Miracle-dz/UniFAR-FTUs huggingface dataset:
Diazinon toxicokinetics, tissue distribution and anticholinesterase activity in the rat.

The toxicokinetics, tissue distribution, and anticholinesterase (antiChE) activity of diazinon were investigated in the rat. Plasma concentrations most adequately fitted a two-compartment open model after i.v. administration of 10 mg/kg and a one-compartment model after oral administration of 80 mg/kg. Diazinon elimination half-life following i.v. and oral dosing was 4.70 and 2.86 h, respectively. The oral bioavailability was found to be low (35.5%). Hepatic extraction ratios after i.v. administration of 5 or 10 mg/kg were 54.8% and 47.7%, respectively, suggesting that low systemic oral bioavailability can be explained by a first-pass effect in the liver. Diazinon was found to be approximately 89% protein-bound in plasma within the concentration range 0.4-30 ppm. The highest concentration of diazinon after i.v. administration was found in the kidneys, when comparing to liver, kidney, brain. Both red blood cell (RBC) acetylcholinesterase (AChE) and plasma ChE activities were inhibited rapidly (44% and 17% at 10 min, and 36% and 13% min for i.v. and oral administration, respectively), but inhibition of RBC AChE was greater than that of plasma ChE.
Brain Natriuretic Peptide and C‐Type Natriuretic Peptide Maintain Porcine Oocyte Meiotic Arrest

Recent studies have shown that C‐type natriuretic peptide (CNP) serves as a key control system during mouse oocyte maturation. We used pig models (in vitro and in vivo) to explore the role played by the natriuretic peptide family in porcine oocyte maturation. We reported the expression and location of natriuretic peptide system in different stages of porcine antral follicles. Atrial natriuretic peptide (ANP) and CNP were expressed primarily in granulosa cells, whereas brain natriuretic peptide (BNP) and natriuretic peptide receptor‐B (NPRB) receptor were expressed in granulosa cells (both cumulus and mural granulosa cells) and thecal internal cells, and the natriuretic peptide receptor‐A (NPRA) receptor predominantly in thecal cells. Upon in vitro culture, BNP and CNP maintained meiotic arrest of oocytes associated with cumulus cells. The expression levels of BNP, CNP, and the NPRB receptor increased upon treatment of prepubertal gilts with pregnant mare's serum gonadotropin and decreased upon subsequent human chorionic gonadotropin injection. Such dynamic changes in the expression of natriuretic peptides and their receptor paralleled the proportions of oocytes exhibiting nuclear maturation in vivo. These data indicated that BNP and CNP co‐contributed to maintaining porcine meiotic arrest under physiological condition and lutenizing hormone (LH) relieved this inhibitory effect by decreasing the expression levels of BNP and CNP in vivo. Our present work, combined with previous data, improved the understanding of the oocyte meiotic arrest mechanisms and further revealed that natriuretic peptides serve as oocyte maturation inhibitor (OMI) to inhibit oocyte maturation in mammals. J. Cell. Physiol. 230: 71–81, 2015. © 2014 Wiley Periodicals, Inc.
Outcome of out-of-hospital cardiac or respiratory arrest in children.

BACKGROUND Among adults who have a cardiac arrest outside the hospital, the survival rate is known to be poor. However, less information is available on out-of-hospital cardiac arrest among children. This study was performed to determine the survival rate among children after out-of-hospital cardiac arrest and to identify predictors of survival. METHODS We reviewed the records of 101 children (median age, two years) with apnea or no palpable pulse (or both) who presented to the emergency department at the Hospital for Sick Children in Toronto. The characteristics of the patients and the outcomes of illness were analyzed. We assessed the functional outcome of the survivors using the Pediatric Cerebral and Overall Performance Category scores. RESULTS Overall, there was a return of vital signs in 64 of the 101 patients; 15 survived to discharge from the hospital, and 13 were alive 12 months after discharge. Factors that predicted survival to hospital discharge included a short interval between the arrest and arrival at the hospital, a palpable pulse on presentation, a short duration of resuscitation in the emergency department, and the administration of fewer doses of epinephrine in the emergency department. No patients who required more than two doses of epinephrine or resuscitation for longer than 20 minutes in the emergency department survived to hospital discharge. The survivors who were neurologically normal after arrest had had a respiratory arrest only and were resuscitated within five minutes after arrival in the emergency department. Of the 80 patients who had had a cardiac arrest, only 6 survived to hospital discharge, and all had neurologic sequelae. CONCLUSIONS These results suggest that out-of-hospital cardiac arrest among children has a very poor prognosis, especially when efforts at resuscitation continue for longer than 20 minutes and require more than two doses of epinephrine.
The Use of CRP Tests in Patients with Respiratory Tract Infections in Primary Care in Sweden Can Be Questioned

