Miracle-dz/UniFAR-FTUs huggingface dataset:
Should combination therapy with inhaled corticosteroids and long-acting beta2-agonists be prescribed as initial maintenance treatment for asthma?

In March of this year, GlaxoSmithKline (GSK) received approval from Health Canada for a revised product monograph with a new indication for the use of Advair, an aerosol containing both salmeterol, a long-acting β2-agonist, and fluticasone, an inhaled corticosteroid for use in patients with asthma
Evaluating the Implementation of an Interdisciplinary Evidence-Based Practice Educational Program in a Large Academic Medical Center

The purpose of this study was to create a system-wide education program in a large academic medical center to increase exposure and understanding of the evidence-based practice (EBP) process with multidisciplinary healthcare professionals. We also hoped to increase their confidence in utilizing and implementing EBP at the bedside. Although our approach to educating professional staff on EBP provided initial benefits, holding the gains over a 1-year period proved to be difficult.
Compositional Determinants of Mechanical Properties of Enamel

Dental enamel is comprised primarily of carbonated apatite, with less than 1% w/w organic matter and 4–5% w/w water. To determine the influence of each component on the microhardness and fracture toughness of rat incisor enamel, we mechanically tested specimens in which water and organic matrix were selectively removed. Tests were performed in mid-sagittal and transverse orientations to assess the effect of the structural organization on enamel micromechanical properties. While removal of organic matrix resulted in up to a 23% increase in microhardness, and as much as a 46% decrease in fracture toughness, water had a significantly lesser effect on these properties. Moreover, removal of organic matrix dramatically weakened the dentinoenamel junction (DEJ). Analysis of our data also showed that the structural organization of enamel affects its micromechanical properties. We anticipate that these findings will help guide the development of bio-inspired nanostructured materials for mineralized tissue repair and regeneration.
A tribute to Ernst Mayr

© Zoo Outreach Organisation; www.zoosprint. org Manuscript 1345a; Received 22 March 2005; Finally accepted 1 April 2005; Date of publication 21 April 2005 1851 May 2005 Ernst Mayr, the great evolutionist and systematist of the 20th century, celebrated his 100th birthday in July 2004, and breathed his last in February 2005. He remained academically active throughout his long life, and authored nearly 700 papers and 25 books, the last book appearing in 2004. Commenting on his mental vigour and scientific
THE VINCA ALKALOIDS: A NEW CLASS OF ONCOLYTIC AGENTS.

Summary A phytochemical investigation of the plant Vinca rosea Linn. has demonstrated that a number of alkaloidal substances can be obtained with antitumor activity. Over 30 alkaloids have been obtained, of which four—vinblastine, vinleurosine, vincristine, and vinrosidine—are known definitely to be active. Chemically these compounds are closely related to one another and to two monomeric alkaloids, vindoline and catharanthine. The structure of these latter two compounds has been determined, and partial structures for the biologically active alkaloids have been proposed. They represent a new class of large complex dimeric alkaloids containing both indole and dihydroindole moieties. Experimentally, a strain-specific, transplantable, acute, lymphocytic leukemia (P-1534) carried in DBA/2 mice served as a bioassay for obtaining these compounds and for predicting their clinical activity. Vinblastine, vincristine, and vinrosidine are capable of prolonging and/or “curing” mice of the P-1534 leukemia even when therapy is delayed until a near-terminal state of generalized disease. Resistance to an additional challenge of leukemic cells has been observed in these “cured” animals. Parenteral administration of vincristine has been demonstrated to “cure” mice given intracranial implants of the P-1534. The experimental tumor spectrum and toxicological studies are presented and discussed. Biochemical studies performed to date do not reveal any effect on cellular respiration, glycolysis, protein or nucleic acid synthesis. The mechanisms of action of these compounds, which may differ within the group as well as from those of other known agents, remain to be determined. Only two of these compounds, vinblastine and vincristine, have received extensive clinical evaluation. In spite of their close similarity, chemically, a somewhat different group of human neoplasms responds to these compounds, and there has been a singular lack of cross-resistance between these two drugs and any other oncolytic drug now in wide use. Vinblastine has proved effective in chorioepithelioma, Hodgkin9s disease, and other lymphomas, and a number of beneficial results have been obtained in carcinoma of the breast and bronchus. In addition, there have been smaller numbers of a variety of other neoplasias reported as responding to this compound. Vincristine has been striking in its ability to induce complete hematological remission of the acute leukemias of childhood, both lymphocytic and myelogenous in type. Responses have also been reported in a number of other malignancies. The problems and obstacles encountered in obtaining a full realization of the clinical efficacy of these new types of oncolytic compounds are discussed in addition to areas of clinical application other than those previously reported.
Training multitasking in a virtual supermarket: a novel intervention after stroke.

