Miracle-dz/UniFAR-FTUs huggingface dataset:
The recombinant allergen‐based concept of component‐resolved diagnostics and immunotherapy (CRD and CRIT)

Current forms of allergy diagnosis and specific immunotherapy are performed with allergen extracts. Allergen extracts contain a variety of allergenic and nonallergenic components and their allergen content is often cumbersome to standardize. If used for diagnostic purposes, positive reactions to a given allergen extract will thus provide the information that an allergic subject is sensitized against extract components, but without identifying them. Likewise, extract-based immunotherapy cannot be adapted to the individual patient's sensitization pattern. Here we review progress in the field of molecular allergen characterization by recombinant DNA technology, leading to novel forms of component-resolved diagnostics (CRD) and immunotherapy (CRIT) based on recombinant allergens. Several studies have demonstrated advantages of recombinant allergen-based diagnosis. Using recombinant allergens in in vitro diagnostic devices, a patient's individual IgE reactivity profile can be quantitatively established. The presence of IgE to cross-reactive allergen components can thus be determined and used to predict clinically relevant sensitization to allergen sources which contain immunologically related allergens. Moreover it has been demonstrated that cocktails of recombinant allergens, matching the IgE epitope complexity present in natural allergen extracts, can be assembled. Component-resolved diagnosis will thus allow the precise selection of those molecules for specific immunotherapy to which a patient is actually sensitized. Recently, several recombinant hypoallergenic allergen derivatives have been developed for immunotherapy. The progress in allergen research achieved by the use of recombinant DNA technology holds promise that component-resolved diagnosis and immunotherapy may help refine the procedures of allergy diagnosis and immunotherapy in the coming decade and beyond.
Detection of rDNA ITS polymorphism in Rhizoctonia solani AG 2-1 isolates

The sequence variability of the ribosomal internal transcribed spacer regions ITS1 and ITS2, including the 5.8S gene, was investigated for Rhizoctonia solani isolates of anastomosis group (AG) 2-1. During PCR RFLP analysis of eight isolates, the restriction patterns of four isolates showed an excess of bands after restriction with the enzymes AvaII and/or HincII, which suggested the presence of more than one ITS region. By cloning the ITS region of six isolates sequence heterogeneity was detected in the isolates that showed an excess of bands in the PCR RFLP analysis; up to nine different ITS regions were identified within one isolate. The same level of diversity was found within the same isolate as among isolates. In the phylogenetic tree based on the rDNA ITS sequences of several AG 2-1 isolates, sequences derived from the same isolate did not form distinct clusters, questioning the relevance of further subdivision of heterogeneous AG 2-1 isolates based on the ITS region.
Neuronal cytoskeleton in synaptic plasticity and regeneration

During development, dynamic changes in the axonal growth cone and dendrite are necessary for exploratory movements underlying initial axo‐dendritic contact and ultimately the formation of a functional synapse. In the adult central nervous system, an impressive degree of plasticity is retained through morphological and molecular rearrangements in the pre‐ and post‐synaptic compartments that underlie the strengthening or weakening of synaptic pathways. Plasticity is regulated by the interplay of permissive and inhibitory extracellular cues, which signal through receptors at the synapse to regulate the closure of critical periods of developmental plasticity as well as by acute changes in plasticity in response to experience and activity in the adult. The molecular underpinnings of synaptic plasticity are actively studied and it is clear that the cytoskeleton is a key substrate for many cues that affect plasticity. Many of the cues that restrict synaptic plasticity exhibit residual activity in the injured adult CNS and restrict regenerative growth by targeting the cytoskeleton. Here, we review some of the latest insights into how cytoskeletal remodeling affects neuronal plasticity and discuss how the cytoskeleton is being targeted in an effort to promote plasticity and repair following traumatic injury in the central nervous system.
An in vitro Pathway from Embryonic Stem Cells to Neurons and Glia

