‐types, are known to be susceptible to alcohol damage. For one case, a poor metabolizer (CYP2D6*4/*4), there was no detectable CYP2D6 protein, confirming the specificity of the antibody used. These data suggest that in alcoholics elevated brain CYP2D6 expression may contribute to altered sensitivity to centrally acting drugs and to the mediation of neurotoxic and behavioral effects of alcohol.
Video object segmentation aggregation

We present an approach for unsupervised object segmentation in unconstrained videos. Driven by the latest progress in this field, we argue that segmentation performance can be largely improved by aggregating the results generated by state-of-the-art algorithms. Initially, objects in individual frames are estimated through a per-frame aggregation procedure using majority voting. While this can predict relatively accurate object location, the initial estimation fails to cover the parts that are wrongly labeled by more than half of the algorithms. To address this, we build a holistic appearance model using non-local appearance cues by linear regression. Then, we integrate the appearance priors and spatio-temporal information into an energy minimization framework to refine the initial estimation. We evaluate our method on challenging benchmark videos and demonstrate that it outperforms state-of-the-art algorithms.
Effect of toothbrushing on acrylic resin veneering material. II. Abrasive effect of selected dentifrices and toothbrushes.

The abrasiveness of selected dentifrices and toothbrushes was studied with a toothbrushing machine. Test specimens of acrylic resin material were brushed for 60 minutes. The surface irregularities of the specimen were measured in a Talysurf instrument and the microwaves were studied in a scanning electron microscope. The weight reduction of the specimen was recorded and found to be correlated with a quality value of the irregularities in the test surface (CLA). — The abrasiveness of the dentifrices displayed a wide range, the lowest values being recorded for a dentifrice with methylmetacrylate as abrasive agent, the highest with calcium carbonate as abrasive agent. The abrasiveness of the toothbrushes likewise showed a wide range. Significant differences were recorded between «hard« and «soft« brushes with bristles of nylon, while the corresponding difference for natural bristle material was slight. All the toothbrushes and all but one of the dentifrices studied caused undesirable abrasive effects on the .
Subfornical organ lesion attenuates chronic hypotensive effects of losartan in salt-replete rats

Hypothesis/introduction Circumventricular organs are central nervous system brain sites thought to participate in neuroendocrine regulation of neural output. We have previously demonstrated a profound chronic hypotensive response to the angiotensin II (Ang II) AT1 antagonist, losartan (10 mg/kg/day), in normal rats. In addition, we have demonstrated that the area postrema, one of the circumventricular organs, partially mediates this response. The subfornical organ (SFO) is another circumventricular organ which has been shown to mediate actions of Ang II. The present study was designed to test the hypothesis that the SFO mediates the chronic hypotensive effects of losartan in normal rats. Materials and methods Rats were randomly chosen for lesion of the SFO or sham operation and instrumented with intravenous catheters and radiotelemetric blood pressure transducers. After a control period, rats were infused with losartan (10 mg/kg/day) for nine days. Mean arterial pressure and heart rate responses were measured continuously throughout the protocol and examined as 12-hour day/night averages. Results By day 7 of losartan treatment, night-time mean arterial pressure had dropped to 75±2 mmHg in sham rats (n=8) but only to 83±2 mmHg in SFO-lesioned rats (n=10). This trend continued throughout the treatment protocol. Conclusions These results suggest that the SFO partially mediates the chronic hypotensive effects of chronic losartan treatment in normal rats.
Management of the posterior maxilla in the compromised patient: historical, current, and future perspectives.

Anatomic factors include decreased bone quantity, especially in older edentulous or partially edentulous patients who have experienced alveolar resorption in the wake of tooth loss. The antrum also tends to enlarge with age, as well as with edentulism, and this further decreases the amount of available bone. In addition to the diminished quantity, bone in the posterior maxilla often is softer and of poorer quality. Radiographs typically reveal a dearth of trabeculations, and the tactile experience of drilling here often more closely resembles the penetration of styrofoam rather than anthracite. Limited access to the pterygomaxillary region constitutes yet another problem.
Evaluation of Bone Scan as a Screening Work‐up in Primary and Local‐Regional Recurrence of Breast Cancer

