Miracle-dz/UniFAR-FTUs huggingface dataset:
Considerations and methodology for trialing ziconotide.

BACKGROUND Before long-term intrathecal analgesic therapy is initiated, patients often undergo a spinal analgesia trial. Ziconotide is a nonopioid intrathecal analgesic used to manage severe chronic pain, and a variety of methods have been used to trial ziconotide. OBJECTIVES The purpose of this review is to compare and discuss the different methods of ziconotide trialing. METHODS Various databases (i.e., PubMed, Excerpta Medica, Cumulative Index to Nursing and Allied Health Literature, Biological Abstracts, Cochrane Database of Systematic Reviews, EMBASE, International Pharmaceutical Abstracts, and Google Scholar) and association meeting abstracts were searched with the use of the terms ziconotide, Prialt, trial, and trialing. In addition, a search was conducted for abstracts/posters presented at a variety of association meetings. RESULTS Nine sources, including one expert opinion piece, were identified. Three methods of ziconotide trialing were discovered: continuous infusion, limited-duration infusion, and bolus injection. Results indicate that patients often achieve analgesia during trialing, regardless of the trialing method. Adverse events reported during ziconotide trialing studies were similar to those reported during ziconotide clinical trials. Preliminary evidence suggests that both effectiveness and safety may be dose-related. In 3 studies the value of ziconotide trialing in predicting long-term patient response to ziconotide therapy was investigated; however, the results were preliminary. The expert opinion piece from 2008 recommended trialing ziconotide via continuous infusion, using a starting dose of 1.2 mcg/d and dose increases of 1.2 mcg/d every 12 to 24 hours, for up to 3 days; the trial may be extended in some cases. LIMITATIONS Given the small samples size and lack of controlled ziconotide trialing studies, it is currently not possible to determine the relative safety and effectiveness of different methods of ziconotide trialing, nor is it possible to determine if trialing is predictive of patient response to long-term ziconotide therapy. CONCLUSIONS All 3 methods of ziconotide trialing appear to be viable options, and no method can be considered superior on the basis of the evidence presented in this review. Controlled studies comparing ziconotide trialing methods may be warranted.
Characterization of human brown adipose tissue by chemical-shift water-fat MRI.

OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.
Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells

Wild-type p53 has recently been shown to repress transcription from several cellular and viral promoters. Since p53 mutations are the most frequently reported genetic defects in human cancers, it becomes important to study the effects of mutations of p53 on promoter functions. We, therefore, have studied the effects of wild-type and mutant human p53 on the human proliferating-cell nuclear antigen (PCNA) promoter and on several viral promoters, including the herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were cotransfected with a wild-type or mutant p53 expression vector and a plasmid containing a chloramphenicol acetyltransferase reporter gene under viral (or cellular) promoter control. As expected, expression of the wild-type p53 inhibited promoter function. Expression of a p53 with a mutation at any one of the four amino acid positions 175, 248, 273, or 281, however, correlated with a significant increase of the PCNA promoter activity (2- to 11-fold). The viral promoters were also activated, although to a somewhat lesser extent. We also showed that activation by a mutant p53 requires a minimal promoter containing a lone TATA box. A more significant increase (25-fold) in activation occurs when the promoter contains a binding site for the activating transcription factor or cyclic AMP response element-binding protein. Using Saos-2 cells that do not express p53, we showed that activation by a mutant p53 was a direct enhancement. The mutant forms of p53 used in this study are found in various cancer cells. The activation of PCNA by mutant p53s may indicate a way to increase cell proliferation by the mutant p53s. Thus, our data indicate a possible functional role for the mutants of p53 found in cancer cells in activating several important loci, including PCNA.
Decreased Nitric Oxide Levels Stimulate Osteoclastogenesis and Bone Resorption Both in Vitro and in Vivo on the Chick Chorioallantoic Membrane in Association with Neoangiogenesis

