Miracle-dz/UniFAR-FTUs huggingface dataset:
An in vitro model of ciprofloxacin and minocycline transport by oral epithelial cells.

BACKGROUND Fluoroquinolones and tetracyclines can penetrate epithelial cells, but the mechanism by which they cross the plasma membrane is unclear. In this study, a cell line derived from oral epithelium was used as a model to demonstrate a role for active transport. METHODS Transport of ciprofloxacin and minocycline by confluent cell monolayers was assayed by measuring the increase in cell-associated fluorescence. RESULTS Uptake of both agents was saturable and was inhibited at low temperatures. At 37 degrees C, the cells transported ciprofloxacin and minocycline with Km values of 351 and 133 microg/ml, respectively, and maximum velocities of 5.11 and 13.4 ng/min/microg cell protein, respectively. When ciprofloxacin and minocycline were removed from the extracellular medium, the intracellular levels of both agents decreased. Ciprofloxacin efflux from loaded cells occurred more rapidly than with minocycline. Cells accumulated intracellular drug levels that were at least 8-fold higher than extracellular levels for ciprofloxacin and at least 40-fold higher for minocycline. Transport of ciprofloxacin and minocycline was significantly influenced by pH and was most favorable at pH 7.7 and 7.2, respectively. While ciprofloxacin transport was Na+ independent, minocycline transport was strongly inhibited when sodium in the medium was replaced with choline. Transport of both agents was inhibited by a variety of organic cations, but the pattern of inhibition was different. Papaverine, phenylephrine, and doxycycline competitively inhibited minocycline transport, but inhibited ciprofloxacin transport by a non-competitive mechanism. CONCLUSIONS Epithelial cells take up ciprofloxacin and minocycline via different active transport systems. These transporters may play an important role in enhancing the effectiveness of these agents against invasive pathogens.
Reducing host load, network load, and latency in a distributed shared memory

Changes made to a distributed shared memory that runs of Sun workstations under SunOS 4.0 operating systems, called Mether, are outlined. Protocols developed to use Mether and that minimize host load, network load, and latency are discussed. The changes to Mether involve exposing an inconsistent store to the applications and making access to the consistent and inconsistent versions very convenient, providing both demand-driven and data-driven semantics for updating pages, and allowing the user to specify that only a small subset of a page needs to be transferred. <<ETX>>
Limited syntactic parallelism in Chinese ambiguity resolution

Using the stop-making-sense paradigm (Boland, Tanenhaus, Garnsey, & Carlsen, 1995) and eye-tracking during reading, we examined the processing of the Chinese Verb NP 1 de NP 2 construction, which is temporarily ambiguous between a complement clause (CC) analysis and a relative clause (RC) analysis. Resolving the ambiguity as the more complex, less preferred CC was costly under some conditions but not under others. We took this as evidence for a limited parallel processor, such as Tabor and Hutchins’ (2004) SOPARSE, that maintains multiple syntactic analyses across several words of a sentence when the structures are each supported by the available constraints.
A global lightning parameterization based on statistical relationships among environmental factors, aerosols, and convective clouds in the TRMM climatology

The objective of this study is to determine the relative contributions of normalized convective available potential energy (NCAPE), cloud condensation nuclei (CCN) concentrations, warm cloud depth (WCD), vertical wind shear (SHEAR), and environmental relative humidity (RH) to the variability of lightning and radar reflectivity within convective features (CFs) observed by the Tropical Rainfall Measuring Mission (TRMM) satellite. Our approach incorporates multidimensional binned representations of observations of CFs and modeled thermodynamics, kinematics, and CCN as inputs to develop approximations for total lightning density (TLD) and the average height of 30 dBZ radar reflectivity (AVGHT30). The results suggest that TLD and AVGHT30 increase with increasing NCAPE, increasing CCN, decreasing WCD, increasing SHEAR, and decreasing RH. Multiple‐linear approximations for lightning and radar quantities using the aforementioned predictors account for significant portions of the variance in the binned data set (R2 ≈ 0.69–0.81). The standardized weights attributed to CCN, NCAPE, and WCD are largest, the standardized weight of RH varies relative to other predictors, while the standardized weight for SHEAR is comparatively small. We investigate these statistical relationships for collections of CFs within various geographic areas and compare the aerosol (CCN) and thermodynamic (NCAPE and WCD) contributions to variations in the CF population in a partial sensitivity analysis based on multiple‐linear regression approximations computed herein. A global lightning parameterization is developed; the average difference between predicted and observed TLD decreases from +21.6 to +11.6% when using a hybrid approach to combine separate approximations over continents and oceans, thus highlighting the need for regionally targeted investigations in the future.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Continuous Renal Replacement Therapies in Patients with Liver Disease

