Miracle-dz/UniFAR-FTUs huggingface dataset:
Normal CD40‐mediated activation of monocytes and dendritic cells from patients with hyper‐IgM syndrome due to a CD40 pathway defect in B cells

Patients with X‐linked hyper‐IgM syndrome [CD40 ligand (CD40L) deficiency] are prone to infections by intracellular parasites. It has been suggested that this susceptibility is caused by defective macrophage activation through the CD40L‐CD40 pathway. We studied the CD40‐mediated activation of monocytes and dendritic cells from patients affected with a CD40L+ hyper‐IgM syndrome characterized by a defect of B lymphocyte responses to CD40 agonists. We show that the CD40‐induced production of IL‐6, IL‐8 and TNF‐α by monocytes, and IL‐12 by dendritic cells, and expression of the activation markers CD83, the co‐stimulatory molecules CD86 and CD80, and HLA‐DR antigens were all similar in patient and control cells. This observation is consistent with the clinical characteristics of the syndrome: a defect of immunoglobulin switch but no susceptibility to opportunistic infections, as observed in CD40L‐deficient patients. These observations suggest that CD40‐mediated activation pathways could be, at least in part, different in B and monocytic/dendritic cell lineages.
Treatment of Freiberg Disease with Intra-articular Dorsal Wedge Osteotomy and Absorbable Pin Fixation

Background: The purpose of this study was to evaluate the outcome of intra-articular dorsal wedge osteotomy and absorbable pin fixation for the treatment of Freiberg disease. Methods: From January of 1997, to July of 2003, 12 patients with symptomatic Freiberg disease had intra-articular dorsal wedge osteotomy through the affected metatarsal head fixed with absorbable polyglycolide pins. All 12 patients were women with an average age of 36 (range 16 to 59) years. The Smillie stage of necrosis ranged from II to V. Active range-of-motion exercise was allowed after 4 weeks of short-leg walking cast wear, and weightbearing on the forefoot was allowed after radiographic union was achieved. The mean followup was 45 (range 22 to 84) months. Results: Radiographically, solid healing of all osteotomies was observed at an average of 10 (range 8 to 16) weeks. There was no evidence of displacement, osteolysis, sinus formation, or progression of osteonecrosis at final followup. Pain measurement on a visual analog scale had improved significantly from an average of 8.0 to 2.3 (p < 0.05). The range of motion of the metatarsophalangeal joint increased by a mean of 26 (range 5 to 60) degrees. All patients were satisfied with the results and would have the surgery again. Conclusions: In patients with Freiberg disease, intra-articular dorsal wedge osteotomy restores congruity of the metatarsophalangeal joint, and fixation with absorbable pins provides adequate fixation and avoids a second procedure for implant removal.
Population Pharmacokinetics and Pharmacodynamics of Zidovudine in HIV‐Infected Infants and Children

The purpose of this study was to assess the population pharmacokinetics (PK) and pharmacodynamics (PD) of zidovudine (ZDV) in infants and children. This evaluation includes 394 subjects who participated in Pediatric AIDS Clinical Trials Group (PACTG) Study 152 and received either ZDV alone or in combination with didanosine. The most significant PK covariate was age, with infants < 2 years of age having reduced size‐adjusted clearance. ZDV exposure was weakly related to maximal reduction in immune complex‐dissociated (ICD) p24 antigen but not to reduction at 6 months. Mild chronic anemia occurred in 7.6% of subjects with ZDV average concentration < 1.3 μM (350 ng/mL) versus in 23.4% subjects with higher ZDV concentrations (p < 0.001). There was a direct linear relationship between hemoglobin and ZDV levels. It was concluded that ZDV oral clearance is reduced in infants compared to older children. This lower clearance leads to higher ZDV exposure in infants and contributes to increased hematologic toxicity.
Different signaling responses to anti‐proliferative agents in human aortic and venous smooth muscle cells