To evaluate the use of radionuclide bone scan in staging patients with primary and local-regional recurrence of breast cancer, we reviewed the results in 265 patients with primary breast cancer who had the scan either preoperatively or within 6 weeks of surgery, and in 39 patients presenting with their first local-regional recurrence. All patients were clinically staged according to the revised 1983 criteria of the American Joint Committee for Cancer Staging and End-Results Reporting. None of the 92 with stage I and four of 95 patients with stage II had a positive scan. Eleven of 41 with stage IIIA and 13 of 37 with stage IIIB had a positive bone scan. In patients with their first local-regional recurrence, 12 of 39 had a positive scan. Follow-up scans were available in 61 patients with clinical stage I and II breast cancer who had adjuvant chemotherapy for pathological involvement of axillary node. There were six conversions observed in 61 scans obtained during the first year. Seven converted in follow-up scans in 47 patients in the second year. We conclude that although bone scans have a low positive yield in stage I and II breast cancer, their use in the preoperative setting and in the follow-up of patients with axillary node involvement detects early converters. Bone scans are justified in stage IIIA and IIIB breast cancer and in patients being evaluated for local-regional recurrence.
Analysis of B 10.D2 Recombinant Congenic Mouse Strains Shows That Audiogenic and β‐CCM‐Induced Seizures Depend on Different Genetic Mechanisms

Summary: The rate of occurrence of audiogenic seizures and seizures induced by the benzodiazepine receptor inverse agonist methyl‐β‐carboline‐3‐carboxylate (β‐CCM) were analyzed in several recombinant congenic strains of mice bred from B10.D2 and DBA/2J. Although both types of seizures have similar behavioral patterns and might involve GABAergic mechanisms, no correlation was observed between the occurrence of the two types of seizures across the strains, suggesting that these two types of seizures depend on different genetic mechanisms.
Social Factors in User Perceptions and Responses to Advertising in Online Social Networking Communities

ABSTRACT With the advent of popular Web destinations such as MySpace and Facebook, online social networking communities now occupy the center stage of e-commerce. Yet these online social networking communities must balance the trade-off between advertising revenue and user experience. Drawing on the sociology and advertising literature, this study investigates the impacts of social identity and group norms on community users’ group intentions to accept advertising in online social networking communities. By outlining how this type of group intention could influence community members’ perceptions and value judgments of such advertising, this study delineates possible mechanisms by which community members may respond positively to community advertising. The authors test the proposed theoretical framework on a sample of 327 popular online community users in China and obtain general support. Implications for the prospect of advertising in online social networking communities are discussed.
Ethnic density, physical illness, social deprivation and antidepressant prescribing in primary care: ecological study.

BACKGROUND Antidepressant prescribing should reflect need. The Quality and Outcomes Framework has provided an opportunity to explore factors affecting antidepressant prescribing in UK general practice. AIMS To explore the relationship between physical illness, social deprivation, ethnicity, practice characteristics and the volume of antidepressants prescribed in primary care. METHOD This was an ecological study using data derived from the Quality and Outcomes Framework, the Informatics Collaboratory of the Social Sciences, and Prescribing Analyses and CosT data for 2004-2005. Associations were examined using linear regression modelling. RESULTS Socio-economic status, ethnic density, asthma, chronic obstructive pulmonary disease and epilepsy explained 44% of the variance in the volume of antidepressants prescribed. CONCLUSIONS Lower volumes of antidepressants are prescribed in areas with high densities of Black or Asian people. This may suggest disparities in provision of care. Chronic respiratory disease and epilepsy may have a more important association with depression in primary care than previously thought.
Consideration of sheep as a minor species: comparison of drug metabolism and disposition with other domestic ruminants.

The processes which determine bioequivalence of a given drug among species are many, and include absorption from a site of administration, renal, biliary and intestinal elimination, sequestration (in particular, binding to proteins or other macromolecules), distribution and redistribution, biotransformation, and receptor population density and uniqueness. The present review is limited to physiologic and pharmacologic parameters which affect drug distribution, elimination, and metabolism, primarily because these are areas where sufficient data is available to make comparisons between sheep and other ruminants. The literature suggest a high degree of similarity among domestic ruminants in the distribution and elimination of drugs that are not metabolized but eliminated by passive processes such as renal glomerular filtration. Although the data are not as uniform as when conducted under rigorous control in the same laboratory setting, it is possible to predict very similar pharmacokinetic profiles for many of the antimicrobials between cattle, sheep and goats. Metabolic scaling of kinetic parameters could be predicted in comparative studies conducted under well-controlled conditions, in which case the greatest similarities would occur among the small ruminants with values being somewhat dissimilar between sheep or goats and cattle. Plasma protein binding of drugs appears to be very similar among the ruminants, and its influence on drug distribution and elimination does not appear to vary appreciably between cattle and sheep. There is, however, very little definitive data which describes binding parameters, and there is very little data of any kind on binding to caprine albumin other plasma proteins of the goat. Sheep apparently differ from cattle, however, in transcortin concentrations, and this could affect the distribution and elimination of prednisolone or any other synthetic steroid which exhibits high affinity binding to this transport protein. Among the drug substances for which comparative information is available, there is very little to suggest qualitative differences in routes of metabolism among ruminants. There appears to be a remarkable degree of similarity in both major and minor pathways of drug metabolism among these species, and in fact, no documentable differences of a qualitative nature have been found. It should be noted, however, that documentable differences would only be established in a direct comparison of species conducted in the same laboratory under carefully controlled conditions. Such conditions would necessarily include assurance of no recent exposure to enzyme inducing agents or inhibitors or to agents which could deplete endogenous substances necessary to the enzymatic process. (ABSTRACT TRUNCATED AT 400 WORDS)
The quorum‐sensing protein TraR of Agrobacterium tumefaciens is susceptible to intrinsic and TraM‐mediated proteolytic instability

