Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced sulfated‐proteoglycan core protein synthesis by incubation of rabbit chondrocytes with recombinant transforming growth factor‐β1

Rabbit articular chondrocytes were incubated with recombinant transforming‐growth‐factor‐β 1, (rhTGF‐β1) and its effect on newly synthesized proteoglycan measured. rhTGF‐β1 stimulated proteoglycan synthesis at a concentration as low as 5 ng/ml without further increase in radiosulfate incorporation up to 50 ng/ml. The quantitative increase in radiosulfate incorporation in rh‐TGF‐β1‐treated chondrocytes was greater in the cell‐associated culture compartment than in the medium compartment. rhTGF‐β1 promoted an increased proteoglycan retention in the cell‐associated compartment as evidenced by an increase in the t 1/2 retention from 8 h to 11 h. Specific enhanced synthesis of [35S]‐methionine‐labeled core proteins was seen in rh‐TGF‐β1‐treated chondrocytes. rh‐TGF‐β1 increased the synthesis of the 2 core proteins derived from hydrodynamically large proteoglycans. They possessed apparent molecular weights of > 480 kD and 390 kD after 3‐5% acrylamide gel electrophoresis. A compartmental analysis revealed that the cell‐associated culture compartment contained only the larger of the 2 core proteins derived from large proteoglycans. Two other core proteins with apparent molecular weights 52 kD and 46 kD were also stimulated by rhTGF‐β1. These results indicated that TGF‐β probably plays a significant role in stimulating proteoglycan core protein synthesis in articular chondrocytes and therefore may be an important growth factor in the restoration of cartilage extracellular matrix after injury.
Section 3, Component 2: Education for a Partnership in Asthma Care

♦ Observational studies and limited clinical trials support consideration of focused, targeted patient education in the ED setting (e.g., teaching inhaler technique and providing an ED asthma discharge plan with instructions for discharge medications and for increasing medication or seeking medical care if asthma should worsen). Studies demonstrate the benefits of education in the hospital setting (Evidence B).
Distinct N-Methyl—aspartate Receptor 2B Subunit Gene Sequences Confer Neural and Developmental Specific Expression*

Expression of the N-methyl—aspartate (NMDA) receptor 2B (NR2B) subunit is neural-specific and differentially regulated. It is expressed in the forebrain and in cerebellar granule cells at early postnatal stages and selectively repressed in the cerebellum after the second postnatal week, where it is replaced by the NR2C subunit. This switch confers distinct properties to the receptor. In order to understand the molecular mechanisms that differentially regulate the NR2B gene in the forebrain and cerebellum during development, we have isolated and characterized the promoter region of the NR2B gene. Two 5′ noncoding exons and multiple transcription start sites were identified. Transcriptional analysis in transgenic mice reveals that an upstream 800-base pair region, which includes the first exon, is sufficient to direct neural-specific transcription. Developmental repression of the gene in the cerebellum requires additional regulatory elements residing in the first intron or second exon. Sequence elements that may participate in the regulation of the NR2B gene were identified by comparison to other neural genes. These studies provide insight into the molecular mechanisms regulating the switch of NMDA receptor subunit expression in the cerebellum, which ultimately account for the physiological changes in receptor function during development.
Can the concept of hormesis Be generalized to carcinogenesis?

The concept of hormesis (i.e., low-dose stimulation/high-dose inhibition) has been shown to be widely generalizable with respect to chemical class, animal model, gender, and biological end point. The public health implication of this lack of linearity in the low-dose area of the dose-response curve raises the question of whether low doses of carcinogens will reduce cancer risk. Articles relating to the process of carcinogenesis (i.e., initiation, promotion, tumor development, and progression) were obtained from a recently developed chemical hormesis database and evaluated for their evidence of hormesis. Numerous examples in well-designed studies indicate that U- or J-shaped dose-response relationships exist with respect to various biomarkers of carcinogenesis in different animal models of both sexes. Examples of such J-shaped dose-response relationships in each stage of the process of carcinogenesis were selected for detailed toxicological examination. These results have important implications for both the hazard assessment of carcinogens and cancer risk assessment procedures.
An evaluation of patient satisfaction with family practice care in Slovenia.

