Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of midazolam and flumazenil in urology

The effects of midazolam (3–10 mg im.) and their reversal by flumazenil were studied in transurethral endoscopic procedures performed using topical analgesia. In one randomised study, patients (n = 84) received either no medication or flumazenil (0.5 mg i.v.) on completion of endoscopy. Recovery was assessed subjectively. Within 15 min, 83% of those receiving flumazenil were considered ready for discharge compared with only 24% of the control group (P<0.001). In a second randomised, double‐blind, placebo‐controlled trial of 44 patients, post‐operative recovery was assessed using five objective psychomotor tests. Whereas the placebo group took up to 2 h to recover, those receiving flumazenil recovered fully or returned to near control values within 15 min. Sedoanalgesia ‐ a technique combining adequate local anaesthesia with sedation (using midazolam) ‐ has wide application in urology, and the introduction of flumazenil has major implications for the practice of day‐case surgery.
Correlation Between Visual Function and Photoreceptor Integrity in Diabetic Macular Edema: Spectral-Domain Optical Coherence Tomography

Abstract Purpose: To evaluate the relationship between visual function and (i) microstructural changes in the fovea of the inner segment-outer segment junction (IS/OS) and (ii) external limiting membrane (ELM) in diabetic macular edema (DME). Methods: We conducted a retrospective, observational, cross-sectional study of 40 DME patients (61 eyes), all of whom had been treated at Shanghai First People’s Hospital. Patients were divided into groups based on integrity of the IS/OS or ELM: IS/OS (+, ± and −) and ELM (+, ± and −). We performed best-corrected visual acuity (BCVA), MP1 microperimetry and spectral-domain optical coherence tomography (SD-OCT) on all patients. Several variables, including IS/OS and ELM integrity, central macular thickness (CMT) and central macular volume (CMV), were evaluated by two observers, each masked to patients’ BCVA. Main outcome measures included determination of the association of visual function with SD-OCT results. Results: Significant differences were found between IS/OS (+), IS/OS (±) and IS/OS (−) groups in BCVA (66.88 ± 7.89, 51.60 ± 9.39, 32.64 ± 17.93 letters, p < 0.001); macular sensitivity (MS; 8.21 ± 2.91, 3.55 ± 2.75, 2.72 ± 1.86 dB, p < 0.001); fixation stability within 2° (82.09 ± 12.76, 66.43 ± 29.54, 33.73 ± 29.51%, p < 0.001); and % central fixation (74.87 ± 16.88, 61.39 ± 31.38, 31.64 ± 31.89%, p < 0.001); but no differences were found for CMT (p = 0.069) or CMV (p = 0.069). Results were similar for ELM groups. There were significant differences between ELM (+), ELM (±) and ELM (−) groups in BCVA (64.16 ± 9.49, 50.44 ± 9.83, 32.73 ± 17.98 letters, p < 0.001); MS (7.54 ± 3.22, 3.38 ± 2.38, 2.20 ± 1.72 dB, p < 0.001); fixation stability within 2° (81.48 ± 15.26, 61.12 ± 31.63, 35.00 ± 29.07%, p < 0.001); and % central fixation (75.90 ± 17.33, 55.88 ± 30.94, 30.09 ± 33.00%, p < 0.001); but not for CMT (p = 0.216) or CMV (p = 0.202). There was a strong correlation (r = 0.881, p < 0.001) between ELM and IS/OS integrity for the same patient. Categories of IS/OS showed more severe changes than did those of ELM. Conclusions: Both IS/OS and ELM integrity correlated positively with visual function in DME patients. Further studies are needed to confirm and validate this relationship.
Cutting Edge: Functional Role for Proline-Rich Tyrosine Kinase 2 in NK Cell-Mediated Natural Cytotoxicity1