A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1 week in November in 2000 and 2002 respectively. As a part of the study, the use and results of C-reactive protein (CRP) tests in relation to duration of symptoms and antibiotic prescribing in 6778 patients assigned a diagnosis of respiratory tract infections were analysed. In almost half (42%) of the patients, a CRP test was performed. The majority of CRP tests (69%) were performed in patients assigned diagnosis upper respiratory tract infection, where the test is not recommended. Overall, there was a minor decrease in antibiotic prescribing when CRP was used (41%), in comparison to 44% of the patients where no CRP was performed (p<0.01). Patients assigned diagnoses implying a bacterial aetiology were prescribed antibiotics irrespective of result of CRP or length of symptoms before consultation. For patients assigned viral diagnoses, antibiotic prescribing increased with increasing duration of symptoms and increasing value of CRP. The use of CRP decreased antibiotic prescribing in patients assigned to viral diagnoses and with longstanding symptoms (p<0.001). However, 59% of the patients assigned viral diagnoses with CRP≥25 received antibiotics, which seems to indicate a misinterpretation of CRP and a non-optimal use of antibiotics.
Association between bariatric surgery and rate of hospitalisations for stable angina pectoris in obese adults

Objective Obesity and stable angina pectoris (SAP) are important public health problems in the USA. However, little is known about whether weight reduction affects the rate of SAP-related morbidities. This study was designed to test the hypothesis that bariatric surgery is associated with a lower rate of hospitalisations for SAP in obese adults. Methods We performed a self-controlled case series study of obese adults with SAP who underwent bariatric surgery using a population-based inpatient database in three states (California, Florida and Nebraska) from 2005 to 2011. The primary outcome was hospitalisation for SAP. We used conditional logistic regression to compare the rate of the outcome event during sequential 12-month periods, using presurgery months 13–24 as a reference period. Results Our sample consisted of 953 patients with SAP who underwent bariatric surgery. The median age was 57 years, 51% were women, and 78% were non-Hispanic white. During the reference period, 25.3% (95%CI, 22.5% to 28.1%) had a hospitalisation for SAP. The rate remained stable in the subsequent 12-month presurgery period (adjusted OR (aOR) 0.84 (95% CI, 0.69 to 1.02); p=0.07). In the first 12-month period after bariatric surgery, we observed a significantly lower rate (9.1% (95% CI, 7.3% to 11.0%); aOR 0.33 (95% CI, 0.26 to 0.43); p<0.0001). Similarly, the rate remained significantly lower in the subsequent 13–24 months after bariatric surgery (8.7% (95% CI, 6.9% to 10.5%); aOR 0.31 (95% CI, 0.24 to 0.41); p<0.0001). Conclusion In this population-based study of obese adults with SAP, we found that the rate of hospitalisations for SAP was lower by two-thirds after bariatric surgery.
Relation of haemofilter type to venous catheter resistance is crucial for filtration performance and haemocompatibility in CVVH--an in vitro study.

