Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative evaluation of patient information leaflets by pharmacists, doctors and the general public

This study was undertaken to compare and contrast the views of pharmacists, general practitioners (GPs) and the general public on the value or otherwise of pharmacy‐generated patient information leaflets. All three groups perceived these leaflets to be useful and an aid to improving compliance. Concerning the information included in leaflets, GPs rated the inclusion of a section on side‐effects as being the least important, whilst pharmacists and the general public rated information on the storage of medicines as being least important. Pharmacists' estimates on what percentage of patients actually read leaflets were significantly lower than estimates by the general public. General practitioners and pharmacists generally concurred on the types of patients for whom leaflets are considered unsuitable, although a significantly higher percentage of pharmacists than GPs identified unsuitable patients. There were reservations by the pharmacists concerning the cost‐effectiveness of leaflet facilities and on the value of leaflets compared with verbal counselling. The general public expressed the view that a leaflet facility would affect their choice of pharmacy and that they would be prepared to wait an additional short time to receive such a leaflet. Almost all GPs thought that it was in the patient's best interest to receive an information leaflet.
Morphogenetic mechanisms of epithelial tubulogenesis: MDCK cell polarity is transiently rearranged without loss of cell-cell contact during scatter factor/hepatocyte growth factor-induced tubulogenesis.

Many organ systems are composed of networks of epithelial tubes. Recently, molecules that induce development of epithelial tubules and regulate sites of branching have been identified. However, little is known about the mechanisms regulating cell rearrangements that are necessary for tubule formation. In this study we have used a scatter factor/hepatocyte growth factor-induced model system of MDCK epithelial cell tubulogenesis to analyze the mechanisms of cell rearrangement during tubule development. We examined the dynamics of cell polarity and cell-cell junctions during tubule formation and present evidence for a multistep model of tubulogenesis in which cells rearrange without loss of cell-cell contacts and tubule lumens form de novo. A three-dimensional analysis of markers for apical and basolateral membrane subdomains shows that epithelial cell polarity is transiently lost and subsequently regained during tubulogenesis. Furthermore, components of cell-cell junctional complexes undergo profound rearrangements: E-cadherin is randomly distributed around the cell surface, desmoplakins I/II accumulate intracellularly, and the tight junction protein ZO-1 remains localized at sites of cell-cell contact. This suggests that differential regulation of cell-cell junctions is important for the formation of tubules. Therefore, during tubulogenesis, cell-cell adhesive contacts are differentially regulated while the polarity and specialization of plasma membrane subdomains reorganize, enabling cells to remain in contact as they rearrange into new structures.
Exact performance analysis of hybrid adaptive modulation schemes in multi-channel system

In this paper, we analyze the performance of a multi-channel system with the conventional adaptive modulation (AM) and two hybrid schemes, the adaptive modulation with diversity combining (AMDC) and the adaptive modulation with power loading (AMPL), respectively. In order to achieve higher spectral efficiency and more efficient usage of channel resources under the total transmit power constraint and the required bit error rate (BER), the AMDC jointly uses discrete-rate adaptation and diversity combining scheme, and the AMPL jointly uses discrete-rate adaptation and sub-optimal discrete-power loading. We derive exact closed-form expressions of the performance of a multi-channel system with the conventional adaptive modulation (AM) and these hybrid schemes, in terms of the spectral efficiency, the average BER and the outage probability. We also analyze the impact of imperfect channel estimation on the error performance and validate our analytical results by simulations. Numerical results show that both the AMDC and the AMPL offer higher spectral efficiency than the conventional AM, assuming the perfect channel estimation. However, AMDC offers better performance and reliability than AMPL, under imperfect channel estimation with complex Gaussian error.
Helicobacter pylori Uptake and Efflux: Basis for Intrinsic Susceptibility to Antibiotics In Vitro