High nitric oxide (NO) levels inhibit osteoclast (OC)‐mediated bone resorption in vivo and in vitro, and nitrate donors protect against estrogen‐deficient bone loss in postmenopausal women. Conversely, decreased NO production potentiates OC bone resorption in vitro and is associated with in vivo bone loss in rats and humans. Previously, we reported that bone sections from rats administered aminoguanidine (AG), a selective inhibitor of NO production via inducible NO synthase, exhibited both increased OC resorptive activity as well as greater numbers of OC. Here, we investigated further whether AG promoted osteoclastogenesis, in addition to stimulating mature OC function, using a modified in vivo chick chorioallantoic membrane (CAM) system and an in vitro chick bone marrow OC‐like cell developmental model. AG, focally administered in small agarose plugs placed directly adjacent to a bone chip implanted on the CAM, dose‐dependently elicited neoangiogenesis while stimulating the number, size, and bone pit resorptive activity of individual OC ectopically formed in vivo. In addition to enhancing OC precursor recruitment via neoangiogenesis, AG also exerted other vascular‐independent effects on osteoclastogenesis. Thus, AG promoted the in vitro fusion and formation from bone marrow precursor cells of larger OC‐like cells that contained more nuclei per cell and exhibited multiple OC differentiation markers. AG stimulated development was inversely correlated with declining medium nitrite levels. In contrast, three different NO donors each dose‐dependently inhibited in vitro OC‐like cell development while raising medium nitrite levels. Therefore, NO sensitively regulates OC‐mediated bone resorption through affecting OC recruitment (angiogenesis), formation (fusion and differentiation), and bone resorptive activity in vitro and in vivo. Possibly, the stimulation of neoangiogenesis and OC‐mediated bone remodeling via AG or other pro‐angiogenic agents may find clinical applications in reconstructive surgery, fracture repair, or the treatment of avascular necrosis.
Off-pump versus on-pump coronary artery bypass grafting surgery in high-risk patients: PRAGUE-6 trial at 30 days and 1 year.

AIMS Off-pump coronary artery bypass graft surgery (OPCAB) is an established alternative to on-pump surgical revascularization. Previous studies in patients with low or intermediate risk showed no significant differences between off-pump and on-pump surgical revascularization. The aim of this study was to compare the two techniques in patients with high operative risk. METHODS PRAGUE-6 is a prospective randomized single-center study of 206 patients, with an additive EuroSCORE ≥ 6, scheduled for isolated coronary surgery: Group A - on-pump (n = 108) versus Group B - off-pump (n = 98). The primary outcome was a combined endpoint of all-cause deaths, stroke, myocardial infarction, or renal failure requiring new hemodialysis, within 30 days and 1 year after randomization. All data were analyzed using the "intention-to-treat" principle. RESULTS Early postoperative myocardial infarction was detected in 12.1% (A) vs. 4.1% (B) of patients (P = 0.048, hazard ratio 0.32, 95% CI 0.11-0.99). There was a significantly higher incidence of primary combined end-point in group A (20.6% vs. 9.2%, P = 0.028, HR 0.41, 95% CI 0.19-0.91) in the first 30 days, but not after 1 year (30.8% vs. 21.4%, P = 0.117, HR 0.65, CI 0.37-1.12). CONCLUSION Off-pump surgical revascularization in patients with high operative risks can significantly reduce the incidence of major postoperative complications during the first 30 days. There was no statistically significant difference in the incidence of these complications after 1 year.
Feed Efficiency and Norepinephrine Turnover in Iron Deficiency

Norepinephrine turnover and energetic efficiency studies were conducted in three groups of male Sprague-Dawley rats placed on low iron diets for 5 weeks on weaning. Iron-deficient rats had significant anemia (hematocrit < 20%) and growth retardation relative to pair-fed and ad libitum fed controls who received the same diet plus weekly iron dextran injections. Energetic efficiency over a 7-day period was nearly 30% less in anemic animals. This was associated with significantly higher rates of norepinephrine turnover in brown adipose tissue (110%) and heart (330%) with significant hypertrophy in both tissues. There was no difference in body composition in ad libitum groups. Plasma triiodothyronine and thyroxine were reduced by 37% in iron deficients compared to controls. Thus 39% increase in caloric requirements in iron deficiency is associated with increased sympathetic and perhaps thermogenic activity in brown adipocytes.
Left Ventricular Dysfunction after Closure of Large Patent Ductus Arteriosus

Changes in left ventricular dimensions and performance were studied in 43 patients after transcatheter occlusion or surgical ligation of patent ductus arteriosus. The patients were assigned to 2 groups based on their ductal diameter: ≥ 3.1 mm to group A (n = 27) and ≤ 3 mm to group B (n = 16). The mean age and weight of the groups were comparable. Before intervention, group A had a significantly larger mean left ventricular end-diastolic diameter than group B, while all patients had normal shortening fraction and ejection fraction. Within 1 month after intervention, left ventricular end-diastolic diameter showed a trend towards regression while shortening fraction and ejection fraction decreased significantly in group A. There were no significant changes in these parameters in group B. Between 1 and 6 months after intervention, left ventricular performance improved in most of the group A patients who were followed up. We conclude that closure of large ductus arteriosus in children leads to significant immediate deterioration of left ventricular performance, which appears to recover within a few months. Echocardiographic study before hospital discharge is recommended in these patients. Serious deterioration of ventricular performance after closure may warrant the use of angiotensin converting enzyme inhibitors.
Farmer typology formulation accounting for psychological capital: implications for on-farm entrepreneurial development