OBJECTIVE To explore the potential of the VMall, a virtual supermarket running on a video-capture virtual reality system, as an intervention tool for people who have multitasking deficits after stroke. METHOD Poststroke, 4 participants received ten 60-min sessions over 3 weeks using the VMall. The intervention focused on improving multitasking while the participant was engaged in a virtual shopping task. Instruments included the Multiple Errands Test-Hospital Version (MET-HV) in a real mall and in the VMall. RESULTS Participants achieved improvements ranging from 20.5% to 51.2% for most of the MET-HV measures performed in a real shopping mall and in the VMall. CONCLUSIONS The data support the VMall's potential as a motivating and effective intervention tool for the rehabilitation of people poststroke who have multitasking deficits during the performance of daily tasks. However, because the sample was small, additional intervention studies with the VMall should be conducted.
MANAGEMENT OF THE INFANT BORN TO A MOTHER INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1): CURRENT CONCEPTS

Despite the use of highly active antiretroviral therapy (HAART) and the success of protocol PACTG-076 in decreasing perinatal transmission of HIV infection in many industrialized countries, a total of 5,600,000 new cases of HIV infection were diagnosed worldwide in 1999. Of those cases, more than 10% are children under 15 years of age. The vast majority of pediatric HIV infection is due to perinatal transmission. More than 95% of HIV-infected people live in the developing world. Different studies are currently being conducted with modifications of the original PACTG-076, especially shorter courses of zidovudine (ZDV), combinations of antiretrovirals (ZDV and 3TC), or comparison of a modified version of the standard ZDV course vs. a single dose of nevirapine for the mother intrapartum and also for the newborn. The results of these studies may provide more affordable, alternative regimens to prevent maternal-to-child HIV-1 transmission for developing countries than the PACTG-076 protocol. It is very important that physicians and physician extenders (nurse practitioners and physician assistants) caring for infants born to HIV-infected mothers have an understanding of the pathophysiology of vertical HIV-1 infection transmission. They should be familiar with the conditions associated with an increased risk of transmission, interventions available to decrease this risk, current medications, and laboratory resources.
Family needs at a post-acute rehabilitation setting and suggestions for supports

Abstract Objective: To explore the perceived needs, obstacles to services, psychological distress and social problem-solving abilities of family members of persons with ABI at a post-acute community-based brain injury rehabilitation facility and offer suggestions for methods of assessment and providing support. Participants: Twenty-nine family members who did not provide daily care, but were involved in the care process. Design: Participants completed self-report questionnaires including the FNQ:R, SOS, DASS-21, WHO-QOL BREF and SPSI:R-S. Results: Participants reported informational and professional needs as most met and involvement in care, instrumental support and emotional support as most unmet. Most were satisfied with the amount of professional help and services and had confidence in the quality of care. Nearly half of the family members felt there were few ABI-related resources in the community and one third were unaware of good ABI treatment resources in their community. Psychosocial functioning was generally average. Conclusion: Family members who do not provide daily care are still impacted by the neurobehavioural changes that progress throughout the long-term, post-acute community phase. This study offers suggestions regarding an effective methodology for assessing family needs and recommends accessible and practical supports.
Absorption of ofloxacin isomers in the rat small intestine

Ofloxacin, a chiral fluoroquinolone, possesses two optical isomers. The antibacterial activity of S-(-)-ofloxacin is 8 to 128 times higher than that of R-(+)-ofloxacin. In the rat, a saturable absorption process has been described for racemic ofloxacin. In the present study we investigated the mechanism underlying the in vivo intestinal absorption of ofloxacin enantiomers in the rat. Blood samples were collected from the portal vein. Our results show that the intestinal absorption of ofloxacin isomers is pH dependent, both enantiomers being best absorbed at neutral pH. S-(-)-Ofloxacin seems to have a greater affinity for the intestinal transporter (initial concentrations at 5 min [C(init)] are 0.17 +/- 0.04 and 0.12 +/- 0.03 microg/ml for S-(-)- and R-(+)-ofloxacin, respectively). Dipeptides fail to modify ofloxacin absorption, but amino acids reduce both isomers' absorption (C(init) is reduced by 53 and 33% with glycine for S-(-)- and R-(+)-ofloxacin, respectively, and by 59 and 42% with L-leucine). Gamma amino butyric acid interferes with the absorption of ofloxacin isomers, but less seriously than do amino acids. Furthermore, ofloxacin competes with other fluoroquinolones or P-glycoprotein substrates for a common secretory pathway, resulting in an increased rate of absorption for both ofloxacin isomers; this is probably an indirect result of their reduced efflux from the apical side of intestinal cells.
Assessment of Nutritional Practices of Pregnant Mothers on Maternal Nutrition and Associated Factors in Guto Gida Woreda, East Wollega Zone, Ethiopia