BACKGROUND Main factors for the overall performance of haemofilters (HF) are membrane features and filter durability without clogging/clotting of capillaries. However, the venous line resistance (Pv) is a powerful force for net filtrate flux resulting in haemoconcentration and thus is enhancing the phenomenon of membrane clogging. Therefore, we hypothesized that catheter type, as it is associated with Pv-levels, contributes to the extent in which filter longevity and filtration performance are restricted due to blocked hollow fibres. METHODS Heparinized porcine blood (5 IU/ml) was circulated in an in vitro system for haemofiltration (FH6S-filters were used, Ca. Gambro). Three different sizes of catheters for peripheral vein access (Vygonuele V, Ca. Vygon) were alternately inserted into the circuit for blood return from the filter to the reservoir. To produce Pv-levels lower than commonly induced by Shaldon catheters, a 14G-vygonuele was used. Pv-levels standard for 11-12 French catheters were provided by using a 16G-vygonuele. To produce Pv-levels common for low-French or tri-lumen catheters, a shortened 18G-vygonuele was used. The respective Pv-levels attained were compared with respect to the overall filtration performance (system pressures, haemocompatibility and sieving coefficients). RESULTS Catheters of 14 and 16G enabled transiently maximal blood flow (Qb)/filtration rates (Qf) of 300/60 ml/min and continuous filtration with Qb/Qf of 200/40 ml/min. The shortened 18G catheter reduced maximal flow rates down to Qb/Qf of 200/40 ml/min, and continuous flow rates down to Qb/Qf of 125/25 ml/min. At the end, median values for blocked hollow fibres were, 35% in the 14G-group, 40% in the 18G-group and 70% in the 16G-group. Haemocompatibility appeared to be higher in the 14G-group with respect to various parameters when compared with the other groups. CONCLUSIONS The flow resistance by the catheter chosen for haemofiltration clearly influenced the filtration performance. Thus, investigations focused on compatibility of catheter type as it related to Pv-levels with the particular method of renal replacement therapy that should be performed. This point could be crucial in reducing filter clogging and haemostasis during CVVH.
Effects of Cueing and Knowledge of Results on Workload and Boredom in Sustained Attention

Two models of recently reported high workload associated with vigilance tasks are the direct-cost and indirect-cost views. The former attributes high workload to the need for continuous observation in discriminating signals from neutral events; the latter attributes it to efforts to combat the boredom associated with monotonous vigilance tasks. These opposing views were tested by providing observers with reliable cueing, which rendered observation necessary only when low-probability critical signals were imminent, or with knowledge of results (KR) regarding performance efficiency. On the basis of cue and KR differences in elicited observation activity and motivational value, the direct-cost model led to the anticipation that cueing would result in a high-boredom, low-workload profile and a greater reduction in workload than KR. The indirect-cost model led to the prediction that cueing would result in a high-boredom, high-workload profile and a lesser reduction in workload than KR. The results clearly supported the direct-cost view that the workload of vigilance is task-induced. Consequently, efforts to combat high workload in complex automated systems requiring substantial monitoring by operators should focus specifically upon task-related determinants.
Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice

Mice (C57BL/6), treated with progesterone and infected intravaginally with the mouse pneumonitis strain of Chlamydia trachomatis (MoPn), acquired genital tract disease that ascended from the endocervix to the uterine horns, oviducts, and ovaries in a temporal fashion before the occurrence of spontaneous microbiological resolution by about 28 days after infection. Surprisingly, dissemination of MoPn in small numbers to draining lymph nodes, the peritoneal cavity, spleen, liver, kidneys, and lungs occurred in normal mice during the early stages of disease (7 to 14 days) in a portion of infected animals but resolved from these tissues, by microbiological criteria, prior to resolution of genital tract involvement. In contrast, gamma interferon knockout (IFN-gamma KO) mice exhibited dissemination of infection to a greater extent and for longer periods in a variety of tissues, and a portion of infected IFN-gamma KO mice failed to microbiologically resolve their genital tract disease. By comparison, C57BL/6 SCID mice uniformly failed to resolve their genital tract disease and exhibited high levels of dissemination to all tissues tested for extended (50-day) periods of times. Interestingly, although IFN-gamma KO mice failed to completely clear organisms from their genital tracts, they exhibited an attenuated infection indistinguishable from that of heterozygous littermates when challenged 112 days after primary infection. These data support a role for IFN-gamma in containing dissemination of MoPn from the genital tract to extragenital sites and in the microbiological resolution of infection. Data also indicate that IFN-gamma is not required for modulating reinfections, which normally follow a shorter and less dramatic course.
Trend and Factors Associated With Healthcare Use and Costs in Type 2 Diabetes Mellitus: A Decade Experience of a Universal Health Insurance Program