Patients with acute and chronic liver disease are prone to hypotension, and mortality increases when acute kidney injury supervenes. Hypotension during renal replacement therapy compromises cerebral perfusion, which can exacerbate cerebral edema in cases of fulminant hepatic failure and those with encephalopathy due to chronic liver failure. As such, any renal replacement therapy utilized should have minimal adverse effects on cardiovascular and cerebrovascular stability. Continuous modes of renal replacement therapy have been shown to cause less cardiovascular and cerebrovascular instability compared to other modalities, and as such are the treatments of choice for this group of critically ill patients.
Diagnosing Major Depressive Disorder V: Applying the DSM-IV Exclusion Criteria in Clinical Practice

To be diagnosed with DSM-IV major depressive disorder (MDD), a patient must meet five out of nine symptom criteria, one of which is depressed mood or pervasive loss of interest or pleasure. Once a patient has reached this symptom threshold, there are several exclusionary criteria that need to be passed to receive the diagnosis. The symptoms must cause significant distress or impairment in functioning, the symptoms cannot be caused by substance use or a general medical condition, and the symptoms cannot be better accounted for by bereavement. Finally, the presence of psychotic symptoms not coincident with the depressive symptoms excludes the diagnosis. We are not aware of any studies of psychiatric patients that have examined the impact of all of these exclusionary rules on the diagnosis of MDD in clinical practice. It is important for clinicians to know how often each of these factors might exclude the diagnosis of MDD so that they can be more or less vigilant to their presence. The goal of the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project was to examine the impact of the DSM-IV exclusion rules on the diagnosis of MDD. In total, 38 (3.0%) of the 947 patients meeting the DSM-IV symptom inclusion criteria were excluded from a diagnosis of MDD or bipolar depression. These results suggest that the DSM-IV exclusion criteria for MDD had only a modest impact on diagnosis in psychiatric outpatients. It is likely that the results of a study of the impact of the DSM-IV depression exclusion criteria will depend on where the study is conducted. The potential influence of different settings on diagnostic exclusion is discussed.
The Safety of and Indications for Immediate Reconstruction of Head and Neck Melanoma Defects: Our Early Experience

AbstractMelanoma excision requires wide margins, leaving large defects. Surgical dogma has taught that definitive reconstruction of melanoma defects be performed after permanent pathology results, with skin grafts favored. However, this results in an open wound and the need for a second operation. The advantages of immediate reconstruction with flaps are single-stage surgery, high patient satisfaction, no period of disfigurement, and cost savings. Our purpose was to evaluate rate of positive margins and local recurrence after immediate reconstruction of head and neck melanoma (HNM) defects with flaps to determine safety of this approach.We prospectively followed all patients with HNM treated at a single center from January 2010 to June 2012 and collected patient and tumor data and reconstruction type. Outcomes assessed were permanent pathology margins and local recurrence rate. Risk factors for positive margins were assessed.Seventy-six patients with HNM were treated with wide excision and immediate flap reconstruction with a mean age of 59 years. Five patients had melanoma in situ and 71 had invasive melanoma. There was a 15.4% ulceration rate. Median thickness for invasive melanoma was 2.2 mm. Mean excision margin was 1.4 cm. Median follow-up was 2 years; 5.3% of patients had positive margins on permanent pathology after reconstruction and 3 were reexcised with negative margins. Local recurrence rate was 2.6% with no recurrence in patients with previous reexcised positive margins. Significant risk factors for positive margins were melanoma in situ excised with 5-mm margins (P = 0.012) and desmoplastic melanoma (P < 0.02). Immediate flap reconstruction after excision of HNM can be safely performed with low positive margin and local recurrence rates. This should be offered to patients, especially those with primary melanomas with distinct borders and excision margins greater than or equal to 1 cm.
Influence of latent risk factors on job satisfaction, job stress and intention to leave in anaesthesia teams: A cross-sectional survey