Nutrition is a fundamental pillar of human life, health and development throughout the entire life span. The nutrition requirement varies with respect to age, gender and during physiological changes such as pregnancy. Pregnancy is a critical phase in a woman's life, when the expectant mother needs optimal nutrients of superior food qualities to support the developing fetus. The aim of this study was to assess the practices of pregnant mothers on maternal nutrition and associated factors in Guto Gida Woreda, East Wollega Zone, Ethiopia. The study was conducted during January to June of the year 2013, using quantitative cross-sectional descriptive study on a sample of 422 pregnant women and supplemented by qualitative study (focus group discussion). The quantitative data were analyzed using SPSS for windows version (16.0). Multiple logistic regression was run to assess factors that were associated with the dependent variable at P<0.05 and to control the confounders. Finally, the result of the study was presented using narratives and tables. This research showed only 33.9% of the respondents were found to have good nutritional practices during their pregnancy. There was a positive significant relation between information about nutrition and family size and nutritional practices of mothers during pregnancy (P<0.001). The practices of pregnant mothers about maternal nutrition were relatively low in this study. Information about nutrition and family size of mothers had a positive significant relation with mothers’ nutrition practices in the study area. Hence, the government in collaboration with concerned bodies should focus on nutritional education and information about nutrition to increase the practices of pregnant mothers on maternal nutrition during pregnancy in the study area.
Unified Digital Current Mode Control Tuning With Near Optimal Recovery in a CCM Buck Converter

Linear small-signal models of a dc-dc converter often ignore switching dynamics; thus such models are insufficient to fully explore the performance objective under large signal transients. Linear/nonlinear hybrid controllers are promising alternatives; however, they require structurally different hardware resources along with extra antiwindup arrangements. This paper proposes a geometric tuning method in a digitally current-mode-controlled buck converter under continuous-conduction mode. This considers a proportional-integral voltage controller along with a load current feedforward in the digital domain, while the inductor current has a traditional analog implementation. This resembles a first-order switching surface with near load-invariant regulation; thus a (fixed) small integral gain is sufficient to minimize the steady-state error. Using phase-plane geometry, the objective is to tune the controller gain in a way to achieve proximate time optimal recovery using a fixed-frequency pulse-width modulator and also to retain the large-signal stability. The effects of parameter variation and finite sampling are analyzed. The proposed tuning is implemented using an FPGA device.
Phosphatidylinositol 3-kinase- inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals

Targeted therapy with imatinib in chronic myeloid leukemia (CML) prompted a new treatment paradigm. Unlike CML, chronic lymphocytic leukemia (CLL) lacks an aberrant fusion protein kinase but instead displays increased phosphatidylinositol 3-kinase (PI3K) activity. To date, PI3K inhibitor development has been limited because of the requirement of this pathway for many essential cellular functions. Identification of the hematopoieticselective isoform PI3Kunlocks a new therapeutic potential for B-cell malignancies. Herein, we demonstrate that PI3K has increased enzymatic activity and that PI3Kis expressed in CLL cells. A PI3Kselective inhibitor CAL-101 promoted apoptosis in primary CLL cells ex vivo in a doseand time-dependent fashion that was independent of common prognostic markers. CAL-101–mediated cytotoxicity was caspase dependent and was not diminished by coculture on stromal cells. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell–activating factors CD40L, TNF, and fibronectin. In contrast to malignant cells, CAL-101 does not promote apoptosis in normal T cells or natural killer cells, nor does it diminish antibody-dependent cellular cytotoxicity. However, CAL-101 did decrease activated T-cell production of various inflammatory and antiapoptotic cytokines. Collectively, these studies provide rationale for the clinical development of CAL-101 as a first-in-class targeted therapy for CLL and related B-cell lymphoproliferative disorders. (Blood. 2010;116(12):2078-2088)
The effect of non‐uniform radiative damping on the zonal‐mean dynamics of the extratropical middle atmosphere

The effect of spatial and temporal variations in the radiative damping rate on the response to an imposed forcing or diabatic heating is examined in a zonal‐mean model of the middle atmosphere. Attention is restricted to the extratropics, where a linear approach is viable. It is found that regions with weak radiative damping rates are more sensitive in terms of temperature to the remote influence of the diabatic circulation. The delay in the response in such regions can mean that ‘downward’ control is not achieved on seasonal time‐scales. A seasonal variation in the radiative damping rate modulates the evolution of the response and leaves a transient‐like signature in the annual mean temperature field.
Discovery of microRNAs during early spermatogenesis in chicken

