Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting of DC-SIGN on Human Dendritic Cells by Minor Fimbriated Porphyromonas gingivalis Strains Elicits a Distinct Effector T Cell Response1

The oral mucosal pathogen Porphyromonas gingivalis expresses at least two adhesins: the 67-kDa mfa-1 (minor) fimbriae and the 41-kDa fimA (major) fimbriae. In periodontal disease, P. gingivalis associates in situ with dermal dendritic cells (DCs), many of which express DC-SIGN (DC-specific ICAM-3 grabbing nonintegrin; CD209). The cellular receptors present on DCs that are involved in the uptake of minor/major fimbriated P. gingivalis, along with the effector immune response induced, are presently unclear. In this study, stably transfected human DC-SIGN+/− Raji cell lines and monocyte-derived DCs (MoDCs) were pulsed with whole, live, wild-type Pg381 or isogenic major (DPG-3)-, minor (MFI)-, or double fimbriae (MFB)-deficient mutant P. gingivalis strains. The influence of blocking Abs, carbohydrates, full-length glycosylated HIV-1 gp120 envelope protein, and cytochalasin D on the uptake of strains and on the immune responses was determined in vitro. We show that the binding of minor fimbriated P. gingivalis strains to Raji cells and MoDCs is dependent on DC-SIGN, whereas the double fimbriae mutant strain does not bind. Binding to DC-SIGN on MoDCs is followed by the internalization of P. gingivalis into DC-SIGN-rich intracellular compartments, and MoDCs secrete low levels of inflammatory cytokines and remain relatively immature. Blocking DC-SIGN with HIV-1 gp120 prevents the uptake of minor fimbriated strains and deregulates the expression of inflammatory cytokines. Moreover, MoDCs promote a Th2 or Th1 effector response, depending on whether they are pulsed with minor or major fimbriated P. gingivalis strains, respectively, suggesting distinct immunomodulatory roles for the two adhesins of P. gingivalis.
Survey of nationally registered emergency medical services providers: pediatric education.

STUDY OBJECTIVE To survey emergency medical services (EMS) providers on a national level to determine and describe their perspective regarding their initial and continuing education (CE) needs in pediatrics. METHODS A 10-question survey was developed, pilot-tested, and sent to EMS providers as a part of their National Registry of Emergency Medical Technicians reregistration materials. RESULTS Surveys were completed by 18,218 EMS providers, a response rate of 67%. During a typical month, 60% of emergency medical technician-paramedics (EMT-Ps), 84% of EMT-intermediates (EMT-Is), and 87% of basic EMTs (EMT-Bs) care for 0 to 3 pediatric patients. CE was identified by all provider levels as the main source of their pediatric knowledge and skills. A state or national mandate for required CE in pediatrics was supported by 76% of surveyed providers. More than 70% of all providers responded they were comfortable to some degree with their own ability and their EMS system's ability when confronted with a critical pediatric call. Cost, availability, and travel distance were identified by all levels as the primary barriers to obtaining pediatric CE. All levels identified infants as the age of greatest concern if the provider was called to manage a critical case. CONCLUSION Surveyed practicing nationally registered EMS providers have infrequent contact with pediatric patients and have acquired most of their pediatric knowledge and skills from CE. In general, these providers are comfortable with their personal and their system's ability to care for children, but clearly support the need for required pediatric CE and identify the birth to 3-year age range as the priority for an educational focus. Cost, travel distance, and availability of pediatric CE are barriers that should be considered if pediatric CE is to be required of EMS providers.
Haemodynamic responses to exercise, ATP infusion and thigh compression in humans: insight into the role of muscle mechanisms on cardiovascular function