Protein tyrosine kinase activation is one of the first biochemical events in the signaling pathway leading to activation of NK cell cytolytic machinery. Here we investigated whether proline-rich tyrosine kinase 2 (Pyk2), the nonreceptor protein tyrosine kinase belonging to the focal adhesion kinase family, could play a role in NK cell-mediated cytotoxicity. Our results demonstrate that binding of NK cells to sensitive target cells or ligation of β2 integrins results in a rapid induction of Pyk2 phosphorylation and activation. By contrast, no detectable Pyk2 tyrosine phosphorylation is found upon CD16 stimulation mediated by either mAb or interaction with Ab-coated P815 cells. A functional role for Pyk2 in natural but not Ab-mediated cytotoxicity was demonstrated by the use of recombinant vaccinia viruses encoding the kinase dead mutant of Pyk2. Finally, we provide evidence that Pyk2 is involved in the β2 integrin-triggered extracellular signal-regulated kinase activation, supporting the hypothesis that Pyk2 plays a role in the natural cytotoxicity by controlling extracellular signal-regulated kinase activation.
Meat goat performance and carcass parameters when finished on orchardgrass, red clover, or alfalfa pastures

The meat goat industry is growing rapidly in the U.S., particularly on small farms. There are a diversity of forage types and qualities used in meat goat production systems. Seventy-two Boer goats were used to evaluate weight gain and carcass parameters when growing goats were finished on alfalfa (Medicago sativa L.; ALF), red clover ( Trfolium pratense L.; RCL), or orchardgrass (Dactylis glomerata L.; OGR) pastures without energy supplementation. Forage mass showed an interaction (P <0.001) between treatment and time over the grazing season. Goat kids grazing RCL and ALF had higher BW than those grazing OGR throughout the grazing season. Average daily gain (ADG) was similar for ALF and RCL kids (mean 0.18 lb/d) and both were greater (P < 0.001) than OGR (0.11 lb/d). Carcass wt were similar for kids finished on RCL and ALF (mean 33.8 lb), but both were greater (P <0.0001) than kids grazing OGR (29.8 lb). Dressing percentage of RCL and OGR was similar (mean 51.7 %), but both were greater (P <0.05) than ALF (49.8 %). Ribeye area was higher (P < 0.01) for kids finished on RC compared to ALF and OGR. Backfat measurements were not different (mean 0.05 in). Goats finished on ALF, RCL, and OGR produced desirable finished BW and carcasses for the Muslim Halal ethnic market. Introduction: The meat goat industry is growing rapidly in the U.S., particularly on small farms. Meat goat production in the U.S. almost extensively uses the Boer breed to take advantage of the meat-type conformation and heterosis derived from crossbreeding. Weight gains of over 200 g/d for Boer and Boer crossbreeds have been reported (McGregor, 1985). However, using simulation modeling, Blackburn (1995) reported that as the forage base (quality and quantity) changed from high forage to low forage, Boer goat performance ranked below the Spanish goat, suggesting that nutrient intake from lowto medium-quality grasses is insufficient to maximize growth potential for Boer and Boer-cross goats. Alfalfa ((Medicago sativa L.; ALF) is an important legume forage for many classes of livestock (Van Keuren and Matches, 1988) and ALF hay is often used to supply crude protein in finishing diets for small ruminants. Alfalfa is a tall growing, winter hardy plant that produces high yields and quality forage (Hoveland, 1992) and supports superior weight gains (Gelaye et al., 1990) in goat systems. Red clover (Trifoliumpratense L.; RCL) grows 'Supervisory Research Animal Scientist and Research Agronomist, respectively, USDA, ARS, Appalachian Farming Systems Research Center, 1224 Airport Road, Beaver, WV 25813-9423; Program Specialist, West Virginia University, Dept. Animal and Veterinary Sciences, Morgantown, WV 26506.
A quantitative interpretation of IVIM measurements of vascular perfusion in the rat brain