ABSTRACT We previously demonstrated (M. M. Exner, P. Doig, T. J. Trust, and R. E. W. Hancock, Infect. Immun. 63:1567–1572, 1995) that Helicobacter pylori has at least one nonspecific porin, HopE, which has a low abundance in the outer membrane but forms large channels. H. pylori is relatively susceptible to most antimicrobial agents but less susceptible to the polycationic antibiotic polymyxin B. We demonstrate here that H. pylori is able to take up higher basal levels of the hydrophobic fluorescent probe 1-N-phenylnaphthylamine (NPN) thanPseudomonas aeruginosa or Escherichia coli, consistent with its enhanced susceptibility to hydrophobic agents. Addition of polymyxin B led to a further increase in NPN uptake, indicative of a self-promoted uptake pathway, but it required a much higher amount of polymyxin B to yield a 50% increase in NPN uptake inH. pylori (6 to 8 μg/ml) than in P. aeruginosa or E. coli (0.3 to 0.5 μg/ml), suggesting that H. pylori has a less efficient self-promoted uptake pathway. Since intrinsic resistance involves the collaboration of restricted outer membrane permeability and secondary defense mechanisms, such as periplasmic β-lactamase (which H. pylori lacks) or efflux, we examined the possible role of efflux in antibiotic susceptibility. We had previously identified in H. pylori 11637 the presence of portions of three genes with homology to potential restriction-nodulation-division (RND) efflux systems. It was confirmed that H. pylori contained only these three putative RND efflux systems, named here hefABC, hefDEF, andhefGHI, and that the hefGHI system was expressed only in vivo while the two other RND systems were expressed both in vivo and in vitro. In uptake studies, there was no observable energy-dependent tetracycline, chloramphenicol, or NPN efflux activity in H. pylori. Independent mutagenesis of the three putative RND efflux operons in the chromosome of H. pylori had no effect on the in vitro susceptibility of H. pylori to 19 antibiotics. These results, in contrast to what is observed inE. coli, P. aeruginosa, and other clinically important gram-negative bacteria, suggest that active efflux does not play a role in the intrinsic resistance of H. pylori to antibiotics.
Spatially varying density dependence drives a shifting mosaic of survival in a recovering apex predator (Canis lupus)

Abstract Understanding landscape patterns in mortality risk is crucial for promoting recovery of threatened and endangered species. Humans affect mortality risk in large carnivores such as wolves (Canis lupus), but spatiotemporally varying density dependence can significantly influence the landscape of survival. This potentially occurs when density varies spatially and risk is unevenly distributed. We quantified spatiotemporal sources of variation in survival rates of gray wolves (C. lupus) during a 21‐year period of population recovery in the Upper Peninsula of Michigan, USA. We focused on mapping risk across time using Cox Proportional Hazards (CPH) models with time‐dependent covariates, thus exploring a shifting mosaic of survival. Extended CPH models and time‐dependent covariates revealed influences of seasonality, density dependence and experience, as well as individual‐level factors and landscape predictors of risk. We used results to predict the shifting landscape of risk at the beginning, middle, and end of the wolf recovery time series. Survival rates varied spatially and declined over time. Long‐term change was density‐dependent, with landscape predictors such as agricultural land cover and edge densities contributing negatively to survival. Survival also varied seasonally and depended on individual experience, sex, and resident versus transient status. The shifting landscape of survival suggested that increasing density contributed to greater potential for human conflict and wolf mortality risk. Long‐term spatial variation in key population vital rates is largely unquantified in many threatened, endangered, and recovering species. Variation in risk may indicate potential for source‐sink population dynamics, especially where individuals preemptively occupy suitable territories, which forces new individuals into riskier habitat types as density increases. We encourage managers to explore relationships between adult survival and localized changes in population density. Density‐dependent risk maps can identify increasing conflict areas or potential habitat sinks which may persist due to high recruitment in adjacent habitats.
Treatment with folic acid ameliorated the histopathological alterations caused by propylthiouracil-induced hypothyroid rat testes

Hypothyroidism is an underactive thyroid gland that cannot make enough thyroid hormone to keep the body running normally. Here we studied the histopathological, immunohistochemical, and ultrastructural changes in the hypothyroid rat testes at the postpubertal stage, in addition to the ameliorating role of folic acid in enhancing spermatogenesis, boosting sperm concentration and building up the antioxidant status against the oxidants. A total of 50 male albino rats were equally divided into 5 groups; the first and second groups comprised the control and folic acid groups, respectively; while the third group comprised the hypothyroid group in which rats received 6-n-propyl-2-thiouracil in drinking water for 6 weeks to induce hypothyroidism. The fourth and fifth groups comprised hypothyroid rats treated with folic acid for 4 weeks and dissected after 6 and 10 weeks, respectively. Testes in the hypothyroid rats showed marked morphological and histological changes in the seminiferous tubules with a reduction in sperm count. Our results indicate that hypothyroidism adversely affects spermatogenesis, suggesting that thyroid hormone might play an important role not only in controlling normal testicular development but also in maintaining normal testicular function and spermatogenesis. Further, we suggested an ameliorating role of folic acid in the relief of testicular tissue from changes due to hypothyroidism. However, we found that the best results were found in cases where folic acid was used as an adjuvant therapy for returning to the euthyroid state.
Algorithm for UWB Pulse Design and its Performance Analysis