The muscle pump and muscle vasodilatory mechanims are thought to play important roles in increasing and maintaining muscle perfusion and cardiac output during exercise, but their actual contributions remain uncertain. To evaluate the role of the skeletal muscle pump and vasodilatation on cardiovascular function during exercise, we determined leg and systemic haemodynamic responses in healthy men during (1) incremental one‐legged knee‐extensor exercise, (2) step‐wise femoral artery ATP infusion at rest, (3) passive exercise (n= 10), (4) femoral vein or artery ATP infusion (n= 6), and (5) cyclic thigh compressions at rest and during passive and voluntary exercise (n= 7). Incremental exercise resulted in progressive increases in leg blood flow (ΔLBF 7.4 ± 0.7 l min−1), cardiac output ( 8.7 ± 0.7 l min−1), mean arterial pressure (ΔMAP 51 ± 5 mmHg), and leg and systemic oxygen delivery and . Arterial ATP infusion resulted in similar increases in , LBF, and systemic and leg oxygen delivery, but central venous pressure and muscle metabolism remained unchanged and MAP was reduced. In contrast, femoral vein ATP infusion did not alter LBF, or MAP. Passive exercise also increased blood flow (ΔLBF 0.7 ± 0.1 l min−1), yet the increase in muscle and systemic perfusion, unrelated to elevations in aerobic metabolism, accounted only for ∼5% of peak exercise hyperaemia. Likewise, thigh compressions alone or in combination with passive exercise increased blood flow (ΔLBF 0.5–0.7 l min−1) without altering , MAP or . These findings suggest that the skeletal muscle pump is not obligatory for sustaining venous return, central venous pressure, stroke volume and or maintaining muscle blood flow during one‐legged exercise in humans. Further, its contribution to muscle and systemic peak exercise hyperaemia appears to be minimal in comparison to the effects of muscle vasodilatation.
Life-table analysis of cyclosporin A treatment in psoriatic arthritis: comparison with other disease-modifying antirheumatic drugs.

OBJECTIVES The aim of this study was to determine the cumulative probability of taking CsA in comparison to other DMARDs, as well as the reason for discontinuation of each DMARD, in a large cohort of PsA patients. METHODS We prospectively studied 172 consecutive patients with a diagnosis of PsA who had been admitted to our rheumatological unit since 1984. We collected information about treatment with DMARDs including: number, dose, duration and causes of withdrawal, including side effects or inefficacy. Cumulative survival analysis was performed by the Kaplan-Meier test and the differences between these survival curves were determined by the Mantel-Hanszel test. RESULTS The probability curve of continuing to take CsA was significantly lower than that of MTX (p < 0.046). The rate of adverse effects responsible for stopping DMARD therapy was higher in the CsA group, especially with respect to the antimalarial group (p < 0.014). The most common cause of CsA withdrawal was hypertension. The rate of withdrawal due to inefficacy in the CsA group was not significantly different from those observed in the other groups. Nevertheless, the total frequency of discontinuation due to toxicity and inefficacy in the MTX group was significantly lower compared to the gold salts (p < 0.05) and CsA groups (p < 0.01). CONCLUSION Life-table analysis suggests that PsA patients taking CsA are less likely than patients on MTX to continue long term treatment. Therefore CsA, which seems to be less safe than the antimalarials, could be considered a useful drug in the treatment of PsA, but does seem to represent the drug of first choice, particularly when compared to MTX.
TÜKETİCİLER MARKALARI NASIL TERCİH EDİYOR? ( Kamu Sektörü Çalışanlarının Giysi Markalarını Tercihini Etkileyen Faktörlere Yönelik Bir Araştırma)

Gunumuzde isletmelerin yogun rekabet ortaminda rakiplerinden farklilasmasive tuketicinin zihninde yer almasimarkalasma ile mumkun olmaktadir. Marka, tuketicilerin ilgisini cekmek ve satin almaya tesvik etmek icin en onemli faktordur. Tuketicilerin satin alma davranislari urunun/hizmetin ozelliklerinin yaninda hedef kitlenin demografik, psikolojik, sosyolojik vb. ozellikleri tarafindan da etkilenmektedir. Tuketicilerin bircok marka arasindan birini tercih etmesi isletmenin hedef kitlesinin ozelliklerini belirlemesi ve buna uygun olarak stratejiler gelistirmesine baglidir. Hedef kitlesine mesajinidogru bir sekilde iletmesi yoluyla marka imajigelistirmek ve markaya baglilik yaratmak isletmelerin temel amacihaline gelmistir. Bu calismada, kamu sektorunde calisan tuketicilerin giysi satin alma davranislarinda marka tercihleri ve bunlari etkileyen faktorler degerlendirilmektedir.
Increased Transcription Levels Induce Higher Mutation Rates in a Hypermutating Cell Line1