Proliferation of smooth muscle cells (SMCs) contributes to the stenosis of coronary arteries and vascular grafts. Local delivery of anti‐proliferative drugs can prevent vascular stenosis. To understand the cellular responses to anti‐proliferative agents, we investigated the signaling events in cultured human aortic SMCs (ASMCs), saphenous venous SMCs (VSMCs), and dermal fibroblasts (DFs) in response to paclitaxel or etoposide. Cellular mitochondrial and proliferative activities were examined with the methylthiazoletetrazolium (MTT) dye reduction and the bromodeoxyuridine (BrdU) incorporation assay, respectively. Cell proliferation was almost completely suppressed by paclitaxel or etoposide, but apoptosis was achieved in only about 50% of cells at the highest drug concentrations, suggesting the presence of compensatory mechanisms to prevent apoptosis. Examination of three important signaling pathways revealed significant differences between ASMCs, VSMCs, and DFs. Treatment with either paclitaxel or etoposide caused a transient phosphorylation/activation of p42 MAPK in ASMCs and DFs, but had no effect on phospho‐p42/44 MAPK in VSMCs. High‐dose etoposide enhanced p38 MAPK activation in ASMCs, but not in VSMCs. The p38 inhibitor, PD169316, partially inhibited etoposide‐induced ASMC apoptosis, but induced apoptosis in VSMCs. The effects of etoposide and paclitaxel on Akt also differed between ASMCs and VSMCs. These observations indicate that ASMCs and VSMCs differ in the response of signaling pathways to anti‐proliferative agents. In ASMCs, p42/44 MAPK appears to serve a pro‐survival role, whereas p38 MAPK is a pro‐apoptotic regulator. In contrast, p38 MAPK is an important pro‐survival regulator in VSMCs and p42/44 MAPK appears to play a minor role in responding to anti‐proliferative drugs. J. Cell. Biochem. 99: 835–844, 2006. © 2006 Wiley‐Liss, Inc.
Isoniazid prophylaxis in a slum area.

The District of Columbia Department of Public Health, in cooperation with the U.S. Public Health Service, selected Census Tract 49 for testing response to isoniazid prophylaxis in a slum area. Only 55 per cent of the estimated 9,000 residents in this community were tuberculin tested. Approximately 1,400 reactors were identified, but an additional 2,000 who would have been eligible for prophylaxis were never identified because of failure either to contact them or to test them. Of the 1,400 identified reactors, approximately 45 per cent took at least one half of the pills prescribed during 17 two-week periods. Part of the failure to identify all reactors or to continue prophylaxis in those identified was ascribable to the mobility and lack of motivation on the part of the residents in the area. The experience from this study did not indicate that chemoprophylaxis among reactors should become a city-wide policy in the District of Columbia.
PATENT PROTECTION, OPTIMAL LICENSING, AND INNOVATION WITH ENDOGENOUS ENTRY

How does patent policy affect innovation when patent licensing is crucial for firms? To address this question, the present study incorporates voluntary patent licensing between an innovator and followers, as discussed in the literature of industrial organization, into a dynamic general equilibrium model. Unlike previous studies, both the licensing fee and the number of licensees are endogenously determined by the innovator’s maximization and the free-entry condition. Using this model, we show that strong patent protection does not always enhance innovation, economic growth, and welfare. Furthermore, the extended analysis provides the policy implication that the effect of patent policy depends on how difficult further innovation is without patent licensing of the current leading technology.
Synthesis and accumulation of polyamines in rat liver during chemical carcinogenesis