CONTEXT Current thinking about patient safety emphasises the causal relationship between working conditions, referred to as latent risk factors (LRFs), and the quality of clinical care. OBJECTIVE To investigate the extent to which LRFs are related to job satisfaction, job stress and intention to leave for specialist anaesthetists, trainee anaesthetists and nurse anaesthetists. We expected the different members of the anaesthesia team to show differing perceptions of LRFs, and differences in predictive LRFs for well-being. DESIGN Cross-sectional survey. SETTING Three university hospitals in the Netherlands. PARTICIPANTS One hundred and nine specialist anaesthetists, 46 trainee anaesthetists and 115 nurse anaesthetists. OUTCOME MEASURES LRFs were measured as independent variables. Job satisfaction, job stress and intention to leave were measured as dependent variables. The differences between groups on LRFs, job satisfaction, job stress and intention to leave were analysed using one-way analysis of variance. The contribution of outcomes and LRFs were tested by regression analyses. RESULTS The overall response rate was 62%. More than 60% of the professionals reported unfavourably on access to information and quality of procedures. Nurse anaesthetists reported more problems for every LRF than specialist anaesthetists and trainee anaesthetists. LRFs accounted for a significant proportion of variance in job satisfaction: 63% in specialist anaesthetists, 55% in trainee anaesthetists and 42% in nurse anaesthetists. LRFs also explained important parts of the variance in intention to leave in specialist anaesthetists (41%) and nurse anaesthetists (21%). LRFs accounted for a significant proportion of variance in stress: 25% in specialist anaesthetists and 22% in nurse anaesthetists. Only working hours was a predictor of stress in trainee anaesthetists (22%). CONCLUSION LRFs are important correlates of the well-being of anaesthesia staff. Important differences between the different members of the anaesthesia team emerged in the set of LRFs that affect their well-being. These differences should be taken into account both in research and intervention projects.
Observation of Esaki-Tsu negative differential velocity in GaAs/AlAs superlattices.

The perpendicular peak velocity and critical field have been measured in a series of GaAs/AlAs superlattices as a function of the miniband width and miniband position relative to the AlAs X confined levels. The data cannot be explained by the electric-field localization mechanism [R. Tsu and G. D\"ohler, Phys. Rev. B 12, 680 (1975)] in the range of superlattice parameters investigated, but is qualitatively understood in terms of electron acceleration within the miniband [L. Esaki and R. Tsu, IBM J. Res. Develop. 14, 61 (1970)].
Critical Roles for Both STAT1-Dependent and STAT1-Independent Pathways in the Control of Primary Dengue Virus Infection in Mice1

Dengue virus (DEN), a flavivirus, causes dengue fever and dengue hemorrhagic fever/dengue shock syndrome, the most common mosquito-borne viral illnesses in humans worldwide. In this study, using STAT1−/− mice bearing two different mutant stat1 alleles in the 129/Sv/Ev background, we demonstrate that IFNR-dependent control of primary DEN infection involves both STAT1-dependent and STAT1-independent mechanisms. The STAT1 pathway is necessary for clearing the initial viral load, whereas the STAT1-independent pathway controls later viral burden and prevents DEN disease in mice. The STAT1-independent responses in mice with primary DEN infection included the early activation of B and NK cells as well as the up-regulation of MHC class I molecules on macrophages and dendritic cells. Infection of bone marrow-derived dendritic cell cultures with either DEN or Sindbis virus, another positive-strand RNA virus, confirmed the early vs late natures of the STAT1-dependent and STAT1-independent pathways. Collectively, these data begin to define the nature of the STAT1-dependent vs the STAT1-independent pathway in vivo.
Ultrasound-Guided Nerve Block for Inguinal Hernia Repair: A Randomized, Controlled, Double-Blind Study