Pulsed gradient spin echo (PGSE) sequences have been used to measure the signal loss of 19F in perfluorinated hydrocarbon blood substitutes moving within the vasculature of the rat brain in the experimental conditions of the study. The signal loss is not characterized by a single apparent pseudodiffusion coefficient. A simple vascular network model based on self‐similarity hss been used to calculate the shape of the signal loss. Excellent agreement with the experiment has been obtained showing that the IVlM measurements are sensitive to flow over a wide range of vessel diameters and flow rates. This model of vascular structure may serve well for other MR measurements that are sensitive to perfusion.
Effects of Age at Implantation in Young Children

This study examined the effects of age at implantation on the development of communication abilities in children with early implantation. The 73 participants were prelingually deafened, received a cochlear implant before 5 years of age, and used current cochlear implant technology. The children were administered a battery of speech and language outcome measures before implantation and again at successive 6-month postimplant intervals. A mixed model analysis was used to examine the rate of growth in word recognition and language skills as a function of age at time of implantation. The results revealed significant improvements in communication skills over time. Spoken word recognition improved at a faster rate in the oral children with early implantation. However, the children who underwent implantation before 3 years of age had significantly faster rates of language development than did the children with later implantation. The oral children demonstrated more rapid gains in communication abilities than did the children who used total communication.
Atmospheric Acid Gases in Tokushima, Japan, Monitored with Parallel Plate Wet Denuder Coupled Ion Chromatograph

During the summer of 2011 and winter of 2012, we continuously measured trace acid gas concentrations in Tokushima, Japan, using a parallel plate wet denuder coupled ion chromatograph. The average concentrations of hydrochloric acid (HCl), nitrous acid (HONO), nitric acid (HNO_3), and sulfur dioxide (SO_2) were, respectively, 0.54, 1.20, 1.17, and 3.22 μg m^−3 in the summer, and 0.09, 1.06, 0.46, and 5.11 μg m^−3 in the winter. In the summer, concentrations of all the acid gases increased after sunrise and showed a strong diurnal pattern with daytime maxima and nighttime minima, but the time at which concentration levels began to increase and the pace of increase differed among the acid gases. The concentration of HONO increased sharply immediately after sunrise, while concentrations of the other three gases began increasing about one and half hours later. SO_2 showed the fastest rate of increase, followed by HNO_3 and HCl. These differences were likely attributable to the formation processes of gaseous substances.
Induction of neutral trehalase Nth1 by heat and osmotic stress is controlled by STRE elements and Msn2/Msn4 transcription factors: variations of PKA effect during stress and growth

Saccharomyces cerevisiae neutral trehalase, encoded by NTH1, controls trehalose hydrolysis in response to multiple stress conditions, including nutrient limitation. The presence of three stress responsive elements (STREs, CCCCT) in the NTH1 promoter suggested that the transcriptional activator proteins Msn2 and Msn4, as well as the cAMP‐dependent protein kinase (PKA), control the stress‐induced expression of Nth1. Here, we give direct evidence that Msn2/Msn4 and the STREs control the heat‐, osmotic stress‐ and diauxic shift‐dependent induction of Nth1. Disruption of MSN2 and MSN4 abolishes or significantly reduces the heat‐ and NaCl‐induced increases in Nth1 activity and transcription. Stress‐induced increases in activity of a lacZ reporter gene put under control of the NTH1 promoter is nearly absent in the double mutant. In all instances, basal expression is also reduced by about 50%. The trehalose concentration in the msn2 msn4 double mutant increases less during heat stress and drops more slowly during recovery than in wild‐type cells. This shows that Msn2/Msn4‐controlled expression of enzymes of trehalose synthesis and hydrolysis help to maintain trehalose concentration during stress. However, the Msn2/Msn4‐independent mechanism exists for heat control of trehalose metabolism. Site‐directed mutagenesis of the three STREs (CCCCT changed to CATCT) in NTH1 promoter fused to a reporter gene indicates that the relative proximity of STREs to each other is important for the function of NTH1. Elimination of the three STREs abolishes the stress‐induced responses and reduces basal expression by 30%. Contrary to most STRE‐regulated genes, the PKA effect on the induction of NTH1 by heat and sodium chloride is variable. During diauxic growth, NTH1 promoter‐controlled reporter activity strongly increases, as opposed to the previously observed decrease in Nth1 activity, suggesting a tight but opposite control of the enzyme at the transcriptional and post‐translational levels. Apparently, inactive trehalase is accumulated concomitant with the accumulation of trehalose. These results might help to elucidate the general connection between control by STREs, Msn2/Msn4 and PKA and, in particular, how these components play a role in control of trehalose metabolism.
SURVEY OF THE TRADITIONAL POULTRY PRODUCTION SYSTEM IN THE BAMENDA AREA , CAMEROON