Somatic hypermutation, in addition to V(D)J recombination, is the other major mechanism that generates the vast diversity of the Ab repertoire. Point mutations are introduced in the variable region of the Ig genes at a million-fold higher rate than in the rest of the genome. We have used a green fluorescent protein (GFP)-based reversion assay to determine the role of transcription in the mutation mechanism of the hypermutating cell line 18-81. A GFP transgene containing a premature stop codon is transcribed from the inducible tet-on operon. Using the inducible promoter enables us to study the mutability of the GFP transgene at different transcription levels. By analyzing stable transfectants of a hypermutating cell line with flow cytometry, the mutation rate at the premature stop codon can be measured by the appearance of GFP-positive revertant cells. Here we show that the mutation rate of the GFP transgene correlates with its transcription level. Increased transcription levels of the GFP transgene caused an increased point mutation rate at the premature stop codon. Treating a hypermutating transfection clone with trichostatin A, a specific inhibitor of histone deacetylase, caused an additional 2-fold increase in the mutation rate. Finally, using Northern blot analysis we show that the activation-induced cytidine deaminase, an essential trans-factor for the in vivo hypermutation mechanism, is transcribed in the hypermutating cell line 18-81.
Collaboration through cartoons: drawing cartoons to assist collaborative ethnography with young children

Representing participants’ perspectives faithfully is a fundamental principle for collaborative ethnography (Lassiter 2005). Collaboration is difficult to achieve, however, when the participants are young children who do not share a language with the researcher. This article presents an innovative methodological approach that was employed during a twelve month, ESRC funded research project that aimed to explore the communicative practices of young children in a super-diverse, early years educational environment. In addition to writing field notes, the researcher sketched cartoon strips of the events being observed and shared these with the children. The paper describes how the cartoons facilitated a more collaborative approach to ethnographic research as the children became engaged in their creation and interpretation. The findings suggest that cartoons provide an accessible medium that opens up spaces for developing dialogue around the research process. This has important implications for any research that endeavours to listen to the participants’ perspectives, but particularly where the participants are young children or in cases where the researcher does not speak the languages of the participants fluently
Incidence, complications, and management of Meckel's diverticulum.

OBJECTIVES To elucidate the incidence of Meckel's diverticulum; to determine the correlation between the histologic type of the diverticulum's mucosa and its clinical presentation; and to review our experience with Meckel's diverticulum. DESIGN Case-control study. SETTING University hospital in Ioannina, Greece. PATIENTS A total of 2074 patients undergoing an appendectomy were examined intraoperatively for Meckel's diverticulum (subgroup A1). In addition, Meckel's diverticulum was found incidentally in 15 patients who were undergoing intra-abdominal surgery (subgroup A2). An operation for a complicated Meckel diverticulum was performed in an additional 15 patients (group B). RESULTS Thirty-three (1.59%) Meckel diverticulae were found incidentally among 2074 patients in subgroup A1. A positive correlation between Meckel's diverticulum and male sex was found (P < .004), but no difference was found in sex distribution between patients in group B and subgroup A1 (P < .6744). The histologic type of the mucosa (gastric) had significant positive correlation with the clinical presentation of the diverticulum (complicated) (P < .001). CONCLUSION Resection of the unexpected Meckel diverticulum can be performed safely with a low complication rate, regardless of the patient's age.
POSTNATAL DIFFERENTIATION AND REGIONAL HISTOLOGICAL VARIATIONS IN THE DUCTUS EPIDIDYMIDIS OF RAMS