The activities of L‐ornithine decarboxylase (EC 4.1.1.17) and S‐adenosyl‐L‐methionine decarboxylase (EC 4.1.1.50) exhibited marked fluctuations in the livers of rats fed 4‐dimethylaminoazobenzene. After 1 month of dye feeding the activity of ornithine decarboxylase rose to a level about six times higher than that of controls and the activity of adenosyl‐methionine decarboxylase was more than twice the initial control level. These elevations were transient, and returned to near normal values within the next 2 months. Four months after the commencement of the azo‐dye diet, ornithine and adenosylmethionine decarboxylase activities showed a second distinct stimulation and appeared to remain high until liver tumors appeared. In contrast, the activity of tyrosine aminotransferase (EC 2.6.1.5) initially decreased but increased after 3 to 6 months to levels slightly exceeding the control values. The biphasic response of the two decarboxylases to the carcinogen appeared to be specific for the liver since both enzyme activities showed a sharp decrease in the kidney during the first 3 months of dye feeding followed by a transient increase 1 month later. The concentration of putrescine in the liver roughly followed the fluctuations of ornithine decarboxylase activity, being about twice the control level in carcinogentreated rats. Spermidine and spermine concentrations were normal although the activities of spermidine synthase (EC 2.5.1.16) and spermine synthase appeared to be lower in animals fed the carcinogenic diet than in normal controls. The response of liver ornithine decarboxylase, adenosylmethionine decarboxylase and tyrosine aminotransferase to growth hormone, glucagon and hydrocortisone was measured several times during the course of the azo‐dye diet. There were only small changes, if any, in the stimulation of tyrosine aminotransferase by growth hormone or hydrocortisone whereas the stimulation by glucagon was totally lost. The striking response of ornithine decarboxylase to porcine growth hormone was markedly reduced, and the moderate stimulation elicited by glucagon completely disappeared during the carcinogenic diet. The response of adenosylmethionine decarboxylase to growth hormone remained unchanged, while the marginal stimulation evoked by either glucagon or hydrocortisone in normal rats totally disappeared after 4 months of dye feeding. Elevated activities of ornithine decarboxylase and adenosylmethionine decarboxylase, together with a distinctly reduced response of these enzymes to hormonal stimulations, thus appear to be characteristics of rat liver undergoing chemical carcinogenesis.
Metabolic inactivation of five glycidyl ethers in lung and liver of humans, rats and mice in vitro

1. Some glycidyl ethers (GE) have been shown to be direct mutagens in short-term in vitro tests and consequently GE are considered to be potentially mutagenic in vivo. However, GE may be metabolically inactivated in the body by two different enzymatic routes: conjugation of the epoxide moiety with the endogenous tripeptide glutathione (GSH) catalysed by glutathione S-transferase (GST) or hydrolysis of the epoxide moiety catalysed by epoxide hydrolase (EH). 2. The metabolic inactivation of five different GE, the diglycidyl ethers of bis phenol A (BADGE), 4,4'-dihydroxy-3,3',5,5'-tetramethylbiphenyl (Epikote YX4000) and 1,6- hexanediol (HDDGE)and the GE of 1-dodecanol (C12GE)and o-cresol (o-CGE), has been studied in subcellular fractions of human, C3H mouse and F344 rat liver and lung. 3. All GE were chemically very stable and resistant to aqueous hydrolysis, but were rapidly hydrolysed by EH in cytosolic and microsomal fractions of liver and lung. The aromatic GE were very good substrates for EH. In general, microsomal EH is more efficient than cytosolic EH in hydrolysis of GE, and human microsomes are more efficient than rodent microsomes. 4. The more water-soluble GE, o-CGE and HDDGE, were good substrates for GST whereas the more lipophilic GE, YX4000 and C12GE, were poor substrates for GST. In general, rodents are more efficient in GSH conjugation of GE than humans. 5. In general, the epoxide groups of YX4000 are the most and those of HDDGE the least efficiently inactivated of the five GE under study. For the other three GE no general trend was observed: the relative efficiency of inactivation varied with organ and species. 6. The large variation in metabolism observed with five representative GE indicate that GE have variable individual properties and should not be considered as a single, homogenous class of compounds.
Arterial hypertension increases intracranial pressure in cat after opening of the blood-brain barrier.