Mouse embryonic stem (ES) cells can be induced to differentiate into neurons and glia in vitro. Induction protocols are straightforward and involve culture in the presence of retinoic acid. They result in an efficient conversion of undifferentiated ES cells to neural cells. Mature neurons produced have the key physiological, morphological and molecular properties of primary cultured neurons derived from the central nervous system. Most significantly, they form functional chemical synapses that utilize either glutamate, GABA or glycine as neurotransmitters. ES cell-derived glial cells also correspond well with their normal counterparts. During induction, ES cells undergo a series of developmental steps that resemble key stages in the early mouse embryo. This supports the hypothesis that the in vitro pathway is a valid model of the normal developmental pathway leading to neurons and glia. The in vitro system combines three experimental strengths. It is suitable for genetic manipulation, affords large numbers of cells and allows precise manipulation of the culture environment. It is thus suitable for a wide variety of mechanistic studies in the areas of neural development and cell biology.
Application of a new material (β-TCP/collagen composites) in extraction socket preservation: an experimental study in dogs.

PURPOSE A bone defect model simulating an extraction socket with buccal dehiscence was designed to investigate the usefulness of a composite of beta-tricalcium phosphate (β-TCP) and a collagen sponge, β-TCP/collagen (TCP/Col) for socket preservation. MATERIALS AND METHODS Following the extraction of the maxillary second and third premolars of 13 beagle dogs, a bone defect with buccal dehiscence (5 × 3 × 7 mm) was prepared. The defects were filled with either TCP/Col, ? -TCP, collagen, or left intact (control) and evaluated at 4 and 8 weeks after surgery. A total of three micro-computed tomography (micro-CT) images were selected, and the area size occupied by the newly formed bone and residual TCP was measured. Newly formed bone and residual TCP in the bone defect site of the specimens was also measured and evaluated. RESULTS No evidence of postoperative infection was found in all cases. At 4 weeks after surgery, the TCP granule was retained in the bone defects and active bone formation was observed in the TCP/Col group and the β-TCP group, whereas in the collagen and the control groups, connective tissue grew into the defect. In the TCP/Col and β-TCP groups, morphologically well-preserved alveolar ridges were observed; most TCP granules grafted in the defects were resorbed and only a few residuals were evident at 8 weeks after surgery. CONCLUSIONS These results exhibited that the TCP/Col composites could sufficiently maintain bone width and height for the preservation of the extraction socket with buccal dehiscence while preventing epithelial in-growth. In addition, TCP/Col in an easily handled spongeous form could provide a better intraoral manipulation capability than TCP granules alone and was considered to be suitable as a bone grafting material used for alveolar ridge preservation.
Method Effects: The Problem With Negatively Versus Positively Keyed Items

Using confirmatory factor analyses, we examined method effects on Rosenberg's Self-Esteem Scale (RSES; Rosenberg, 1965) in a sample of older European adults. Nine hundred forty nine community-dwelling adults 60 years of age or older from 5 European countries completed the RSES as well as measures of depression and life satisfaction. The 2 models that had an acceptable fit with the data included method effects. The method effects were associated with both positively and negatively worded items. Method effects models were invariant across gender and age, but not across countries. Both depression and life satisfaction predicted method effects. Individuals with higher depression scores and lower life satisfaction scores were more likely to endorse negatively phrased items.
The adenosinergic system in cancer

High amounts of adenosine are released in the tumor mass. Depending on the levels of adenosine, as well as on the receptor subtypes that are expressed by immune cells, adenosine can affect tumor growth in different fashions. Specifically targeting CD73, the rate-limiting enzyme for the extracellular generation of adenosine, or the A3 receptor offers new therapeutic strategies to limit tumor progression.
Gender differences in human sepsis.