SURVEY OF THE TRADITIONAL POULTRY PRODUCTION SYSTEM IN THE BAMENDA AREA, CAMEROON. A study of the traditional poultry production system in the Bamenda area in Cameroon was conducted using a baseline survey covering the rainy and dry seasons from December, 1999–June, 2000. This survey focused mainly on the characterization of the flock size and structure, housing system, feeding, marketing of chickens, health, flock breeding and ownership patterns. The results showed that among poultry species surveyed, chickens predominated in all households, followed by ducks (15.4%) and pigeons (7.7%). A cock had access to about 2–3 hens and one hen had a brood of 1–3 chicks at a time with an overall higher hen/cock and chicks/hen ratio for the dry season. Production and reproduction performance results showed that hens laid about 3 clutches of 12 eggs per year and this was similar for both seasons. The most predominant disease symptoms in descending order of importance included diarrhoea, coughing and ectoparasitism. Although the overall disease occurrence rate was high in growers, chicks suffered from many unclassified ailments. From the survey results, ethno-veterinary therapy featured as the most frequent method of treating diseases in rural poultry in the Bamenda area. With regard to flock ownership and management patterns, the survey results showed that women owned birds in the majority of the cases (38.5%) followed by men (23.1%) and children (15.3%). Although all gender categories were involved in village chicken management, the greatest participation came from women, followed by men, children and the family as a whole. Construction of shelters was mainly a job for the men with assistance from the children. Women were mostly involved in providing water to the birds, preparing supplementation rations and selling eggs. Finally, with regard to household decision making on issues related to poultry management, men played the leading role (66.7%), followed by women (28.4%) and then children (3.7%).
A Role for KH Domain Proteins (Sam68-like Mammalian Proteins and Quaking Proteins) in the Post-transcriptional Regulation of HIV Replication*

Overexpression of Sam68 functionally substitutes for, as well as synergizes with, human immunodeficiency virus type 1 (HIV-1) Rev in RRE (Rev response element)-mediated gene expression and virus replication. In addition, COOH-terminal deletion and/or point mutants of Sam68 exhibit a transdominant negative phenotype for HIV replication. Sam68 is a member of KH domain family that includes SLM-1, SLM-2 (Sam68 like mammalian); and QKI-5, QKI-6, and QKI-7 (mouse quaking) proteins. The objective of this study was to examine the effects of these KH family proteins on RRE- and CTE (constitutive transportelement of type-D retrovirus)-mediated transactivation. We now report that SLM-1 and SLM-2 proteins, which are the closest relatives of Sam68, marginally enhanced RRE-mediated transactivation, while QK isoforms that are distant relatives of Sam68 had no effect. Interestingly, these proteins still enhanced the effect of Rev in RRE-mediated gene expression. The increase in chloramphenicol acetyltransferase activity was also reflected at the levels of cytoplasmic RRE-chloramphenicol acetyltransferase mRNAs, indicating that Sam68 and KH proteins may have been involved in the stability or export of unspliced RNA. The increase in Rev activity was sensitive to leptomycin B, but not to olomoucine, indicating that the effect of SLM-1, SLM-2, QKI-5, QKI-6, and QKI-7 is exerted through a CRM-1-dependent mRNA export pathway. Thus, KH family proteins play an important role in the post-transcriptional regulation of HIV.
Morphology enabled dipole inversion (MEDI) from a single‐angle acquisition: Comparison with COSMOS in human brain imaging