OBJECTIVE To describe the level of patient satisfaction with family practice in Slovenia. DESIGN An internationally developed instrument for patients' evaluations of general practice care was used in a postal survey. SETTING A representative sample of 36 family practices in Slovenia. STUDY PARTICIPANTS Sixty consecutive patients in every practice were approached and offered a self-administered questionnaire. A total of 2160 questionnaires were handed out. MAIN OUTCOME MEASURE Percentages of patients reporting level of satisfaction on a 5-point Likert scale for the items in the questionnaire. RESULTS On average 58.2% of respondents rated the level of care received as excellent. Waiting in the waiting room was the item rated poorest (26.0%). Participants were also less satisfied with perceived time during the consultation (51.6%) and with connectional aspects of care: the feeling that family practitioners showed interest in their personal situation (46.5%); the feeling that family practitioners made it easy to explain problems (49.1%). On the other hand patients praised many other aspects of family practice care in Slovenia: confidentiality of medical records (77.0%); listening capacity of their family physicians (69.4%); being able to speak to the family practitioner on the 'phone (72%). CONCLUSIONS Patient satisfaction with family practice care in Slovenia was shown to be relatively high and can be compared to other European countries. The results showed areas in which quality improvement is required: organizational changes to shorten the waiting time in the waiting room and greater emphasis on communication skills.
Isolated SEPIC DC–DC Converter With Ripple-Free Input Current and Lossless Snubber

This paper proposes an isolated single-ended primary-inductor converter (SEPIC) dc–dc converter with ripple-free input current and lossless snubber. The proposed converter is based on a conventional isolated SEPIC converter to enable electrical isolation and high voltage gain using a coupled inductor. The input current ripple is significantly reduced by utilizing an auxiliary circuit that also functions as a lossless snubber circuit with an additional diode. Moreover, the maximum switch voltage stress is clamped to a low voltage by the snubber circuit. Therefore, a low voltage rating mosfet that has low $R_{{\rm{DS(on)}}}$ can be utilized as a main switch device. Hence, the total power efficiency is improved. Experimental results from a 100 W prototype, which are presented to verify the theoretic analysis and performance of the proposed converter.
The relationship between therapeutic injections and high prevalence of hepatitis C infection in Hafizabad, Pakistan

To determine the prevalence and routes of transmission of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, we collected sera in 1993 from a geographically based random sample of residents, and in 1994 identified 15 HCV-infected individuals (cases) and 67 age and sex matched uninfected individuals (controls). Initially we approached 504 households, and collected serum from a randomly selected household member in 309 (64%). Twenty persons (6·5%) had anti-HCV antibody; 31% percent had hepatitis B core antibodies, and 4·3% had hepatitis B surface antigen. In the case-control study, persons who received more therapeutic injections (categorized as averaging 1, 2–4, 5–9 or >10 injections per year in the previous 10 years) were more likely to be infected with HCV (odds ratio 0, 1·5, 2·5 and 6·9 respectively, P=0·008) compared to persons averaging 0 injections per year. Efforts to limit therapeutic injections to only those that are medically indicated and that use sterile equipment are essential in order to prevent transmission of HCV.
Gut microbiota‐associated bile acid deconjugation accelerates hepatic steatosis in ob/ob mice

Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely insufficient. The aim of this study was to elucidate the microbiota‐driven mechanisms involved in the development of nonalcoholic hepatic steatosis.
N3-phenacyluridine as a new type of antinociceptive compound in mice.

The antinociceptive activity of N3-phenacyluridine, a novel hypnotic, was examined with tail pinch, hot plate and acetic acid-induced abdominal constriction methods by intracerebroventricular (i.c.v.) injection to mice. In the first method, N3-phenacyluridine exerted antinociceptive activity after the i.c. v. injection at a dose of 0.5 micromol/mouse, although this activity was comparable to the activity of morphine (0.01 micromol/mouse, i.c.v.). In the second method, the activity of N3 -phenacyluridine was continued until 120 min after the injection at a dose of 0.5 micromol/mouse. In last, N3-phenacyluridine (0.1 micromol/mouse, i.c.v.) significantly decreased in the numbers of acetic acid-induced abdominal constriction as compared to the control (1% Tween 80 saline). The ED50 value of the antinociceptive activity of N3-phenacyluridine was 0.02 imol/mouse, i.c. v. The present paper demonstrated for the first time that N3-phenacyluridine belonging to oxopyrimidine nucleoside analogue possesses not only the hypnotic and sedative activities previously reported, but also antinociceptive activity.
Development of 111In-Labeled Liposomes for Vulnerable Atherosclerotic Plaque Imaging