Background:Little is known about how a universal National Health Insurance program with cost-containment strategies affect costs and quality of diabetes care. Objectives:To examine the trends of healthcare use and costs for patients with type 2 diabetes mellitus (T2DM) in Taiwan over the last decade, and to identify factors associated with high healthcare cost and poor diabetes care. Research Design:We delineated the pattern of healthcare use and costs for T2DM in 2000–2010. Generalized linear and logistic regression models were used to identify factors associated with medical costs and diabetes care. Subjects:Representative adult T2DM patients and age-matched and sex-matched nondiabetes individuals were selected from the 2000, 2005, and 2010 National Health Insurance Research Databases. Measures:Healthcare use included physician visits, hospital admissions, and antidiabetic drug prescriptions. Indicators of diabetes management included completeness of recommended diabetes tests and medication adherence, assessed using medication possession ratio. Results:The total healthcare cost per diabetes patient was approximately 2.8-fold higher than that for nondiabetes individual. The growth of healthcare cost per diabetes patient was significantly contained by about 3694 New Taiwan dollars (3.6%) between 2005 and 2010, but diabetes care improved over the decade. Diabetes duration, income, place of residence, continuity of care, and enrollment to a pay-for-performance program were associated with healthcare costs and diabetes management. Some public health measures implemented to support diabetes care were also discussed. Conclusions:Healthcare costs could be controlled without sacrificing the quality of diabetes care by implementing pay-for-performance programs and effective health policies favorable for diabetes care.
Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy

The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti‐aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high altitude or cold regions of the world, has been reported to have anti‐aging effects in Drosophila. We demonstrated that a R. rosea extract and one of its bioactive components, salidroside, inhibited the growth of bladder cancer cell lines with a minimal effect on nonmalignant bladder epithelial cells TEU‐2. Interestingly, the R. rosea extract and salidroside component exhibited a selective ability to inhibit the growth of p53 knockout primary mouse embryo fibroblasts (p53−/− MEFs) compared to their wild‐type counterparts. The growth inhibitory effects of the R. rosea extract and salidroside were, however, attenuated in TSC2 and p53 double knock MEFs (TSC2−/−, p53−/− MEFs), suggesting that TSC2 protein is, at least in part, required for the growth inhibitory effects of the R. rosea extract and salidroside. The R. rosea extract and salidroside treatment of UMUC3 cells resulted in an increase of AMP‐activated protein kinase (AMPK)‐α phosphorylation and a decrease of 4E‐BP1 phosphorylation, leading to increased binding of 4E‐BP1 to m7 GTP. These results indicate that the R. rosea extract and salidroside inhibit translation initiation. Furthermore, both the R. rosea extract and salidroside treatment of UMUC3 cells caused a significant percentage of cells undergoing autophagy. Therefore, the R. rosea extract and salidroside deserve further study as novel agents for chemoprevention of bladder carcinogenesis. © 2011 Wiley Periodicals, Inc.
A practical guide to topical therapy in children