BACKGROUND In animal studies, gender differences were related to hormonal and immunologic changes that were associated with an increased susceptibility to sepsis in males. OBJECTIVE In a prospective study, gender differences in patients with surgical sepsis were evaluated in terms of survival, sex hormones, and proinflammatory as well as anti-inflammatory mediators. SETTING Surgical intensive care unit of a university hospital. PATIENTS Fifty-two patients (19 women and 33 men) with surgical sepsis. MEASUREMENTS AND MAIN RESULTS In a prospective study, tumor necrosis factor alpha and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), total testosterone, and 17-beta estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severity of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found in the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hospital-mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor necrosis factor continuously increased in men after diagnosis of sepsis, with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction), whereas no difference was found for interleukin 6 bioactivity. Women displayed enhanced interleukin 10 levels compared with men from day 1 to day 10 that reached a significant difference on days 3 and 5 (P<.05). Total testosterone levels were below the normal range for men, and estradiol levels were initially increased in both men and postmenopausal women, with higher levels for women. CONCLUSIONS In this prospective study, gender differences were confirmed in human sepsis, with a significantly better prognosis for women, which may be related to increased levels of anti-inflammatory mediators. The hypothetical different ratio of proinflammatory and anti-inflammatory mediators may be important for further therapeutic interventions in sepsis.
Ganglion-Specific Impairment of the Norepinephrine Transporter in the Hypertensive Rat

Hypertension is associated with enhanced cardiac sympathetic transmission, although the exact mechanisms underlying this are still unknown. We hypothesized that defective function of the norepinephrine uptake transporter (NET) may contribute to the sympathetic phenotype of the spontaneously hypertensive rat, and that this may occur before the development of hypertension itself. The dynamic kinetics of NET were monitored temporally using a novel fluorescent assay of the transporter in cultured postganglionic sympathetic neurons from the cardiac stellate ganglion, the superior cervical ganglion, the celiac ganglia/superior mesenteric ganglia, and the renal sympathetic chain. All NET activity was blocked by desipramine. NET rate was significantly impaired in cardiac stellate sympathetic neurons from the prehypertensive spontaneously hypertensive rat compared with age-matched normotensive Wistar-Kyoto rats. A similar response was seen in hypertensive spontaneously hypertensive rats stellate sympathetic neurons. However, no reduction in transporter rate was observed at either age in the other major noncardiac sympathetic ganglia. Depolarization of cardiac stellate neurons by electrical field stimulation further potentiated the difference in transporter rate observed between the hypertensive and normotensive rats at both developmental ages. In conclusion, dysregulation of the norepinephrine transporter in the hypertensive rat is ganglion-specific, where NET impairment in the stellate neurons may contribute to the increased cardiac norepinephrine spillover seen in hypertension.
Pan computed tomography versus selective computed tomography in stable, young adults after blunt trauma with moderate mechanism: A cost-utility analysis

BACKGROUND Pan computed tomography (PCT) of the head, cervical spine, chest, abdomen, and pelvis is a valuable approach for rapid evaluation of severely injured blunt trauma patients. A PCT strategy has also been applied for the evaluation of patients with lower injury severity; however, the cost-utility of this approach is undetermined. The advantage of rapidly identifying all injuries via PCT must be weighed against the risk of radiation-induced cancer (RIC). Our objective was to compare the cost-utility of PCT with selective computed tomography (SCT) in the management of blunt trauma patients with low injury severity. METHODS A Markov model–based, cost-utility analysis of a hypothetical cohort of hemodynamically stable, 30-year-old males evaluated in a trauma center after motor vehicle crash was used. CT scans are performed based on the mechanism of injury. The analysis compared PCT with SCT over a 1-year time frame with an analytic horizon over the lifespan of the patients. The possible outcomes, utilities of health states, and health care costs including RIC were derived from the published medical literature and public data. Costs were measured in US 2010 dollars, and incremental effectiveness was measured in quality-adjusted life-years (QALYs) with 3% annual discounted rates. Multiway sensitivity analyses were performed on all variables. RESULTS The total cost for blunt trauma patients undergoing PCT was $15,682 versus $17,673 for SCT. There was no difference in QALYs between the two populations (26.42 vs. 26.40). However, there was a cost savings of $75 per QALY for patients receiving PCT versus SCT ($594 per QALY vs. $669 per QALY). CONCLUSION PCT enables surgeons to identify and rule out injuries promptly, thereby reducing the need for inpatient observation. The risk of RIC is low following a single PCT. This cost-utility analysis finds PCT based on mechanism to be a cost-effective use of resources. LEVEL OF EVIDENCE Economic and value-based evaluations, level II.
Disposition and Metabolism of Ticagrelor, a Novel P2Y12 Receptor Antagonist, in Mice, Rats, and Marmosets