Macrophage infiltration is a common characteristic feature of atherosclerotic-vulnerable plaques. Macrophages recognize phosphatidylserine (PS) exposed on the surface of apoptotic cells, which triggers the engulfment of the apoptotic cells by macrophages through phagocytosis. In this study, we prepared radiolabeled PS liposomes for detection of vulnerable plaques. Methods: PS liposomes were prepared by lipid film hydration. Phosphatidylcholine (PC) liposomes were prepared as controls. Liposomes (100 or 200 nm) were generated by an extruder to produce PS100, PS200, PC100, and PC200 liposomes. These were then radiolabeled by encapsulating 111In-nitrilotriacetic acid using an active-loading method. 111In liposomes were incubated with cultured macrophages for 2 h, and the uptake level was measured. For biodistribution studies, the 111In liposomes were injected intravenously into ddY mice. In addition, the 111In liposomes were injected into apolipoprotein E–deficient (apoE−/−) mice, and the aortas were harvested for autoradiography and oil red O staining. For SPECT imaging, 111In liposomes were injected intravenously into Watanabe heritable hyperlipidemic rabbits and scanned 48 h after injection. Results: The radiochemical yields were greater than 95% for all the prepared 111In liposomes. The level of in vitro uptake by macrophages was 60.5, 14.7, 32.0, and 14.4 percentage injected dose per milligram of protein for 111In-PS100, 111In-PC100, 111In-PS200, and 111In-PC200, respectively. In biodistribution studies, high spleen uptake was seen with PC liposomes. Liver uptake was high for all liposomes but was lowest with 111In-PS200. The blood half-lives were 3.2, 22.0, 3.6, and 7.4 min for 111In-PS100, 111In-PC100, 111In-PS200, and 111In-PC200, respectively. The distribution of 111In-labeled PS liposomes into atherosclerotic regions determined by autoradiography was well matched with the results of oil red O staining in apoE−/− mice. The target-to-nontarget ratios were 2.62, 2.23, 3.27, and 2.51 for 111In-PS100, 111In-PC100, 111In-PS200, and 111In-PC200, respectively. The aorta was successfully visualized by SPECT at 48 h after 111In-labeled PS liposome injection; however, high liver uptake was also observed. Discussion: From the in vitro uptake study, it has been demonstrated that macrophage targeting was accomplished by PS modification. Also, an atherosclerotic region was successfully detected by 111In-PS200 in apoE−/− mice and Watanabe heritable hyperlipidemic rabbits in vivo. Liposome modification to obtain slower blood clearance and lower liver uptake would be required to improve the SPECT images.
Health Behaviors Predict Higher Interleukin-6 Levels among Patients Newly Diagnosed with Head and Neck Squamous Cell Carcinoma

Background: Health behaviors have been shown to be associated with recurrence risk and survival rates in patients with cancer and are also associated with interleukin-6 (IL-6) levels, but few epidemiologic studies have investigated the relationship of health behaviors and IL-6 among cancer populations. The purpose of the study is to look at the relationship between five health behaviors, viz.: smoking, alcohol problems, body mass index (BMI; a marker of nutritional status), physical activity, and sleep and pretreatment IL-6 levels in persons with head and neck cancer. Methods: Patients (N = 409) were recruited in otolaryngology clinic waiting rooms and invited to complete written surveys. A medical record audit was also conducted. Descriptive statistics and multivariate analyses were conducted to determine which health behaviors were associated with higher IL-6 levels controlling for demographic and clinical variables among patients with newly diagnosed head and neck cancer. Results: While smoking, alcohol problems, BMI, physical activity, and sleep were associated with IL-6 levels in bivariate analysis, only smoking (current and former) and decreased sleep were independent predictors of higher IL-6 levels in multivariate regression analysis. Covariates associated with higher IL-6 levels were age and higher tumor stage, whereas comorbidities were marginally significant. Conclusion: Health behaviors, particularly smoking and sleep disturbances, are associated with higher IL-6 levels among patients with head and neck cancer. Impact: Treating health behavior problems, especially smoking and sleep disturbances, may be beneficial to decreasing IL-6 levels, which could have a beneficial effect on overall cancer treatment outcomes. Cancer Epidemiol Biomarkers Prev; 22(3); 374–81. ©2012 AACR.
Referral patterns for patients with high-risk thyroid cancer.