Background and Objectives Open inguinal hernia repair in adults is considered a minor surgical procedure but can be associated with significant pain. We aimed to evaluate acute postoperative pain management in male adults randomized to receive an ultrasound-guided ilioinguinal and iliohypogastric nerve block administered before surgery, in addition to a standard analgesic regimen. Methods Sixty patients were included in this randomized, controlled, and double-blind study. Patients were randomized to the administration of a block with 20 mL bupivacaine 0.5% or a placebo block with 20 mL saline. The primary outcome measure was pain at mobilization in the postanesthesia care unit (PACU). Pain at rest, dermatomal anesthesia, time spent in the PACU/ward, opioid consumption, postoperative vomiting and nausea, ability to perform activities of daily living, and perceived ill health status were secondary outcomes. Results A significant reduction in pain scores at mobilization (P<0.001) and rest (P < 0.005) was recorded in the bupivacaine group upon arrival in the PACU and again after 30 minutes. Pain at rest was similarly reduced in the bupivacaine group at the time of discharge (P < 0.017). There were significantly fewer patients (P < 0.05) with severe (numerical rating scale >5) and moderate (numerical rating scale >3) pain at mobilization and rest, respectively. Opioid consumption and time spent in the PACU were not significantly different between groups. Conclusions Ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerves resulted in a statistically significant and clinically relevant reduction in postoperative pain in the PACU both at mobilization and at rest.
Does stress exacerbate liver diseases?

Although anecdotal comments on detrimental effects of psychosocial stress on liver diseases can be found even in the early literature, only recently has scientific evidence been reported. The present article reviewed such evidence to demonstrate how stress exacerbates liver diseases. A search of the literature from the last two decades was performed using MEDLINE by pairing ‘psychological stress’ with ‘liver’ or ‘hepatitis. ’ Additional research was conducted by screening the bibliographies of articles retrieved in the MEDLINE search. The search results showed that the principal effectors of the activated hypothalamic–pituitary–adrenal (HPA) axis, glucocorticoids, can exert a facilitative effect on the hepatic inflammatory response and even increase the risk of developing hepatocellular carcinoma. For certain liver diseases, defective HPA axis activation, which probably contributed to the exacerbation of the liver disease, has been reported. The efferent sympathetic/adrenomedullary system mainly contributes to the stress‐induced exacerbation of liver diseases via its neurotransmitters, the catecholamines. In contrast, the efferent parasympathetic nervous system elicits an inhibitory effect on the development of hepatic inflammation. In conclusion, the pathophysiological interaction between stress and the liver appears to be regulated by the complex, dynamic networks of both the endocrine and autonomic nervous systems, which implies a further need for basic research into the involved mechanisms and for clinical evidence to apply psychosocial support to patients with chronic liver diseases.
HISTOPATHOLOGICAL CHANGES IN CILIARY GANGLION OF RABBITS WITH SUBARACHNOID HEMORRHAGE

The histopathological changes in the ciliary ganglia due to subarachnoid hemorrhage were investigated. Subarachnoid hemorrhage was produced by infusing autologous blood to the cisterna magna of rabbits. The number of neurons in the ganglia was evaluated with physical dissector method. Comparing with controls, a statistically significant increase in the number of degenerated neurons in subarachnoid hemorrhage group was noted. It is considered that the loss of trophic effect from the presynaptic supply of ciliary ganglion via the preganglionic fibers of oculomotor nerve could alter the structure of the ganglion through the anterograde transneuronal degeneration process in subarachnoid hemorrhage.
B‐cell lymphoma, unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and burkitt lymphoma: study of 39 cases