Ultra wide band (UWB) is an ideal candidate for achieving high data rates over short distances with low cost and low power consumption. In this paper, we propose a simple pulse design method that uses the iterative combination of five Rayleigh derivatives to meet the FCC UWB indoor spectral mask requirements. The performance comparison between the combination pulse and the second derivative Gaussian pulse is also presented by means of the computer simulation. The simulation results show that the power spectrum density (PSD) of the combination pulse approaches the FCC spectral mask obviously, and the performances of UWB system using combination pulse are better than that using the second derivative Gaussian pulse.
Comparison of serotonin toxicity with concomitant use of either linezolid or comparators and serotonergic agents: an analysis of Phase III and IV randomized clinical trial data.

OBJECTIVES AND METHODS The present study's objective was to evaluate serotonin toxicity with concomitant use of linezolid or comparators and serotonergic agents from 20 Phase III and IV comparator-controlled clinical studies on treatment of various Gram-positive infections. All reported adverse events were evaluated for serotonin toxicity using exact and surrogate terms consistent with Sternbach Criteria and Hunter Serotonin Toxicity Criteria. RESULTS Baseline demographics and co-morbidities were similar between linezolid and comparator groups. No patients in either group were reported to have adverse events identified as serotonin toxicity. Among the patients receiving at least one serotonergic agent, 9 of the 2208 (0.41%) linezolid patients and 3 of the 2057 (0.15%) comparator patients met the Sternbach Criteria [risk ratio (RR) 2.79; 95% confidence interval (95% CI) 0.76-10.31]; 3 (0.14%) of the linezolid patients and 1 (0.05%) of the comparator patients met the Hunter Serotonin Toxicity Criteria (RR 2.79; 95% CI 0.29-26.85). No patients met both criteria. Most patients meeting criteria for serotonin toxicity had past or present co-morbidities that may have contributed to or overlapped with reported adverse events. CONCLUSIONS While the potential exists for serotonin toxicity to occur with concomitant use of linezolid and serotonergic agents, the risk appears to be low. Based on the large database of Phase III and IV studies included in our analysis, we did not find enough evidence to conclude that linezolid-induced serotonin toxicity was different from that of comparators.
Dressings for chronic wounds

Covering wounds, acute and chronic, is one of the most fundamental activities of any medical practitioner. Although wound dressings primarily serve to contain the “good” and keep out the “bad,” research has characterized more specifically the sophisticated interaction between the human wound bed and its dressing counterpart. Wound dressings for today's chronic wounds come in many flavors, ranging from the classic types of moisture‐retentive dressings to silver‐coated varieties to biologic dressings serving as skin substitutes. Moisture‐retentive dressing types include foams, films, hydrogels, hydrocolloids, and alginates. Appropriate use of these dressings can help to keep the wound bed moist, which allows for epithelial migration, angiogenesis, retention of growth factors, autolytic debridement, and maintenance of electrical gradients.
Adaptation of the skeletal muscle calcium-release mechanism to weight-bearing condition.