OBJECTIVE Knowledge of referral patterns for specialty cancer care is sparse. Information on both the need and reasons for referral of high-risk, well-differentiated thyroid cancer patients should provide a foundation for eliminating obstacles to appropriate patient referrals and improving patient care. METHODS We surveyed 370 endocrinologists involved in thyroid cancer management. From information in a clinical vignette, respondents were asked to identify the reasons they would need to refer a high-risk patient to a more specialized facility for care. We performed multivariable analysis controlling for hospital and physician characteristics. RESULTS Thirty-two percent of respondents reported never referring thyroid cancer patients to another facility. Of those that would refer a high-risk patient to another facility, the opportunity for a patient to enter a clinical trial was the most common reason reported (44%), followed by high-dose radioactive iodine (RAI) with or without dosimetry (33%), lateral neck dissection (24%), and external beam radiation (15%). In multivariable analysis, endocrinologists with a higher percentage of their practice devoted to thyroid cancer care were significantly less likely to refer patients to another facility (P = .003). CONCLUSION The majority of endocrinologists treating thyroid cancer patients report referring a high-risk patient to another facility for some or all of their care. Knowledge of the patterns of physician referrals and the likelihood of need for referral are key to understanding discrepancies in referral rates and obstacles in the referral process.
Problématiser la pratique enseignante pour mieux la comprendre : études de cas en sports collectifs à l’école maternelle

Le projet de cette contribution est de montrer comment des entretiens de formation inscrits dans le cadre de la problematisation technique permettent de mieux comprendre les pratiques enseignantes et les conceptions qui les sous-tendent. Nous ciblons notre etude sur l’enseignement des sports collectifs a l’ecole maternelle et sur la mobilisation du langage des eleves. Deux enseignantes, dans le cadre d’entretiens de formation, sont amenees a commenter la solution technique qu’elles ont produite en situation d’enseignement dans le but de faire construire des savoirs tactico-techniques aux eleves. En comparant les deux cas, nous voulons montrer comment une strategie d’entretien qui met en discussion des elements des solutions produites, fait apparaitre des dynamiques revelatrices des conceptions des enseignantes. Les resultats revelent que certains elements de la solution sont plus feconds que d’autres.
Prevalence and Effect of Cyberbullying on Children and Young People: A Scoping Review of Social Media Studies.

IMPORTANCE Social media has had a profound effect on how children and adolescents interact. While there are many benefits to the use of social media, cyberbullying has emerged as a potential harm, raising questions regarding its influence on mental health. OBJECTIVE To review existing publications that examine the health-related effects of cyberbullying via social media among children and adolescents. EVIDENCE REVIEW We searched 11 electronic databases from January 1, 2000, through January 17, 2012 (updated June 24, 2014). Studies were screened by 2 independent reviewers and were included if they reported primary research, described or evaluated the use of a social media tool in the context of cyberbullying, and were conducted with children or adolescents. Data were extracted by 1 reviewer and verified by a second. All studies were assessed by 2 reviewers for methodological quality using the Mixed Methods Appraisal Tool. Results were not pooled owing to heterogeneity in study objectives and outcomes; a narrative analysis is presented. FINDINGS Thirty-six studies in 34 publications were included. Most were conducted in the United States (21 [58.3%]), sampled middle and high school populations (24 [66.7%]), and included adolescents who were 12 to 18 years of age (35 [97.2%]). The median reported prevalence of cyberbullying was 23.0% (interquartile range, 11.0%-42.6%). Five studies reported inconsistent and/or weak correlations between cyberbullying and anxiety. Ten studies found a statistically significant association between cyberbullying and report of depression. Five studies investigated self-harm or suicidality, with conflicting results. Results indicate that the most common reason for cyberbullying is relationship issues, with girls most often being the recipients. Responses to cyberbullying are most often passive, with a pervasive lack of awareness or confidence that anything can be done. CONCLUSIONS AND RELEVANCE There is a consistent relationship across studies between cyberbullying and depression among children and adolescents; however, the evidence of the effect of cyberbullying on other mental health conditions is inconsistent. This review provides important information that characterizes cyberbullying within the context of social media, including attributes of the recipients and perpetrators, reasons for and the nature of bullying behaviors, and how recipients react to and manage bullying behaviors. This information is critical to the development of effective prevention and management strategies.
Indian hedgehog and β-catenin signaling: Role in the sebaceous lineage of normal and neoplastic mammalian epidermis