ABSTRACT Understanding and accounting for the heterogeneity of small farmers is critical for informing development pathways to improve the performance of smallholder irrigation. Using multivariate analysis, this study sought to develop farmer typologies in and around irrigation schemes and used these to inform strategies for on-farm entrepreneurship development. The research uniquely integrates psychological capital in defining farmer typologies, to capture individual features of each farmer, otherwise missed by the generic sustainable livelihoods framework literature. The study affirms the need to focus on psychological capital and concludes that heterogeneity among small-scale irrigators should be accounted for in future agricultural and rural development programmes.
Systems of Augmentative and Alternative Communication (SAACs) in Spain: A Systematic Review of the Educational Practices Conducted in the Last Decade

Systems of Augmentative and Alternative Communication (SAACs) encompass a variety of forms of expression used to enhance the communication skills of people with disabilities and/or communication impairments. This paper compiles educational practices carried out in Spain using SAACs in the last decade. A systematic review of scientific research databases enabled a descriptive and qualitative analysis of the 25 case studies out of 88 that met the established inclusion criteria. The aim of this analysis was to obtain a global perspective of the main lines of action, as well as to identify its nature according to the beneficiary, context, aims, and typology of the SAACs implemented through the application of an evaluation grid. This evaluation grid tool arose in a broader European Project entitled AAC@ School for Social Inclusion. The results of this systematic review provide researchers and educators with evidence to apply SAACs with individuals with communication impairments, regardless of their age, gender, or the impairment or functional diversity they suffer from and could be applied in other European contexts.
Natural and manufactured objects activate the fusiform face area

&NA; Recent fMRI studies indicate that the anterior fusiform gyrus (the fusiform face area, FFA) is specialized for face recognition. However, the analyses used to determine face selectivity have not ruled out the possibility that other object categories produce significant activation in the FFA, relative to baseline. In the current fMRI study, we use a conservative hypothesis testing approach to show that FFA activation is not selective for faces. Rather, the FFA response is almost completely explained by a graded response in which faces produce more activation than either manufactured or natural objects, but those categories produce a statistically greater response than the baseline task. These findings question whether the FFA can be interpreted as a specialized module for face recognition. NeuroReport 13:935‐938 © 2002 Lippincott Williams & Wilkins.
Behavioral and temperamental features of children with Costello syndrome

Costello syndrome (CS) is a rare genetic condition due to germline mutations in HRAS proto‐oncogene and characterized by increased birth weight, postnatal growth retardation, distinctive facial appearance, typical medical problems (including feeding problems in the neonatal period), cutaneous anomalies, and developmental delay. Outgoing personality has often been noted in case reports, but few studies have focused specifically on the behavioral aspects of CS. A preliminary survey described irritability in younger patients with improvement between age 2 and 4, but a standardized psychometric tool was not used. A second study using the Child Behavior Checklist (CBCL) showed relatively high (albeit subclinical) levels of internalizing problems. These descriptive investigations lacked a control group. We describe a comparative survey to evaluate the behavioral and temperamental features of children with CS. We conducted a cross‐sectional assessment using the CBCL and the Emotionality, Activity, Shyness, Sociability (EAS) temperament questionnaire to evaluate behavior and temperament in 11 CS children (2 years 5 months to 9 years) comparing them to 33 gender‐ and age‐matched children without disability. The results suggest that the high levels of internalizing problems found before age 4 in CS patients might decrease with age. They also point to possible “hyperemotionality. ” Further studies using a larger sample size and IQ‐matched control groups are needed to more accurately characterize individuals with this rare syndrome. © 2006 Wiley‐Liss, Inc.
Further Results for Perron-Frobenius Theorem for Nonnegative Tensors

For a nonnegative irreducible tensor, we give distribution properties of its eigenvalues. In particular, the spectral radius of a nonnegative irreducible tensor with positive trace is proved to be the unique eigenvalue on the spectral circle. Unlike the matrix setting, we give an example to present that this type of tensor is not always primitive. Thus, for a nonnegative irreducible tensor, the primitivity is a sufficient condition only for the spectral radius to be the unique eigenvalue on the spectral circle. Also, the stochastic tensor is defined, and we show that every nonnegative irreducible tensor with unit spectral radius is diagonally similar to a certain irreducible stochastic tensor. Based on this result, the minimax theorem for tensors is proved by using an alternative approach. Further, with the help of the minimax theorem, we illustrate that the problem of finding the spectral radius (largest singular value) of a nonnegative irreducible square (rectangular) tensor can be converted into a convex optimization problem. Additionally, we give an equivalent condition of irreducible nonnegative tensors. By this condition, one can easily determine whether or not a nonnegative tensor is irreducible.
Ultraviolet protective properties of branded and unbranded sunglasses available in the Indian market in UV phototherapy chambers.

