Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of Human Dendritic Cell Maturation Using Transfection with RNA Encoding a Dominant Positive Toll-Like Receptor 41

Maturation of dendritic cells (DC) is critical for the induction of Ag-specific immunity. Ag-loaded DC matured with LPS, which mediates its effects by binding to Toll-like receptor 4 (TLR4), induce Ag-specific CTL in vitro and in vivo in animal models. However, clinical use of LPS is limited due to potential toxicity. Therefore, we sought to mimic the maturation-inducing effects of LPS on DC by stimulating TLR4-mediated signaling in the absence of exogenous LPS. We developed a constitutively active TLR4 (caTLR4) and demonstrated that transfection of human DC with RNA encoding caTLR4 led to IL-12 and TNF-α secretion. Transfection with caTLR4 RNA also induced a mature DC phenotype. Functionally, transfection of DC with caTLR4 RNA enhanced allostimulation of CD4+ T cells. DC transfected with RNA encoding the MART (Melan-A/MART-1) melanoma Ag were then used to stimulate T cells in vitro. Cotransfection of these DC with caTLR4 RNA enhanced the generation of MART-specific CTL. This CTL activity was superior to that seen when DC maturation was induced using either LPS or a standard mixture of cytokines (TNF-α, IL-6, IL-1β, and PGE2). We conclude that transfection of DC with RNA encoding a functional signaling protein, such as caTLR4, may provide a new tool for studying TLR signaling in DC and may be a promising approach for the induction of DC maturation for tumor immunotherapy.
The effect of periodontal treatment on C-reactive protein: A clinical study

Background: Chronic periodontitis in amultifactorial inflammatory disease which is caused by various microorganisms. Many studies have found close association between chronic periodontitis and C-reactive protein (CRP). CRPis an inflammatory marker which increases in all inflammatory condition. Aims and Objective: The present clinical study was designed to show the effect of periodontal treatment on the CRP levels of gingival crevicular fluid and to determine the effect of nonsurgical therapy in minimizing the CRP levels in chronic generalized periodontitis. Material and Method: Gingival crevicular fluid was collected using a micro capillary pipette that was hand calibrated at every 1 mm till 10 mm, from selected sites in the subjects on the 1st, 14th and 45th days. Results and Conclusion: Decreased CRP levels of gingival crevicular fluid were observed at the end of the study. There was a 37% reduction in probing pocket depth and 45% gain in clinical attachment level and a reduction of about 57% after 14 days and 90% reduction of CRP levels in gingival crevicular fluid after 45 days. Thus, the results show that the presence of CRP level is more significant in gingival crevicular fluid and confirms the underlying inflammatory component of the disease activity in chronic periodontitis.
First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055

Objective: To investigate endometrial safety by assessment of endometrial biopsy samples and the tolerability and efficacy of the special Actaea or Cimicifuga racemosa extract (CR BNO 1055). Design: Four hundred postmenopausal women with symptoms related to estrogen deficiency were enrolled into a prospective, open-label, multinational, multicenter study. Treatment duration (daily dose corresponds to 40 mg of herbal drug) was 52 weeks. To determine the probability of endometrial hyperplasia and more serious adverse endometrial outcome, the point estimator and upper limit of 95% CI were calculated. Descriptive statistics was used to assess the secondary endpoints. Results: Endometrial safety has been proven because no case of hyperplasia or more serious adverse endometrial outcome occurred (point estimate: 0.0; upper limit of 95% CI: 0.011). Endometrial thickness, which was measured by endovaginal ultrasonography, did not show an increase. The number and intensity of hot flushes were markedly decreased. The dropout rate was less than 10%. The overall tolerability was good. Conclusions: The lack of endometrial proliferation and improvement of climacteric complaints as well as only few gynecologic organ-related adverse events are reported for the first time after a treatment period of 1 year. Due to the improved benefit:risk ratio, it must be assumed that the Cimicifuga racemosa special extract BNO 1055 is a safe alternative for treatment of climacteric complaints.
Polysialic acid and the formation of oculomotor synapses on chick ciliary neurons