The caput, corpus and cauda regions of the ductus epididymidis consisted of six histological segments that showed regional variations. The postnatal differentiation of the different segments started from birth and progressed till maturity. The simple epithelium at birth gained progressive pseudostratification. Similarly, the appearance of stereocilia, different types of cells in the epithelium and the smooth muscle layers around the epididymal tubules progressed and at different periods of postnatal development, the typical adult characteristics were achieved. The diameter of the epididymal tubules also increased, as age advanced. The developmental progression was disto-proximal i.e., the postnatal differentiation started in the terminal segment and then ascended through the middle and initial segments. The progression in the increase in height of the epithelium was varied in the three regions, whereas the progression in the increase in the diameter of epididymal tubules was uniform.
Depression and Psychological Well-being in Old Age

The main purpose of this research was to find out the mean difference between adult and aged in depression and psychological well being. The total 60 sample were taken out which 30 were adult (20 to 59 years) male and female and 30 were aged (60 years and above) male and female. The research tool for depression, Beck depression inventory was used. Here Guajarati adaption used. For psychological well being, Sudha Bhogle’s Psychological well being scale was used, translated in Gujarati and the t-test was applied to check the difference of depression and psychological well being and the Karl-person ‘r’ method used to check the correlation. Result reveals that significant difference in depression and psychological well being with respect to both adult and aged. While co-relation between depression and psychological well-being reveals -0.70 negative correlation.
Exposure‐time‐varying hazard function ratios in case‐control studies of drug effects

For many adverse effects of drugs, the instantaneous risk of an incident event per day of therapy (i.e., the hazard function) varies by duration of therapy and by prior exposure. In cohort studies of adverse drug effects time‐varying hazard functions are easily modeled using standard statistical software packages. Tests of the hypothesis of a constant proportional hazard function ratio are also available. In case control studies, the need to consider time‐varying hazard functions seems to be somewhat less well‐recognized than in cohort studies. When the hazard function ratio for an adverse drug event is not constant over time, an overall single odds ratio (OR) estimated in a case control study not accounting for the time variation in the hazard function is a weighted average of duration‐specific ORs with weights reflecting the distribution of exposure time in the study population. The resulting estimate depends not only on the drug but also on the exposure time distribution in the study population. This can lead to misleading conclusions when comparing the risks of two drugs within the same population and when comparing risks of the same drug in different populations. Analytic approaches for addressing time‐varying hazard functions in case‐control studies have been published but seem to be less used than in cohort studies. This article discusses adverse drug effects with time‐varying hazard functions and methods for addressing these in case‐control studies during study design, data collection, and analysis. Copyright © 2005 John Wiley & Sons, Ltd.
Focusing on Children's Inhalation Dosimetry and Health Effects for Risk Assessment: An Introduction

Substantial effort has been invested in improving children's health risk assessment in recent years. However, the body of scientific evidence in support of children's health assessment is constantly advancing, indicating the need for continual updating of risk assessment methods. Children's inhalation dosimetry and child-specific adverse health effects are of particular concern for risk assessment. When focusing on this topic within children's health, key issues for consideration include (1) epidemiological evidence of adverse effects following children's exposure to air pollution, (2) ontogeny of the lungs and effects on dosimetry, (3) estimation and variability of children's inhalation rates, and (4) current risk assessment methodologies for addressing children. In this article, existing and emerging information relating to these key issues are introduced and discussed in an effort to better understand children's inhalation dosimetry and adverse health effects for risk assessment. While much useful evidence is currently available, additional research and methods are warranted for improved children's health risk assessment.
Influence of different types of automated devices on the shaping ability of rotary nickel-titanium FlexMaster instruments.