In the present study, we examined whether weight-bearing condition can regulate the sarcoplasmic reticulum (SR) Ca(2+)-release mechanism. Measurements of alpha 1-subunit dihydropyridine (alpha 1-DHP) and ryanodine receptor levels were made in hypertrophied fast-twitch plantaris muscles 5 wk after surgical removal of synergist muscles (increased weight bearing) and in atrophied slowtwitch soleus muscles (14 days of non-weight bearing) of the rat. Rates of AgNO3-induced SR Ca2+ release were measured with fura 2 as the Ca2+ indicator and pyrophosphate as the precipitating ion during vesicular Ca2+ loading. Ca(2+)-release rates were 38, 49, and 58% lower in vesicles from hypertrophied vs. control muscles at AgNO3 concentrations of 0.05, 0.5, and 5 microM, respectively (control = 18.2 +/- 1.4 microM.mg-1. min-1). Western blots showed no differences in the relative expression of alpha 1-DHP or ryanodine receptor when IIID5 (monoclonal) or GP3 (polyclonal) antibodies were used. There was also no difference in ryanodine (10 nM) binding in Ca(2+)-incubated SR vesicles from hypertrophied muscles, suggesting no difference in the number of channels. In contrast, expression of alpha 1-DHP and ryanodine receptors was increased by 144 and 157% in non-weight-bearing soleus muscles, respectively. Scatchard analysis of DHP binding showed a 40% increase in maximum binding capacity and no change in the dissociation constant with non-weight-bearing muscles. The direction of modification of the SR Ca(2+)-release mechanism is opposite with increased and decreased weight bearing, but the mechanism by which this is achieved appears to be different.
Pleiotropic Effect of a Histidine Kinase on Carbohydrate Metabolism in Synechocystis sp. Strain PCC 6803 and Its Requirement for Heterotrophic Growth

ABSTRACT The deletion of a gene coding for a histidine kinase (sll0750, Hik8) in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 resulted in a conditional lethal phenotype with a pleiotropic effect on the expression of genes involved in glucose metabolism. This mutant had comparable doubling times to wild type (WT) in continuous-light-grown photoautotrophic and mixotrophic cultures, whereas it grew poorly under mixotrophic conditions with different light and dark cycles. Growth was completely stopped, and cells eventually died, when the light duration was less than 6 h on a 24-h regimen. Northern blot analysis demonstrated that steady-state transcript levels of genes encoding key enzymes of glycolysis, gluconeogenesis, the oxidative pentose phosphate pathway, and glycogen metabolism were significantly altered in a strain with mutant hik8 (Δhik8) grown with or without glucose. In some cases, differential expression was dependent on growth conditions (photoautotrophic versus mixotrophic). The enzyme activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and phosphofructokinase were significantly reduced in Δhik8 compared to WT. Glycogen determination indicated that Δhik8 accumulated glycogen under mixotrophic conditions but was unable to utilize these reserves for heterotrophic growth. The results suggest that the loss of gap1 transcription in the absence of Hik8 was the key factor that rendered cells unable to catabolize glucose and grow heterotrophically. Additionally, the transcript levels of the phytochrome gene (cph1) and its cotranscribed response regulator gene (rcp1) were significantly reduced and its dark inducibility was lost in Δhik8. The results demonstrated that Hik8 plays an important role in glucose metabolism and is necessary for heterotrophic growth.
Clinical evaluation of ketamine and lidocaine intravenous infusions to reduce isoflurane requirements in horses under general anaesthesia.

OBJECTIVE To compare isoflurane alone or in combination with systemic ketamine and lidocaine for general anaesthesia in horses. STUDY DESIGN Prospective, randomized, blinded clinical trial. ANIMALS Forty horses (ASA I-III) undergoing elective surgery. METHODS Horses were assigned to receive isoflurane anaesthesia alone (ISO) or with ketamine and lidocaine (LKI). After receiving romifidine, diazepam, and ketamine, the isoflurane end-tidal concentration was set at 1.3% and subsequently adjusted by the anaesthetist (unaware of treatments) to maintain a light plane of surgical anaesthesia. Animals in the LKI group received lidocaine (1.5 mg kg(-1) over 10 minutes, followed by 40 microg kg(-1) minute(-1)) and ketamine (60 microg kg(-1) minute(-1)), both reduced to 65% of the initial dose after 50 minutes, and stopped 15 minutes before the end of anaesthesia. Standard clinical cardiovascular and respiratory parameters were monitored. Recovery quality was scored from one (very good) to five (very poor). Differences between ISO and LKI groups were analysed with a two-sample t-test for parametric data or a Fischer's exact test for proportions (p < 0.05 for significance). Results are mean +/- SD. RESULTS Heart rate was lower (p = 0.001) for LKI (29 +/- 4) than for ISO (34 +/- 6). End-tidal concentrations of isoflurane (ISO: 1.57% +/- 0.22; LKI: 0.97% +/- 0.33), the number of horses requiring thiopental (ISO: 10; LKI: 2) or dobutamine (ISO:8; LKI:3), and dobutamine infusion rates (ISO:0.26 +/- 0.09; LKI:0.18 +/- 0.06 microg kg(-1) minute(-1)) were significantly lower in LKI compared to the ISO group (p < 0.001). No other significant differences were found, including recovery scores. CONCLUSIONS AND CLINICAL RELEVANCE These results support the use of lidocaine and ketamine to improve anaesthetic and cardiovascular stability during isoflurane anaesthesia lasting up to 2 hours in mechanically ventilated horses, with comparable quality of recovery.
Baroreflex sensitivity in the elderly: influence of age, breathing and spectral methods.