The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) participates in a variety of developmental processes, including axonal guidance and cell migration. PSA's function in these contexts stems from its ability to reduce cell interactions. The present study examines the regulation of PSA expression during formation of the calyciform synapse by the oculomotor axons on chick ciliary neurons. Prior to synaptogenesis, PSA is abundantly and uniformly expressed on the surface of the ciliary neuron body. However, at the time synaptic bonds start to form, as reflected in the localized accumulation of synaptic vesicles, PSA is lost from the point of synaptic contact. Thereafter, PSA is progressively lost from the ciliary neuron surface as the calyx grows. The dense mats of pseudodendritic‐like somatic spines, which extend from the postsynaptic cell body, form an exception. These spines, which are known to undergo morphological remodeling, retain PSA expression until the end of embryogenesis. The experimental removal of PSA did not affect synaptogenesis itself, in that no significant changes were observed in the surface covered by the calyx, the number of spine aggregates, the size of acetylcholine receptor clusters, the cell surface area covered by these receptors, or the ultrastructure of the calyx, spine mats, and active zones. Together, these observations suggest that the synapse eliminates PSA as a part of its normal development and that the loss of PSA from the site of axon‐target interaction may serve to stabilize structures formed during synaptogenesis. J. Comp. Neurol. 446:244–256, 2002. © 2002 Wiley‐Liss, Inc.
Good longterm survival after primary living donor liver transplantation for solitary hepatocellular carcinomas up to 8 cm in diameter.

OBJECTIVES There is controversy over whether hepatocellular carcinoma (HCC) should be primarily treated with living donor liver transplantation (LDLT) if liver resection (LR) can be effective. This retrospective study was conducted to compare survival outcomes in patients treated with either modality for solitary HCC measuring ≤8 cm in diameter. METHODS Outcomes in patients with solitary HCC primarily treated by LDLT were analysed. Patients with solitary HCC of similar sizes with or without microvascular invasion primarily treated with LR were selected at a ratio of 6 : 1 for comparison. RESULTS In-hospital mortality amounted to 0% and 1.3% in the LDLT (n = 50) and LR (n = 300) groups, respectively (P = 0.918). Complication rates were 34% and 20% in the LDLT and LR groups, respectively (P = 0.027). Rates of 1-, 3-, 5- and 10-year overall survival were 98%, 94%, 89% and 83%, respectively, in the LDLT group and 95%, 85%, 76% and 56%, respectively, in the LR group (P = 0.013). Rates of 1-, 3-, 5- and 10-year disease-free survival were 96%, 90%, 87% and 81%, respectively, in the LDLT group and 81%, 64%, 57% and 40%, respectively, in the LR group (P < 0.0001). CONCLUSIONS Living donor liver transplantation surpassed LR in survival outcomes, achieving a 10-year overall survival rate 1.5 times as high and a 10-year disease-free survival rate twice as high as those facilitated by LR. However, it entailed more complications, in addition to the inevitable risks to the donor.
Denoising for Generalized Sidelobe Canceller

The generalized sidelobe canceller (GSC) efficiently realizes the optimal linearly constrained minimum variance (LCMV) beamformer and delivers excellent beamforming results by reducing directional interference and noise. However, when the input signals are contaminated by other type of noises, such as background and diffused noises, the overall performance of GSC can be even worse than the traditional delay-and-sum beamformers. In this paper, we investigate the application of the spatially adaptive multiwavelet (MWT) denoising technique to the GSC in an environment with severe diffused noise. Comparing with the traditional scalar wavelets, the multiwavelets can better characterize the noise information in the signal such that better denoising performance can be achieved. Different approaches for integrating the GSC and the multiwavelet denoiser were studied. It is found that by adding two denoisers, one to the fixed constrained part and another to the final GSC output, an improvement of 2dB in SNR can be achieved as compared with the traditional GSC method
Pericoronary Adipose Tissue: A Novel Therapeutic Target in Obesity-Related Coronary Atherosclerosis

Inflammation plays a crucial role in the development and destabilization of atherosclerotic plaques in coronary vessels. Adipose tissue is considered to act in paracrine manner, which modulates a number of physiological and pathophysiological processes. Perivascular adipose tissue has developed specific properties that distinguish it from the fat in other locations. Interestingly, its activity depends on several metabolic conditions associated with insulin resistance and weight gain. Particularly in obesity perivascular fat seems to change its character from a protective to a detrimental one. The present review analyzes literature in terms of the pathophysiology of atherosclerosis, with particular emphasis on inflammatory processes. Additionally, the authors summarize data about confirmed paracrine activity of visceral adipose tissue and especially about pericoronary fat influence on the vascular wall. The contribution of adiponectin, leptin and resistin is addressed. Experimental and clinical data supporting the thesis of outside-to-inside signaling in the pericoronary milieu are further outlined. Clinical implications of epicardial and pericoronary adipose tissue activity are also evaluated. The role of pericoronary adipose tissue in obesity-related atherosclerosis is highlighted. In conclusion, the authors discuss potential therapeutical implications of these novel phenomena, including adipokine imbalance in pericoronary adipose tissue in the setting of obesity, the influence of lifestyle and diet modification, pharmaceutical interventions and the growing role of microRNAs in adipogenesis, insulin resistance and obesity. Key teaching points: • adipose tissue as a source of inflammatory mediators • changes in the vascular wall as a result of outside-to-inside signaling • anatomy, physiology, and clinical implications of epicardial and pericoronary adipose tissue activity • adipokines and their role in obesity-related atherosclerosis • therapeutic perspectives and future directions
B Cell Depletion With an Anti‐CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation

Alloreactive memory T cells mediate accelerated allograft rejection and transplant tolerance resistance. Recent studies have shown that B cell deficient–μMT mice fail to mount donor‐specific memory T cell responses after transplantation. At the same time, other studies showed that pretransplant B cell depletion using rituximab (IgG1 anti‐CD20 mAb) combined with cyclosporine A promoted the survival of islet allografts in monkeys. In this study, we investigated the effect of anti‐CD20 antibody‐mediated B cell depletion on the memory T cell alloresponse in mice. Wild‐type and anti‐OVA TCR transgenic mice were treated with an IgG2a anti‐CD20 monoclonal antibody, which depleted nearly all B cells in the peripheral blood and secondary lymphoid organs but spared some B cells in the bone marrow. B cell depletion did not affect the direct alloresponse but resulted in a marked increase of indirect alloresponse after skin transplantation of naïve mice. Furthermore, in allosensitized mice, anti‐CD20 mAb treatment enhanced the reactivation of allospecific memory T cells and accelerated second set rejection of skin allografts. This suggests that the effect of anti‐CD20 antibodies on alloimmunity and allograft rejection might vary upon the nature of the antibodies as well as the circumstances under which they are delivered.
Laser stimulation of single auditory nerve fibers

One limitation with cochlear implants is the difficulty stimulating spatially discrete spiral ganglion cell groups because of electrode interactions. Multipolar electrodes have improved on this some, but also at the cost of much higher device power consumption. Recently, it has been shown that spatially selective stimulation of the auditory nerve is possible with a mid‐infrared laser aimed at the spiral ganglion via the round window. However, these neurons must be driven at adequate rates for optical radiation to be useful in cochlear implants. We herein use single‐fiber recordings to characterize the responses of auditory neurons to optical radiation.
The role of antibody in recovery from alphavirus encephalitis

Alphaviruses infect neurons in the brain and spinal cord and cause acute encephalomyelitis in a variety of mammals. The outcome of infection is determined by whether the neurons survive infection and this, in turn, is determined by the virulence of the virus and the age of the host at the time of infection. We have been studying Sindbis virus (SV) infection i of mice as a model system for alphavirus‐induced encephalomyelitis. Investigation of intracerebral infection of weanling mice with two different strains of SV bas allowed us to analyze the role of the immune response in protection from fatal disease virulent NSV strain) and in CLEARANCE of virus from the nervous system during non‐fatal disease (less virulent SV AR339 strain). Neutralizing and non‐neutralizing antibodies to the El and E2 surface glycoproteins can protect mice from fatal NSV infection when given before or after infection, while T cells are not protective, The mechanism of antibody‐mediated protection is not known, but it is likely that more than one mechanism Is involved and that different mechanisms are involved in pre‐infection and post‐infection treatment protection. Clearance of infectious virus from the nervous system of mice during recovery from non‐fatal disease is accomplished by antibodies to the E2 glycoprotein. The process does not involve damage to the infected neurons and is independent of complement and mononuclear cells. Bivalent antibody is required and binds to the surface of the infected cell. Initially, release of virus by budding from the cell surface is prevented and, subsequently, intracellular virus replication is inhibited possibly through antiviral mechanisms induced in co‐operation with interferon. This non lytic mechanism for control of virus infection results in the prolonged presence of viral RNA in tissue and the need for prolonged intrathecal synthesis of antiviral antibody by B cells within the central nervous system.
Examining the support needs of ageing family carers in developing future plans for a relative with an intellectual disability

