Miracle-dz/UniFAR-FTUs huggingface dataset:
Low‐dose bupivacaine spinal anaesthesia for percutaneous nephrolithotomy: the suitability and impact of adding intrathecal fentanyl

Background: Unilateral spinal anaesthesia has been used for lower limb surgery with a stable cardiovascular state and a short recovery unit stay. We sought to test the suitability of low‐dose bupivacaine spinal anaesthesia for percutaneous nephrolithotomy, a procedure hitherto performed under general anaesthesia. Furthermore, we hypothesized that adding intrathecal fentanyl to bupivacaine may improve the quality of anaesthesia.
First-line bevacizumab combined with reduced dose interferon-alpha2a is active in patients with metastatic renal cell carcinoma.

BACKGROUND In patients with untreated metastatic renal cell carcinoma (mRCC), progression-free survival (PFS) was longer with bevacizumab + interferon (IFN)-alpha than IFN + placebo (AVOREN trial). In this hypothesis-generating study, subgroup analysis was carried out to determine the effect of IFN dose reduction. PATIENTS AND METHODS A total of 649 patients received IFN 9 MIU s.c. three times weekly plus bevacizumab 10 mg/kg or placebo every 2 weeks until disease progression. The IFN dose was reduced to 6 or 3 MIU with the development of IFN-attributed toxicity. Differences between treatment arms in PFS, response rate and tolerability were analysed in the reduced-dose group. RESULTS IFN dose was reduced in 131 patients in the bevacizumab + IFN arm and 97 patients in the IFN + placebo arm during the trial. PFS rates in the bevacizumab + reduced-dose IFN group were comparable with the total population (Kaplan-Meier estimates of event-free rate at 1 year: 0.524 versus 0.427). Bevacizumab + reduced-dose IFN was well tolerated, with substantial decreases in the rate of adverse events following dose reduction. CONCLUSION This retrospective subgroup analysis suggests that the dose of IFN can be reduced to manage side-effects while maintaining efficacy in patients with mRCC receiving bevacizumab + IFN.
Scanning Electron Microscopic Study of the Dentinal Tubules in Dog Canine Teeth

Dentin adhesive restorative techniques are regularly used in veterinary dentistry. Knowledge of the microanatomic structure and properties of dentin is essential to ensure success in restorative procedures. The aim of this study was to describe the density and diameter of dentinal tubules in dog canine teeth using recently described standardized scanning electron microscopy techniques. The results showed dentin of dog canine teeth to be more oval-shaped with a higher tubular density and slightly larger tubular diameters compared with human teeth. These features suggest dog canine teeth have less intertubular dentin compared with human teeth, which may theoretically result in lower resin-dentin shear bond strengths.
Imaging nanometre‐scale structure in cells using in situ aberration correction

Accurate distance measurements of cellular structures on a length scale relevant to single macromolecules or macromolecular complexes present a major challenge for biological microscopy. In addition to the inherent challenges of overcoming the limits imposed by the diffraction of light, cells themselves are a complex and poorly understood optical environment. We present an extension of the high‐resolution colocalization method to measure three dimensional distances between diffraction‐limited objects using standard widefield fluorescence microscopy. We use this method to demonstrate that in three dimensions, cells intrinsically introduce a large and variable amount of chromatic aberration into optical measurements. We present a means of correcting this aberration in situ [termed ‘Colocalization and In‐situ Correction of Aberration for Distance Analysis’ (CICADA)] by exploiting the fact that there is a linear relationship between the degree of aberration between different wavelengths. By labelling a cellular structure with redundantly multi‐colour labelled antibodies, we can create an intracellular fiducial marker for correcting the individual aberrations between two different wavelengths in the same cells. Our observations demonstrate that with suitable corrections, nanometre scale three‐dimensional distance measurements can be used to probe the substructure of macromolecular complexes within cells.
Is there an increased risk of TB relapse in patients treated with fixed-dose combination drugs in Indonesia?