Magnetic susceptibility varies among brain structures and provides insights into the chemical and molecular composition of brain tissues. However, the determination of an arbitrary susceptibility distribution from the measured MR signal phase is a challenging, ill‐conditioned inverse problem. Although a previous method named calculation of susceptibility through multiple orientation sampling (COSMOS) has solved this inverse problem both theoretically and experimentally using multiple angle acquisitions, it is often impractical to carry out on human subjects. Recently, the feasibility of calculating the brain susceptibility distribution from a single‐angle acquisition was demonstrated using morphology enabled dipole inversion (MEDI). In this study, we further improved the original MEDI method by sparsifying the edges in the quantitative susceptibility map that do not have a corresponding edge in the magnitude image. Quantitative susceptibility maps generated by the improved MEDI were compared qualitatively and quantitatively with those generated by calculation of susceptibility through multiple orientation sampling. The results show a high degree of agreement between MEDI and calculation of susceptibility through multiple orientation sampling, and the practicality of MEDI allows many potential clinical applications. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Systemic Lupus Erythematosus, Osteoporosis, and Fractures

Osteoporosis is a common yet less-recognized complication of systemic lupus erythematosus (SLE) that has been brought to our attention by Zhu, et al ’s article in this issue of The Journal 1. Recent studies, however, have highlighted the high prevalence of fractures in a relatively young population of women suffering from SLE1,2,3,4,5,6,7. There have been many studies reporting different results. This might be explained by the complex relationship between SLE, complications of the disease itself or its treatment, duration of disease, bone loss, and fractures. Indeed the systemic inflammation associated with SLE and the resultant end-organ damage may all play a role1,2,3. Combine this with the traditional risk factors for fracture and it is easy to understand why the study of osteoporosis and fractures in SLE is complex. Confounders include active inflammation and treatment of inflammation with glucocorticoids1,2,3, menopausal status, and disease-associated complications such as renal bone disease and neuropsychiatric disease3. Other non-SLE risk factors including age, medications such as selective serotonin receptor inhibitors (SSRI) and possibly proton pump inhibitors (PPI) may all confound the relationship between SLE and fractures. The effect of treatment with bone-active drugs to prevent bone loss and fractures must also be taken into consideration in studies of SLE. ### Inflammation There is … Address correspondence to Dr. Adachi, St. Joseph’s Hospital, 501-25 Charlton Ave. East, Hamilton, Ontario L8N 1Y2, Canada. E-mail: jd.adachi{at}sympatico.ca
Cytokine Dysregulation, Inflammation and Well-Being

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic ‘overshooting’ with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-α and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the ‘systemic anti-inflammatory feedback’ and/or ‘hyperactivity’ of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
Penicillin-binding proteins in Proteus species

Penicillin-binding proteins in three species of Proteus, Proteus mirabilis, P. morganii, and P. rettgeri, were investigated by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. Penicillin-binding proteins in these Proteus species were compared with those in Escherichia coli K-12. An approximate correlation between penicillin-binding proteins in E. coli and those in Proteus species was shown by several criteria: electrophoretic mobilities; affinities of several beta-lactam antibiotics which show characteristic patterns of binding to penicillin-binding proteins in E. coli; relation between affinities of antibiotics to the proteins and effects on morphological changes in Proteus species; location of beta-lactamase activity among penicillin-binding proteins; and thermostability. The electrophoretic mobilities and several other characteristics of penicillin-binding proteins among the Proteus species examined were found to be similar from species to species and differed only slightly from those of E. coli.
The use of biosensor technology for the engineering of antibodies and enzymes

Recently developed scientific instrumentation featuring surface plasmon resonance detection allows the detection of biomolecular interactions in real time and without chemical modification of the binding partners. These biosensors are proving invaluable tools in protein engineering, particularly in research aimed at the isolation and improvement of protein binders and catalysts from macromolecular repertoires containing billions of individual members. This article reviews the use of biosensor technology for the isolation and characterization of engineered antibodies and enzymes. Copyright © 1999 John Wiley & Sons, Ltd.