AIM To compare the shaping ability of rotary FlexMaster nickel-titanium instruments in simulated curved canals and in curved canals of extracted teeth when set into permanent rotation with three different torque-limited automated devices. METHODOLOGY Root canal instrumentation was performed with three different torque-limited automated devices (ENDOadvance, SIRONiTi and Endo IT motor) by FlexMaster nickel-titanium instruments up to size 35. Simulated canals: 28 degree and 35 degree curved canals in resin blocks (n = 20 canals in each group) were prepared. Pre- and post-instrumentation images were recorded and assessment of canal shape was completed with a computer image analysis program. Extracted teeth: A total of 60 curved root canals were divided into three groups, which were balanced with respect to the angle and the radius of canal curvature. Straightening of the canal curvatures was determined with a computer image analysis program. Incidence of canal aberrations, preparation time, changes of working length and instrument failures were recorded both in simulated and real canals. RESULTS In simulated and real canals, instrumentation with Endo IT was significantly faster than with SIRONiTi (P < 0.05). With respect to canal aberrations in simulated canals, there were no significant differences between the devices (P > 0.05), even though more aberrations were created with ENDOadvance and SIRONiTi. In real canals, the Endo IT motor resulted in significantly less straightening during instrumentation (P < 0.05) than SIRONiTi. A total of three instruments separated (one file in each group) during the enlargement of 35 degree curved simulated canals. All systems maintained working distance well. CONCLUSIONS All systems respected original root canal curvature well and were safe, indicating that torque-limited rotation handpieces are suitable for preparing curved root canals.
Absorption of Different Doses of Fat Soluble and Water Miscible Preparations of Vitamin E in Children with Cystic Fibrosis

A comparison of the intestinal absorption of water miscible and fat soluble preparations of α-tocopheryl acetate in children with cystic fibrosis showed the water miscible preparation to be more efficiently absorbed. In the absence of liver disease, a daily dose of 1 mg/kg body weight of a water miscible preparation can be expected to correct any pre-existing vitamin E deficiency within 2 months of starting treatment, and is adequate for subsequent maintenance.
Challenges and opportunities for new protein crystallization strategies in structure-based drug design

Structure-based drug design (SBDD) has emerged as a valuable pharmaceutical lead discovery tool, showing potential for accelerating the discovery process, while reducing developmental costs and boosting potencies of the drug that is ultimately selected. SBDD is an iterative, rational, lead compound sculpting process that involves both the synthesis of new derivatives and the evaluation of their binding to the target structure either through computational docking or elucidation of the target structure as a complex with the lead compound. This method heavily relies on the production of high-resolution (< 2 Å) 3D structures of the drug target, obtained through X-ray crystallographic analysis, in the presence or absence of the drug candidate. The lack of generalized methods for high quality crystal production is still a major bottleneck in the process of macromolecular crystallization. This review provides a brief introduction to SBDD and describes several macromolecular crystallization strategies, with an emphasis on advances and challenges facing researchers in the field today. Recent trends in the development of more universal macromolecular crystallization techniques, particularly nucleation-based techniques that are applicable to both soluble and integral membrane proteins, are also discussed.
Plaques on the Wall: Inducing Anticonvulsant Use and Atherogenesis

Commentary Ascertaining the adverse effects (AEs) of a antiepileptic drug (AED) can be a very tricky business. It seems like it should be easy: just give it to a bunch of people and see what happens. That works for some AEs, but for others it can be quite problematic. For example, some AEs are vague and hard to define (e.g., fatigue), and some can be confounded by their relationship to the underlying disease (e.g., cognitive impairment, depressed mood). The clearest way to establish causation is with a randomized trial, which can sometimes address these issues. But there are other side effects that are relatively rare (e.g., aplastic anemia) or that only occur over a protracted period of time (e.g., osteoporosis). For these latter types of AEs, no randomized trial could be large enough or long enough to establish causation, thereby requiring Plan B. Plan B can take a number of different forms. In the case of very rare and serious side effects, surveillance of spontaneous reporting systems is often utilized; for example, this was enough to establish the life-threatening effects of felbamate (1). Of course, spontaneous reports will only occur for very dangerous or unusual occurrences, so this isn’t suitable for more mundane or common AEs. Another possibility is simply to do a large epidemiologic study of a database to ascertain whether the AE in question occurs more frequently in patients treated with a given drug than in patients not treated with that drug. This may seem like the most straightforward approach, but it is actually greatly complicated by a number of issues, including the appropriate choice of control group, inherent differences in populations, differential prescribing habits, and data limitations in large databases. These concerns make performing such studies deceptively difficult, though it has been done to ascertain the incidence of fractures with enzymeEffects of Long-Term Antiepileptic Drug Monotherapy on Vascular Risk Factors and Atherosclerosis.