Ticagrelor is a reversibly binding and selective oral P2Y12 antagonist, developed for the prevention of atherothrombotic events in patients with acute coronary syndromes. The disposition and metabolism of [14C]ticagrelor was investigated in mice, rats, and marmosets to demonstrate that these preclinical toxicity species showed similar metabolic profiles to human. Incubations with hepatocytes or microsomes from multiple species were also studied to compare with in vivo metabolic profiles. The routes of excretion were similar for both oral and intravenous administration in mice, rats, and marmosets with fecal excretion being the major elimination pathway accounting for 59 to 96% of the total radioactivity administered. Urinary excretion of drug-related material accounted for only 1 to 15% of the total radioactivity administered. Milk samples from lactating rats displayed significantly higher levels of total radioactivity than plasma after oral administration of ticagrelor. This demonstrated that ticagrelor and/or its metabolites were readily transferred into rat milk and that neonatal rats could be exposed to ticagrelor-related compounds via maternal milk. Ticagrelor and active metabolite AR-C124910 (loss of hydroxyethyl side chain) were the major components in plasma from all species studied and similar to human plasma profiles. The primary metabolite of ticagrelor excreted in urine across all species was an inactive metabolite, AR-C133913 (loss of difluorophenylcyclopropyl group). Ticagrelor, AR-C124910, and AR-C133913 were the major components found in feces from the three species examined. Overall, in vivo metabolite profiles were qualitatively similar across all species and consistent with in vitro results.
Betamethasone alteration of the one-hour glucose challenge test in pregnancy.

OBJECTIVE To determine if betamethasone administration alters the one-hour (50-g) glucose challenge test (GCT) and, if so, to determine the duration of this effect. STUDY DESIGN Pregnant women with singleton gestations eligible to receive antenatal betamethasone (24-34 weeks) with no evidence of infection, diabetes mellitus, hepatic or pancreatic disease, betamimetic therapy or prolonged steroid use were invited to participate. Betamethasone (12 mg) was administered intramuscularly upon admission and repeated in 24 hours. After an 8-hour fast, a 50-g GCT was administered 24 hours (day 1) and 72 hours (day 3) after the second betamethasone injection. Plasma glucose samples were drawn one hour after the glucose challenge. Statistical analysis utilized the McNemar exact test. RESULTS Seven patients, all with normal GCTs 7-10 days outside the study period, were enrolled. Six had abnormal GCT results on day 1 (P = .03). Three had abnormal results on day 3. CONCLUSION Betamethasone administration results in abnormal one-hour GCTs in pregnant women.
Family size, adolescents’ schooling and the Demographic Transition: Evidence from Brazil

The goal of this paper is to address whether and how the changing family sizes of cohorts of adolescents born pre- and post-demographic transition are associated with increasing schooling of Brazilian adolescents. Decomposition analyses of nationally representative data demonstrate that, although a higher proportion of post-demographic transition cohorts live in smaller families, they also suffer a larger disadvantage from being in larger families than pre-demographic transition cohorts. Additional case studies and comparative works are needed to disentangle the mechanisms behind the dynamic association between sibship size and adolescents’ educational attainment found in Brazil.
Heat-modifiable outer membrane proteins of Neisseria meningitidis and their organization within the membrane

Neisseria meningitidis group B serotype 2 strain M986 contains two predominant outer membrane proteins, with apparent molecular weights of 41,000 (protein b) and 28,000 (protein e). Heating of outer membrane vesicles at 56 degrees C for 20 min caused much of b** to disaggregate and denature into b (41,000 daltons). In contrast, protein e could be rapidly solubilized by SDS at room temperature into its monomeric state (e*), but it was not converted to its final higher apparent molecular weight of 28,000 (e) unless heated at 100 degrees C for 2 min. We propose that protein b exists in the membrane as trimers or tetramers in a transmembrane configuration and that protein e exists as subunits on the exterior surface of the outer membrane and has a highly ordered tertiary structure.
Efficacy of platelet-rich plasma on wound healing in rabbits.