BACKGROUND Increased permeability for small solutes in brain capillaries means that a change in hydrostatic capillary pressure may influence transcapillary fluid exchange according to the Starling fluid equilibrium, and a high arterial pressure may cause transcapillary fluid filtration and raised intracranial pressure. This could be of clinical relevance in states of disrupted blood-brain barrier such as meningitis and after a severe head injury, especially since these patients quite often are spontaneously hypertensive, and hypertensive therapy is sometimes used to increase cerebral perfusion pressure. This study on cat investigated the long-term relation between arterial pressure and intracranial pressure in a state of disrupted blood-brain barrier. METHOD Endotoxin was given intrathecally to open the blood-brain barrier and depress cerebral autoregulation. Arterial pressure was increased by about 30 mm Hg during 5 hours by dopamine and angiotensin II infusion. The immediate fall in intracranial pressure after normalization of blood pressure reflects the blood volume component of an intracranial pressure increase. RESULTS Increased arterial pressure had no effect on intracranial pressure before endotoxin. Endotoxin infusion increased intracranial pressure from the normal value of 10 to 12 mm Hg. and at steady state by almost 10 mm Hg. Intracranial pressure increased further after the arterial pressure increase. At steady state (achieved within 5 hours), this increase was almost as great as the arterial pressure increase, and about 80% persisted when measured directly after normalization of the arterial pressure. CONCLUSION Increased arterial pressure in a state of disrupted blood-brain barrier increases intracranial pressure, mainly because of brain edema. This stresses that arterial hypertension may be deleterious in conditions such as meningitis or after a brain trauma.
Personal Nostalgia, World View, Memory, and Emotionality

Batcho's 1995 Nostalgia Inventory was completed by 210 respondents, 88 males and 122 females, ranging in age from 5 to 79 years old. Subjects scoring high on the Nostalgia Inventory rated the past more favorably than did subjects scoring low on the inventory but did not differ in ratings of the present or future. High-scoring individuals rated themselves more emotional, with stronger memories, need for achievement, and preference for activities with other people, but not as less happy, risk or thrill seeking, religious, logical, easily bored, or expecting to succeed. In a second study, 113 undergraduates, 32 men and 81 women, completed measures of nostalgia, memory, and personality. High-scoring subjects showed no advantage in free recall over low-scoring subjects but recalled more people-oriented autobiographical memories. Individuals scoring high on nostalgia were no more optimistic, pessimistic, or negatively emotional but scored higher on a measure of emotional intensity. Personal nostalgia was distinguished from social-historical nostalgia and world view. Results were discussed with respect to major theoretical approaches.
In vitro treatment of dendritic cells with tacrolimus: impaired T-cell activation and IP-10 expression.

BACKGROUND High doses (10(-6)-10(-8) M) of tacrolimus (FK506) were reported to induce a type-2 T-helper cell (Th2)-promoting function in developing dendritic cells (DC). We used a therapeutic dose (2.4 x 10(-9 )M) of tacrolimus to investigate its effect on human monocyte-derived DC. METHODS Using untreated and treated immature and mature DC we compared T cell-activating capacity, surface marker expression, T cell and DC cytokine profile and transcription of genes coding for a panel of DC function-related molecules. RESULTS Tacrolimus-treated mature DC had reduced T-cell stimulatory capacity. Although interleukin (IL)-12 production of DC was impaired, they did not promote Th2 development as T cells activated by tacrolimus-treated DC produced less interferon (IFN)-gamma, IL-4 and IL-10. The up-regulation of the T-cell activation marker CD69 and the production of IL-2 were impaired. In addition, tacrolimus-treated DC produced less IP-10 (CXCL10), which is known to be involved in allograft rejection. Other molecules related to DC function remained unchanged. CONCLUSIONS Tacrolimus treatment reduces the ability of DC to stimulate T cells and the impaired production of DC-derived IP-10 (CXCL10) and IL-12 might play a role in the immunosuppressive action of tacrolimus.
Analysis of the Duodenal Microbiome in Autistic Individuals: Association With Carbohydrate Digestion