The parents of children with skin disease are often unsure how much topical therapy, particularly of corticosteroids, they should apply. The aims of this study were to devise simple guidelines on topical therapy for children, parents, doctors and nurses, and to check the accuracy of these guidelines in practice. The guidelines are based upon four principles: the adult fingertip unit (FTU); the ‘rule of 9s’; standard height and weight charts for children; and standard nomograms for calculating body surface area. Twenty‐four children (11 boys and 13 girls) aged 6 months to 9 years 4 months with atopic eczema were recruited and the number of FTUs required to treat different anatomical areas calculated in accordance with the proposed guidelines. Ointment was applied and the number of FTUs needed for each area was recorded. The amount used was then compared with that predicted. No child required a greater number of FTUs than that predicted, and the number of FTUs predicted for each anatomical region was accurate to within 1 FTU. The guidelines provide a useful indication of how much topical therapy is required for children, and advice sheets have been prepared for children of different ages.
Analysing the Similarity of Proteins Based on a New Approach to Empirical Mode Decomposition

The function of a protein can be partially determined by the information contained in its amino acid sequence. It can be assumed that proteins with similar amino acid sequences normally have closer functions. Hence analysing the similarity of proteins has become one of the most important areas of protein study. In this work, a layered comparison method is used to analyze the similarity of proteins. It is based on the empirical mode decomposition (EMD) method, and protein sequences are characterized by the intrinsic mode functions (IMFs). The similarity of proteins is studied with a new cross-correlation formula. It seems that the EMD method can be used to detect the functional relationship of two proteins. This kind of similarity method is a complement of traditional sequence similarity approaches which focus on the alignment of amino acids.
Incidence of New-onset and Flare of Preexisting Psoriasis During Rituximab Therapy for Rheumatoid Arthritis: Data from the French AIR Registry

Objective. Psoriasis could be a paradoxical reaction to tumor necrosis factor-α antagonist therapy and it has been reported with rituximab therapy. Our objective was to assess the rates of new-onset and flare of preexisting psoriasis in patients taking rituximab for rheumatoid arthritis (RA). Methods. The nationwide multicenter prospective AutoImmunity and Rituximab (AIR) registry was set up in 2006 by the French Society for Rheumatology to collect data on patients taking rituximab for joint diseases. We identified patients with RA in the registry who had psoriasis listed as an adverse drug reaction, and we obtained additional information from their physicians if needed. We computed the incidence rates of new-onset and flare of preexisting psoriasis according to the rituximab exposure time. Results. Among the 1927 patients in the registry with RA, 2 had new-onset and 5 had flare of preexisting psoriasis after a median followup of 39.2 weeks. Incidence rates were 1.04/1000 person-years (95% CI 0.13 to 3.8) for new-onset psoriasis and 2.6/1000 person-years (95% CI 0.84 to 6.1) for flare of preexisting psoriasis. Rituximab rechallenge in the 2 new-onset cases and in 2 flare cases was not followed by recurrence or exacerbation of psoriasis. Two of the 5 flare cases developed after discontinuation of methotrexate. Conclusion. Despite the small number of cases observed, leading to wide CI, the incidence rates in our study do not support a causative role of rituximab therapy in new-onset or flare of preexisting psoriasis in patients with RA.
Streptococcus pyogenes biofilm growth in vitro and in vivo and its role in colonization, virulence, and genetic exchange.

BACKGROUND Group A streptococcus (GAS) commonly colonizes the oropharynx and nonintact skin. However, colonization has been little studied and the role of biofilm formation is unclear, as biofilm experiments to date have not been conducted under conditions that mimic the host environment. METHODS In this study we grew GAS biofilms on human keratinocytes under various environmental conditions and used this model to evaluate colonization, invasive disease and natural transformation. RESULTS GAS grown on epithelial cells, but not biofilms grown on abiotic surfaces, produced biofilms with characteristics similar to in vivo colonization. These biofilm bacteria showed a 100-fold higher bacterial burden of nasal-associated lymphoid tissue in mice than broth-grown bacteria, and were not virulent during septic infection, which was attributed in part to down-regulation of genes typically involved in localized and invasive disease. We also showed for the first time that GAS were naturally transformable when grown in biofilms and during colonization of NALT in vivo. CONCLUSIONS These findings provide novel model systems to study biofilm formation of GAS in vitro and in vivo, suggest an important role for biofilm formation during GAS colonization, and provide an explanation for the known genome diversity within the GAS population.