Spermatogenesis is a complex process that involves many elements. However, until now, little is known at the molecular level about spermatogenesis in poultry. Here we investigated microRNAs and their target genes that may be involved in germ cell development and spermatogonial in chicken. We used next-generation sequencing to analyze miRNA expression profiles in three types of germline cells: primordial germ cells (PGCs), spermatogonial stem cells (SSCs), and spermatogonia (Sp) during early stage of spermatogenesis. After validated the candidate miRNAs and corresponding genes’ expression in three types of cells, we found 15 miRNAs that were enriched 21 target genes that may be involved in spermatogenesis. Among the enriched miRNAs, miR-202-5p/3p were up-regulated in the Sp library and down-regulated in the PGCs library. Through RT-qPCR and Dual-Luciferase reporter assay, we confirmed that miR-202-5p bind to LIMK2 and involved in germ cell development. Collectively, we firstly discover the novel miRNAs, like miR-202-5p, and its related genes and pathways, expressed during the early spermatogonial stage in chicken, which will provide new clues for deciphering the molecular mechanism of the miRNAs regulating germline stem cell differentiation and spermatogenesis in chicken.
Emerging therapies for fibromyalgia: an update

Importance of the field: Fibromyalgia syndrome (FMS) is currently perceived by rheumatologists and pain physicians alike as representing the classic condition of central sensitization. This term has come to denote a condition in which chronic, widespread pain is attributed mainly to an increase in the processing and handling of pain by the CNS. Thus, effective treatment of the pain of FMS must be directed at the function of the CNS. Over recent years, the pharmacological industry has focused increasing attention on this syndrome, leading to the recent approval of three first medications specifically indicated in the treatment of FMS (i.e., pregabalin, duloxetine and milnacipran). Nonetheless, treatment of FMS remains challenging and in many cases incompletely successful. Issues with drug compliance and side effects, as well as limitations of intrinsic effectiveness, hamper the outcome in many cases. Thus, FMS continues to pose a significantly unmet medical need. Areas covered in this review: In the current review, we attempt to update readers on novel developments in the FMS over the last 2 years. We include a discussion of the various pharmacological classes of medications which appear to be of promising potential in this area, including sodium oxybate, dopamine agonists, naltrexone, novel anticonvulsive medications, synthetic cannabinoids, NMDA antagonists and others. What the reader will gain: Readers of this review will gain a glimpse into upcoming pharmacological directions in the management of FMS as well as attain an understanding of the mechanisms and pathophysiological pathways which are currently considered targets for drug development in FMS. Take home message: Following the introduction of three medications specifically indicated in the management of FMS over the last 4 years, additional research is actively leading towards the introduction of new drugs aimed at improving symptoms related to pain and sleep in FMS. Physicians involved in the treatment of FMS patients are required to keep up-to-date on these promising avenues of progress and to be ready to incorporate them into clinical use.
Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross‐talk with estrogen receptor

The molecular mechanisms by which ovarian hormones stimulate growth of breast tumors are unclear. It has been reported previously that estrogens activate the signal‐transducing Src/p21ras/Erk pathway in human breast cancer cells via an interaction of estrogen receptor (ER) with c‐Src. We now show that progestins stimulate human breast cancer T47D cell proliferation and induce a similar rapid and transient activation of the pathway which, surprisingly, is blocked not only by anti‐progestins but also by anti‐estrogens. In Cos‐7 cells transfected with the B isoform of progesterone receptor (PRB), progestin activation of the MAP kinase pathway depends on co‐transfection of ER. A transcriptionally inactive PRB mutant also activates the signaling pathway, demonstrating that this activity is independent of transcriptional effects. PRB does not interact with c‐Src but associates via the N‐terminal 168 amino acids with ER. This association is required for the signaling pathway activation by progestins. We propose that ER transmits to the Src/p21ras/Erk pathway signals received from the agonist‐activated PRB. These findings reveal a hitherto unrecognized cross‐talk between ovarian hormones which could be crucial for their growth‐promoting effects on cancer cells.
Class-Specific Nonlinear Projections Using Class-Specific Kernel Spaces

In this paper, we propose a new approach for nonlinear Class-specific Discriminant Analysis that exploits a class-specific kernel space definition. We show that the proposed method can considerably reduce the time and space complexities of the standard Class-specific Kernel Discriminant Analysis. Our analysis is verified by experiments illustrating the efficiency of the proposed class-specific kernel-based learning approach.
Designing a Generic and Evolvable Software Architecture for Service Oriented Computing

Service Oriented Architecture (SOA) is becoming the new paradigm for developing enterprise systems. We consider SOA to be concerned with highlevel design of software, which is commonly called software architecture. In this respect, SOA can be considered to be a new architectural style. This paper proposes an advanced software architecture for information systems. It was developed by systematically applying solid software engineering principles such as loose coupling,interface stabilityandasynchronous communication to contemporary n-tier architectures for information systems in Java Enterprise Edition. The resulting architecture is SOA-compliant, generic and demonstrates to a high extent architectural qualities such as evolvability.