In mammalian epidermis, the level of β-catenin signaling regulates lineage selection by stem cell progeny. High levels of β-catenin stimulate formation of hair follicles, whereas low levels favor differentiation into interfollicular epidermis and sebocytes. In transgenic mouse epidermis, overexpression of β-catenin leads to formation of hair follicle tumors, whereas overexpression of N-terminally truncated Lef1, which blocks β-catenin signaling, results in spontaneous sebaceous tumors. Accompanying overexpression of β-catenin is up-regulation of Sonic hedgehog (SHH) and its receptor, Patched (PTCH/Ptch). In ΔNLef1 tumors Ptch mRNA is up-regulated in the absence of SHH. We now show that PTCH is up-regulated in both human and mouse sebaceous tumors and is accompanied by overexpression of Indian hedgehog (IHH). In normal sebaceous glands IHH is expressed in differentiated sebocytes and the transcription factor GLI1 is activated in sebocyte progenitors, suggesting a paracrine signaling mechanism. PTCH1 and IHH are up-regulated during human sebocyte differentiation in vitro and inhibition of hedgehog signaling inhibits growth and stimulates differentiation. Overexpression of ΔNLef1 up-regulates IHH and stimulates proliferation of undifferentiated sebocytes. We present a model of the interactions between β-catenin and hedgehog signaling in the epidermis in which SHH promotes proliferation of progenitors of the hair lineages whereas IHH stimulates proliferation of sebocyte precursors.
Fasting‐induced oxidative stress in very long chain acyl‐CoA dehydrogenase‐deficient mice

Hepatopathy and hepatomegaly as consequences of prolonged fasting or illnesses are typical clinical features of very long chain acyl‐CoA dehydrogenase (VLCACD) deficiency, the most common long‐chain fatty acid β‐oxidation defect. Supplementation with medium‐chain triglycerides (MCTs) is an important treatment measure in these defects, in order to supply sufficient energy. Little is known about the pathogenetic mechanisms leading to hepatopathy. Here, we investigated the effects of prolonged fasting and an MCT diet on liver function. Wild‐type (WT) and VLCAD knockout mice were fed with either a regular long‐chain triglyceride diet or an MCT diet for 5 weeks. In both groups, we determined liver and blood lipid contents under nonfasting conditions and after 24 h of fasting. Expression of genes regulating peroxisomal and microsomal oxidation pathways was analyzed by RT‐PCR. In addition, glutathione peroxidase and catalase activities, as well as thiobarbituric acid reactive substances, were examined. In VLCAD knockout mice fed with a long‐chain triglyceride diet, fasting is associated with excessive accumulation of liver lipids, resulting in hepatopathy and strong upregulation of peroxisomal and microsomal oxidation pathways as well as antioxidant enzyme activities and thiobarbituric acid reactive substances. These effects were even evident in nonfasted mice fed with an MCT diet, and were particularly pronounced in fasted mice fed with an MCT diet. This study strongly suggests that liver damage in fatty acid oxidation defects is attributable to oxidative stress and generation of reactive oxygen species as a result of significant fat accumulation. An MCT diet does not prevent hepatic damage during catabolism and metabolic derangement.