Baroreflex sensitivity (BRS) has been proposed as a diagnostic parameter for neurological disorders and as a survival-prognosis parameter in diabetic and cardiac patients. Therefore reference values and the reproducibility of BRS were assessed, taking into account the possible influence of age, gender, test conditions and some analysis variants. Healthy subjects (n=191) were randomly selected from the 50-75-year-old general population (the Hoorn Study). Variations in blood pressure and heart rate were recorded non-invasively during three breathing modes: spontaneous (3 min), slow metronome (1 min; 6 breaths/min=0.1 Hz) and fast metronome (1 min; 15 breaths/min=0.25 Hz), all in a supine position. From these recordings, BRS was assessed as the transfer gain between changes in blood pressure and heart period, and as the alpha coefficient. BRS values ranged from 5.0 to 8.9 ms.mmHg(-1). Slow metronome breathing resulted in higher BRS values than fast breathing, while during spontaneous breathing BRS in the low-frequency band was lower than that in the high-frequency band (respiratory origin). BRS values decreased with lower coherence criteria. BRS-alpha was significantly higher than BRS-gain. While regression analysis showed no gender differences, BRS decreased with age. Therefore age-specific reference values were calculated. The reproducibility of BRS values was in general moderate, with reliability coefficients ranging from 43 to 81% and coefficients of variation ranging from 34 to 59%. In conclusion, this study shows age, breathing mode, frequency and coherence threshold to affect measures of BRS. Therefore these factors should be considered in clinical studies; appropriate reference values are given.
Immunotoxic effects of gold and silver nanoparticles: Inhibition of mitogen-induced proliferative responses and viability of human and murine lymphocytes in vitro

Abstract Understanding the effects of nanoparticles (NP) on immune cell functions is essential in designing safe and effective NP-based in vivo drug delivery systems. The immunomodulatory potential of gold nanoparticles (GNP) and silver nanoparticles (SNP) was investigated in vitro using murine splenic and human peripheral blood lymphocytes (PBL) in terms of effects on viability and mitogen-induced proliferation. Hydrodynamic size and number of NP were characterized using NP tracking analysis (NTA); modal diameters of GNP and SNP were 28 (±1.5) and 66 (± 2.7) nm, respectively, with a unimodal distribution. Lymphocytes were incubated with GNP or SNP in the presence/absence of B- or T-cell mitogens and proliferative responses then determined using [3H]-thymidine incorporation. Concanavalin A (T-cell-specific) and lipopolysaccharide- (B-cell-specific) stimulated responses of murine splenic lymphocytes, as well as phytohemagglutinin (T-cell-specific) and pokeweed mitogen- (B-and T-cell specific) induced responses of human lymphocytes, were significantly inhibited by GNP (25–200 μg/ml) and SNP (12.5–50 μg/ml). However, [3H]-thymidine incorporation by unstimulated lymphocytes was unaffected in the presence of GNP or SNP. Viability of lymphocytes was determined using trypan blue dye exclusion and was significantly inhibited only at 200 μg GNP/ml and 25 or 50 μg SNP/ml. As mitogen responses are most useful to provide supportive mechanistic information on primary immunotoxicologic functional observations, and so far more comprehensive data (in vivo and in vitro) is still needed, the results nevertheless suggest to us that GNP and SNP might potentially be able to modulate immune responses by impacting on lymphocyte activation.
Hyper‐response of OP3 to systemic hyperoxia in the dark‐adapted retina

Purpose: We have demonstrated that the third wavelet (OP3) of the scotopic flash oscillatory potential (OP) complex shows a hyper‐response during experimentally‐induced systemic hyperoxia. The objective of the present study was to further evaluate and detail the time course of this enhanced retinal response.