BACKGROUND The purpose of this study was to evaluate if the healing of full-thickness skin wounds was accelerated by platelet-rich plasma (PRP). METHODS Four 2.5 x 2.5-cm full-thickness skin wounds were created on the backs of 15 New Zealand white rabbits. One wound on each animal received 0.3, 0.6, or 0.9 ml PRP, and the fourth wound served as a control. Seven and eight animals were sacrificed after 1 or 2 weeks, respectively, to determine histomorphometrically the epithelialization rate, contraction rate, healing rate, tissue fill, and volume fractions of fibroblasts, neutrophils, macrophages, and blood vessels. RESULTS Only the 0.6- and 0.9-ml groups had significantly lower contraction rates than the controls after 2 weeks (P <0.05). Although no statistically significant differences were found in other parameters between the PRP-treated wounds and the controls, the PRP treatment led to increases in average epithelialization rates and volume fraction of blood vessels at both time periods. The PRP also seemed to have the most positive effect on healing rate, tissue fill, and volume fraction of fibroblasts during week 1 compared to week 2. CONCLUSIONS The PRP treatment enhanced healing in full-thickness wounds by reducing the contraction rate with a trend toward acceleration of the epithelial migration and the angiogenic response. Further studies with larger sample sizes should be conducted to improve statistical sensitivity. Longer time intervals and modifications of PRP volume should also be explored to evaluate the long-term efficacy of PRP on wound healing.
Genital Chlamydia trachomatis infections in Lithuanian women invited for screening via newspaper advertisement: a pilot study

There are only single reports concerning prevalence of genital Chlamydia trachomatis infections in Lithuania.1, 2 The aim of this study was to investigate the prevalence of C trachomatis infections in a group of Lithuanian women. Sexually active women, with genital complaints (n = 147), living in the seaport of Klaipeda, Lithuania (400 000 inhabitants) were invited for screening of genital C trachomatis via the local newspaper. The median and mean age of the women tested was 29 years. The women were interviewed, examined gynaecologically, and samples taken from the cervix. Genital samples were kept frozen at –70°C for 3 months until transportation to Uppsala and polymerase chain …
Differential induction of tumor necrosis factor by bacteria expressing rough and smooth lipopolysaccharide phenotypes

The lipid A portion of the lipopolysaccharide (LPS) molecule of gram-negative bacteria has the ability to turn on the production of tumor necrosis factor (TNF) in macrophage cells. The question addressed in this paper was whether the presence of the polysaccharide moiety on the LPS molecule had any bearing on this ability. The question was asked (i) by using isolated LPS from a series of Salmonella mutants having progressively less polysaccharide attached to the lipid A portion of the molecule and (ii) by using whole bacteria expressing alternatively the smooth or rough LPS phenotype. Isolated LPS and bacteria were examined for their abilities to induce bioactive TNF in the mouse macrophage cell line RAW 264.7. The results indicated that the presence of long- or short-chain polysaccharide moieties had no bearing on the ability of the isolated LPS molecule to induce TNF. However, the presence of long-chain polysaccharides attached to the lipid moiety on the intact smooth bacterium was associated with a decreased ability to induce TNF. To test whether the bacteria were inducing TNF by a cell (bacterium)-to-cell (macrophage) contact mechanism or through a releasable product, the bacteria were removed from direct contact with the macrophage cells by using a Transwell filter insert. Under these conditions the rough bacteria continued to induce TNF, while the smooth bacteria were no longer capable of doing so. When filtrates from the bacteria were examined in the Limulus amebocyte lysate assay, the results showed that the rough bacteria were releasing approximately a log order more Limulus amebocyte lysate activity than the smooth bacteria. The results of this study suggest that rough bacteria may be superior inducers of TNF compared with their smooth counterparts because of a greater propensity to shed their LPS.