TraR of Agrobacterium tumefaciens is a LuxR‐type transcription factor that regulates genes required for replication and conjugation of the tumour‐inducing plasmid. TraR binds the pheromone 3‐oxo‐octanoylhomoserine lactone (OOHL) and requires this molecule for folding into a protease‐resistant, soluble conformation. Even after binding to OOHL, TraR is degraded at readily detectable rates. Here we show that the N‐terminal domain of TraR, which binds OOHL, is more resistant to degradation than the full length protein, suggesting that sites on the C‐terminal DNA binding domain [TraR(170–234)] enhance protein turnover. A fusion between GFP and TraR(170–234) was poorly fluorescent, and truncations of this fusion protein allowed us to identify residues in this domain that contribute to protein degradation. TraR activity was previously shown to be inhibited by the antiactivator TraM. These proteins form 2:2 complexes that fail to bind DNA sequences. Here we show that TraM sharply decreased the accumulation of TraR in whole cells, indicating that TraM facilitates proteolysis of TraR. The TraM component of these complexes is spared from proteolysis, and could therefore act catalytically.
LYSSAVIRUS IN EPTESICUS SEROTINUS (CHIROPTERA: VESPERTILIONIDAE)

To determine the prevalence of European Bat Lyssavirus 1 (EBL1), antibodies plasma samples were obtained from 175 serotine bats (Eptesicus serotinus) from four colonies in southern Spain between September of 1991 and September 1992. Five bats were detected with EBL1 virus in one colony in 1989. The prevalence of antibodies rose to 74% in one of the colonies studied (Villarrasa) in the spring of 1992. After a few months the prevalence declined to under 10%. Individuals with a high antibody level in the spring (up to ED50 = 280) had very low titers or no antibodies in the following summer and autumn.
Safety and immunogenicity of a vaccine targeting human papillomavirus types 6, 11, 16 and 18: a randomized, placebo-controlled trial in 176 Korean subjects

Human papillomavirus (HPV) is a major causative agent of anogenital warts and a necessary cause of cervical cancer. This report will serve to assess the safety and immunogenicity of quadrivalent (types 6, 11, 16, and 18) HPV L1 virus-like particle (VLP) vaccine in the Korean population. We performed a randomized, double-blind, placebo-controlled study in 176 volunteers aged 9–23 years. Using a 2:1 ratio for randomization, 117 women were assigned to quadrivalent HPV (20 μg type 6, 40 μg type 11, 40 μg type 16, and 20 μg type 18) vaccine and 59 women to placebo. Individuals received vaccine at day 1, month 2, and month 6 and provided blood samples for analysis at enrollment at month 7. Analyses were done as specified in the study protocol. Quadrivalent HPV vaccine was generally well tolerated, with no vaccine-related serious adverse experiences. Quadrivalent HPV vaccine induced seroconversion for each vaccine-related HPV type. At month 7, vaccine-induced type-specific antibody titer was high. In conclusion, administration of quadrivalent HPV VLP vaccine to Korean women aged 9–23 years was generally well tolerated and highly immunogenic
"Mummies and babies" and friends and lovers in Lesotho.

This paper examines an institutionalized friendship among adolescent girls and young women in southern Africa. Lesotho's economy is based on migrant male labor which leaves the women dependent on male earnings or subsistence from the land, and also creates unstable marital relations. Young girls in the modern schools develop close relationships, called "mummy-baby," with slightly older girls. Sexual intimacy is an important aspect of these relationships. Mummy-baby relationships not only provide emotional support prior to marriage, but also a network of support for married and unmarried women in new towns or schools, either replacing or accompanying heterosexual bonds.