Objectives: There is evidence that symptoms of maldigestion or malabsorption in autistic individuals are related to changes in the indigenous microbiota. Analysis of colonic bacteria has revealed microbial dysbiosis in children with autism; however, characteristics of the duodenal microbiome are not well described. In the present study the microbiome of the duodenal mucosa of subjects with autism was evaluated for dysbiosis, bacteria overgrowth, and microbiota associated with carbohydrate digestion. The relationship between the duodenal microbiome and disaccharidase activity was analyzed in biopsies from 21 autistic subjects and 19 children without autism. Methods: Microbiota composition was determined by 16S ribosomal RNA gene sequencing, and disaccharidase activity via biochemical assays. Results: Although subjects with autism had a higher frequency of constipation (P < 0.005), there was no difference in disaccharidase activity between groups. In addition, no differences in microbiome diversity (species richness and evenness) were observed. Bacteria belonging to the genus Burkholderia were more abundant in subjects with autism, whereas members of the genus Neisseria were less abundant. At the species level, a relative decrease in abundance of 2 Bacteroides species and Escherichia coli was found in autistic individuals. There was a positive correlation between the abundance of Clostridium species, and disaccharidase activity, in autistic individuals. Conclusions: There are a variety of changes at the genus and species level in duodenal microbiota in children with autism that could be influenced by carbohydrate malabsorption. These observations could be affected by variations in individual diets, but also may represent a more pervasive dysbiosis that results in metabolites that affect the behavior of autistic children.
Lime and Compost Promote Plant Re-Colonization of Metal-Polluted, Acidic Soils

The revegetation of soils affected by historic depositions of an industrial complex in Central Chile was studied. The plant re-colonization from the existing soil seed bank and changes in the physico-chemical properties of the soil were evaluated in field plots amended with lime and/or compost. We found that the application of lime and/or compost decreased the Cu2+ ion activity in the soil solution and the exchangeable Cu in the soil, showing an effective Cu immobilization in the topsoil. Whereas lime application had no effect on plant productivity in comparison with the unamended control, the application of compost and lime+compost increased the plant cover and aboveground biomass due to the higher nutrient availability and water-holding capacity of the compost-amended soils. Although the Cu2+ activity and the exchangeable Cu were markedly lower in the amended soils than in the unamended control, the shoot Cu concentrations of Lolium spp. and Eschscholzia californica did not differ between the treatments.
Does early arthritis clinic organisation improve outcomes? What evidence is there? A systematic review.

OBJECTIVES To perform a systematic review aimed to identify studies addressing the effect of the establishment of a structured organisation programme, named early arthritis clinic (EAC), finalized to manage patients with early arthritis (EA) or suspected early rheumatoid arthritis (ERA). METHODS A literature search was performed until May 2012 using electronic databases. Additional information was obtained through a hand and grey literature search. Primary and secondary outcomes and eligibility criteria have been defined. RESULTS The search provided a total of 3367 citations and, after the selection process, 11 non randomised controlled trials were selected, including a total of 8240 participants. The efficacy of EAC did clearly emerge with regard to reduction of the referral lag time and of the time to treatment (secondary outcomes). Only two studies met the primary outcomes: one study demonstrated that the EAC contributed to reducing disease activity and radiographic progression but not functional disability, while another reported a reduction of pain after a 6-12-month period of follow-up. CONCLUSIONS Whether the establishment of EAC would improve the prognosis of EA in terms of primary outcomes such as clinical, functional and radiologic progression compared to patients managed outside from EAC does appear a still poorly addressed issue in the literature, which should be recognised as an urgent unmet need by the rheumatology community to gain more evidence-based information on this topic.
The Usability of Moodle Learning Management System As a Web- Support Tool in Teaching Chemistry

The purpose of this study was to investigate the usability of Moodle Learning Management System [LMS] as a web-support tool in teaching chemistry at second- ary school. For this purpose Moodle LMS was used as the web-support tool for teaching “Chemistry in Our Lives” unit in the 9th grade high school chemistry cur- riculum and the its effect on students’ academic achievement and interest towards chemistry were investigated. The sample of the study was composed of total of 60 ninth grade students from two different classes in a high school in Erzurum. In this study in which instrumental case study was utilized as the research method, “Chem- istry in Our Lives” unit was taught through Context-based ARCS Instructional Model and Moodle LMS was used as the web-support tool. At the end of the im- plementation an achievement test was administered and semi-structured interviews with 13 students were done. The students' achievement test scores were compared with Kruskal-Wallis test according to the frequency of using Moodle LMS. Semi- structured interviews were subjected to descriptive analysis. The results showed that Moodle LMS which was used as a web-supported tool had positive effects on stu- dents’ achievement and interest towards chemistry. In addition, the problems en- countered during Moodle LMS implementation have been identified and various suggestions have been made to overcome these problems.