B‐cell lymphoma, unclassifiable (B‐UCL), with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma, is a poorly characterized entity. Therefore, we investigated cases of B‐UCL treated by the Nebraska Lymphoma Study Group (NLSG). We searched the NLSG registry for years 1985–2010 for cases of B‐UCL. Immunohistochemical stains and fluorescence in situ hybridization studies for MYC, BCL2 and BCL6 gene rearrangements were performed. Among the 39 cases studied, 54% were male and 46% were female, with a median age of 69 years. The majority of patients presented with advanced‐stage disease (62%) and had high (3–5) International Prognostic Index (IPI) scores (54%). The median overall survival (OS) was only 9 months and the 5‐year OS was 30%. Patients with low IPI scores (0–2) had a better survival than those with high scores (3–5). The cases were genetically heterogeneous and included 11 ‘double‐hit’ lymphomas with rearrangements of both MYC and BCL2 or BCL6. None of the immunohistochemical or genetic features was predictive of survival. This B‐cell lymphoma is a morphologically‐recognizable entity with a spectrum of genetic abnormalities. New and better treatments are needed for this aggressive lymphoma.
The relationship between behavioural inhibition, anxiety disorders, depression and CD4 counts in HIV-positive adults: a cross-sectional controlled study

Abstract This study examined the relationships between behavioural inhibition (BI), anxiety disorders, depression and CD4 counts in 456 HIV-infected adults attending primary healthcare HIV clinics in South Africa. Our first hypothesis was that BI would be positively correlated with anxiety disorders and with depression. Our second hypothesis was that BI, anxiety disorders and depression would be negatively correlated with CD4 counts. Participants completed the Retrospective Self-Report of Childhood Inhibition scale (RSRCI), the Center for Epidemiologic Studies Depression scale (CES-D) and the Mini-International Neuropsychiatric Interview (MINI). We found that BI was positively correlated with depression, agoraphobia, social phobia (social anxiety disorder) and posttraumatic stress disorder (PTSD). In addition, we found that BI, anxiety disorders and depression were not associated with CD4 counts. Finally, we found no gender effects for BI, depression, CD4 counts or any anxiety disorder diagnosis. While BI was linked to certain anxiety disorders, we found no evidence to suggest that BI, a diagnosis of an anxiety disorder, and/or depressive symptoms were associated with CD4 counts among HIV-positive adults.
Assessing the economics of vaccination for Neisseria meningitidis in industrialized nations: A review and recommendations for further research

Objectives: To review the existing health economic literature on meningococcal disease vaccination. Methods: A Medline search for economic evaluations of vaccination programs for meningococcal disease in developed countries was conducted. All identified studies were reviewed. Results: Nine published studies were identified examining either mass vaccination during outbreaks or routine vaccination. Although net expenses were estimated in almost all studies, the resulting cost-effectiveness ratios varied widely. Vaccination of college-age students was found to be potentially cost-effective in Australia but not in the United States. With one exception, routine vaccination of children and adolescents in Europe was predicted to be cost-effective. Many simplifying assumptions were made, and important elements were often left out, in particular the potential for reduced transmission of disease. Conclusions: The methods used and the vaccination strategies vary widely, and results do not provide strong grounds for making conclusions as to whether vaccination is cost-effective. Furthermore, in all instances, transmission of disease, changes in population carriage rates, and outbreaks are either ignored, dealt with using very broad simplifying assumptions, or are not necessarily generalizable to other settings. The analyses provide some insight into the potential cost-effectiveness of vaccination, but more importantly, they highlight areas requiring further study. Economic evaluations based on observed outcomes from recently implemented strategies would be helpful, as would more sophisticated health economic models. The choice of vaccination strategies cannot be based on the results of existing economic analyses.