BACKGROUND Patients receiving phototherapy for various dermatoses are at increased risk of eye damage due to ultraviolet (UV) rays. They are prescribed UV protective sunglasses by dermatologists but their exact protecting effects are not known. AIM To study the ultraviolet protective properties of branded and unbranded UV protective sunglasses available in the Indian market, in UV phototherapy chambers. METHODS Sixteen different branded and unbranded UV protective sunglasses were collected from two opticians in Mumbai. Baseline irradiance of the UV chamber was calculated by exposing the photosensitive probe of UV photometer in the chamber. Then, the photosensitive probe of the UV photometer was covered with the UV protective glass to be studied and irradiance was noted. Such readings were taken for each of the UV protective sunglasses. The percentage reduction in the UV rays' penetration of different UV protective sunglasses was calculated. RESULTS Thirteen sunglasses provided > 80% reduction in UVA rays penetration, of which four were branded (out of the four branded studied) and nine were unbranded (out of the 12 unbranded studied). More than 70% reduction in UVB penetration was provided by 12 sunglasses, which included 10 unbranded and two branded sunglasses. CONCLUSION All branded sunglasses provided good protection against UVA penetration, but UVB protection provided by both branded and unbranded sunglasses was not satisfactory. A few unbranded sunglasses had poor efficacy for UVA and UVB spectra; one branded glass had poor efficacy for protection against the UVB spectrum. The efficacy of sunglasses used for phototherapy should be assessed before use.
Optical multichannel (optimul) platelet aggregometry in 96-well plates as an additional method of platelet reactivity testing

Platelet reactivity testing is important for the diagnosis of bleeding disorders, and increasingly to optimise anti-platelet therapy. Traditional light transmission aggregometry is considered the gold standard, whilst 96-well plate aggregometry, founded on similar principles, provides a higher throughput screening method. Despite the widespread use of both, methodologies and outputs vary widely between laboratories. We report a methodological approach towards providing a standardised optical detection of platelet aggregation (optimul method) based upon 96-well plate aggregometry. Individual wells of half-area 96-well plates were coated with gelatine and one of seven concentrations of arachidonic acid (AA), adenosine diphosphate (ADP), collagen, epinephrine (EPI), ristocetin, TRAP-6 amide or U46619, before being lyophilised, vacuum-sealed, foil-packed and stored at room temperature for up to 24 weeks. For platelet testing, 40 µl of platelet-rich plasma was added to each well. Platelet aggregation was determined by changes in light absorbance, release of ATP/ADP by luminescence and release of thromboxane (TX) A2 by ELISA. Some experiments were conducted in the presence of aspirin (30 µM) or prasugrel active metabolite (PAM; 3 µM). Optimul plates stored for up to 12 weeks permitted reliable detection of concentration-dependent platelet aggregation, ATP/ADP release and TXA2 production. PAM caused reductions in platelet responses to AA, ADP, collagen, EPI, TRAP-6 and U46619, whilst aspirin inhibited responses to AA, collagen and EPI. We conclude that the optimul method offers a viable, standardised approach, allowing platelet reactivity testing and could provide a broad platelet function analysis without the need for dedicated equipment.
Minimum important differences for the patient-specific functional scale, 4 region-specific outcome measures, and the numeric pain rating scale.

STUDY DESIGN Multicenter, prospective, longitudinal cohort study. OBJECTIVES To investigate the minimum important difference (MID) of the Patient-Specific Functional Scale (PSFS), 4 region-specific outcome measures, and the numeric pain rating scale (NPRS) across 3 levels of patient-perceived global rating of change in a clinical setting. BACKGROUND The MID varies depending on the external anchor defining patient-perceived "importance. " The MID for the PSFS has not been established across all body regions. METHODS One thousand seven hundred eight consecutive patients with musculoskeletal disorders were recruited from 5 physical therapy clinics. The PSFS, NPRS, and 4 region-specific outcome measures-the Oswestry Disability Index, Neck Disability Index, Upper Extremity Functional Index, and Lower Extremity Functional Scale-were assessed at the initial and final physical therapy visits. Global rating of change was assessed at the final visit. MID was calculated for the PSFS and NPRS (overall and for each body region), and for each region-specific outcome measure, across 3 levels of change defined by the global rating of change (small, medium, large change) using receiver operating characteristic curve methodology. RESULTS The MID for the PSFS (on a scale from 0 to 10) ranged from 1.3 (small change) to 2.3 (medium change) to 2.7 (large change), and was relatively stable across body regions. MIDs for the NPRS (-1.5 to -3.5), Oswestry Disability Index (-12), Neck Disability Index (-14), Upper Extremity Functional Index (6 to 11), and Lower Extremity Functional Scale (9 to 16) are also reported. CONCLUSION We reported the MID for small, medium, and large patient-perceived change on the PSFS, NPRS, Oswestry Disability Index, Neck Disability Index, Upper Extremity Functional Index, and Lower Extremity Functional Scale for use in clinical practice and research.