Background: Planning for the future care of adults with an intellectual disability after the main family carer ceases their care, continues to be a sensitive and difficult time posing challenges for service providers internationally. Limited research has been undertaken on this topic because until recently, people with intellectual disability usually pre-deceased their parents. This study examined ageing carers’ preferences for future care and the support systems required to make such future plans. Methods: The study was conducted in one region of the United Kingdom with a high proportion of family carers. A mixed methods design was employed. In Stage 1, a structured questionnaire was used to collate information on the health, caregiving demands and future planning preferences of 112 parent and sibling carers; aged 60–94 years. In Stage 2, 19 in-depth semistructured interviews were undertaken with a sample of carers to explore a range of issues around future planning. Findings: Over half of the carers were lone carers, mainly female, with many reporting a wide range of health problems. A third of these carers reported that their caregiving resulted in high levels of anxiety. The main preference of the carers was for the person to remain in the family home, with either the family and/or paid staff to support them. A minority of parent carers preferred the person to move into the home of a sibling, although some favoured the person moving to a residential facility with other people with intellectual disabilities. The majority of carers did not want their relative to move into an older people’s residential/nursing facility. In the qualitative data, four main themes were identified around future planning: unremitting apprehension, the extent of planning, obstacles encountered and solutions for future planning. Avoidance, lack of guidance and a lack of appropriate residential provision were cited as obstacles to making future plans compounded by the emotional upset experienced by carers in thinking about the future. Conclusion: Findings of this study clearly identify the emotional, informational and practical supports required by these ageing family carers. These findings have national and international relevance in influencing how governments and service providers support parent and sibling carers to proactively plan for the future, and in the development of both in-home and out-of-home options when a family carer can no longer provide care. This is more urgent than ever given the growing numbers of older persons with intellectual disabilities in future decades.
T1ρ MRI quantification of arthroscopically confirmed cartilage degeneration

Nine asymptomatic subjects and six patients underwent T1ρ MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2‐3 months postarthroscopy, using sagittal T1‐weighted and axial and coronal T1ρ MRI, from which spatial T1ρ relaxation maps were calculated from segmented T1‐weighted images. Median T1ρ relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (P < 0.001), and median T1ρ exceeded asymptomatic articular cartilage median T1ρ by 2.5 to 9.2 ms. In eight observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1ρ was elevated in five, but in all observations, large foci of increased T1ρ were observed. It was determined that T1ρ could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes. Magn Reson Med 63:1376–1382, 2010. © 2010 Wiley‐Liss, Inc.
Age- and gender-specific antibacterial prescribing in Norway.

OBJECTIVES To describe the use of antibacterials among outpatients in Norway and to explore patterns of age- and gender-specific use. METHODS Data were extracted from the Norwegian Prescription Database (NorPD), a complete register of all dispensed prescriptions in Norway, in the period 1 July 2005-30 June 2006. NorPD contains data at an individual level. We extracted patients who had received an antibacterial for systemic use. Results were shown as population prevalences for the total population. RESULTS A total of 1.1 million persons had at least one prescription for an antibacterial dispensed. The mean population prevalence of antibacterial use was 24% in total (28% and 19% for women and men, respectively). Population prevalence changed markedly between different age groups and between genders. Children (<5 years) and older elderly people (>or=75 years) were high consumers. Females, in general, used more than males. Use by the different subgroups of antibacterials differed between gender and between different age groups. beta-Lactamase-sensitive penicillins was the most prevalent antibacterial group in all age groups except for women >or=75 years, for whom penicillins with extended spectrum were the most frequently used. Individuals defined as high users (using more than 60 DDDs/year) represented 3% of the population who were using antibacterials. These patients were older and used co-medication more often than other users of antibacterials. CONCLUSIONS Over 1 year, a quarter of the total population used antibacterials. Patterns of use and types of drugs used differed markedly between genders and between different age groups.
[Trends in antimicrobial utilization in a university hospital, 1990-1996].

OBJECTIVE There is a worldwide concern about rational drug use, more specifically related to antimicrobial utilization. In developing countries, few resources are intended for monitoring on rational drug use. Moreover, there are limited data on the use of antimicrobial agents in hospitals. A study was carried out to describe patterns of use of antimicrobial agents over a 7-year period (1990 to 1996). METHODS The study was conducted in a 690-bed tertiary care university hospital in Porto Alegre, Brazil. Hospital records were reviewed to identify inpatient antibiotics use. Results were expressed in defined daily dose per 100-beds/day. Cluster analysis was performed to determine the trends in use of individual agents. RESULTS Antimicrobials use increased year after year, from 83.8 DDD per 100 beds-day in 1990 to 124.58 DDD per 100 beds-day in 1996. Penicillins were the drug group mostly used (39.6%), followed by cephalosporins (15.0%), aminoglycosides (14.4%), sulfonamides (12.8%), glycopeptides (3.6%), and lincosamides (3.1%). These groups were responsible for around 90% of all agents used. The use of antimicrobial agents was divided into thirteen groups based on cluster analysis. CONCLUSIONS Antimicrobial use increased dramatically in the study period, and this increase was significantly higher when compared to other studies. When newer alternative agents became available in the hospital, the use of already existing drugs decreased and in some cases remained relatively stable. After implementing specific interventions, such as an effort for the correct use of cefoxitin, the expected changes in use were observed.