SETTING South Sulawesi Province, Republic of Indonesia. OBJECTIVE To compare relapse rates among tuberculosis (TB) patients treated with fixed-dose combination drugs (FDCs) and patients treated with the same regimen using loose drugs. METHODOLOGY Between 1999 and 2001, new smear-positive TB patients were randomly allocated to treatment with four-drug FDCs or loose drugs to study differences in treatment outcomes. Although it was not in the original study design, in 2004-2005 we performed a follow-up study by home visit of cured patients. We conducted an interview and tried to collect a sputum sample from each patient. If the patient was absent or had died, a proxy interview was conducted. The sputum samples were examined by microscopy and culture. RESULTS The overall relapse rate was 7.0% in patients who were able to produce a sputum sample. Relapse appeared to be more frequent in the FDC group compared to the loose drug group (10.1% vs. 2.7%, P = 0.074). CONCLUSION This is the first documented long-term follow-up study of patients treated with four-drug FDCs. There is an indication that treatment of new sputum smear-positive TB patients with FDCs provides an increased risk of relapse compared to treatment with loose drugs. The long-term results of treatment with FDCs should be carefully evaluated in other settings.
Social Networks as Contract Enforcement: Evidence from a Lab Experiment in the Field

Lack of well-functioning formal institutions leads to reliance on social networks to enforce informal contracts. Social proximity and network centrality may affect cooperation. To assess the extent to which networks substitute for enforcement, we conducted high-stakes games across 34 Indian villages. We randomized subjects’ partners and whether contracts were enforced to estimate how partners’ relative network position differentially matters across contracting environments. While socially close pairs cooperate even without enforcement, distant pairs do not. Individuals with more central partners behave more cooperatively without enforcement. Capacity for cooperation in the absence of contract enforcement therefore depends on the subjects’ network position. (JEL C93, D86, K12, O15, O17, Z13)
Protein Profiles Associated With Context Fear Conditioning and Their Modulation by Memantine*

Analysis of the molecular basis of learning and memory has revealed details of the roles played by many genes and the proteins they encode. Because most individual studies focus on a small number of proteins, many complexities of the relationships among proteins and their dynamic responses to stimulation are not known. We have used the technique of reverse phase protein arrays (RPPA) to assess the levels of more than 80 proteins/protein modifications in subcellular fractions from hippocampus and cortex of mice trained in Context Fear Conditioning (CFC). Proteins include components of signaling pathways, several encoded by immediate early genes or involved in apoptosis and inflammation, and subunits of glutamate receptors. At one hour after training, levels of more than half the proteins had changed in one or more fractions, among them multiple components of the Mitogen-activated protein kinase, MAPK, and Mechanistic Target of Rapamycin, MTOR, pathways, subunits of glutamate receptors, and the NOTCH pathway modulator, NUMB homolog (Drosophila). Levels of 37 proteins changed in the nuclear fraction of hippocampus alone. Abnormalities in levels of thirteen proteins analyzed have been reported in brains of patients with Alzheimer's Disease. We therefore further investigated the protein profiles of mice treated with memantine, a drug approved for treatment of AD. In hippocampus, memantine alone induced many changes similar to those seen after CFC and altered the levels of seven proteins associated with Alzheimer's Disease abnormalities. Lastly, to further explore the relevance of these datasets, we superimposed responses to CFC and memantine onto components of the long term potentiation pathway, a process subserving learning and memory formation. Fourteen components of the long term potentiation pathway and 26 proteins interacting with components responded to CFC and/or memantine. Together, these datasets provide a novel view of the diversity and complexity in protein responses and interactions following normal learning.
Nerve deafness associated with congenital syphilis; report of a case treated with prednisone and penicillin.

The nerve deafness of late congenital syphilis is usually an isolated neurological finding without concomitant evidence of neurosyphilis and without abnormalities in the cerebrospinal fluid. Keidel and Kemp 1 found 22 such cases among 230 patients with congenital syphilis. In contrast to most of the manifestations of syphilis, which respond to treponemicidal therapy and which can be attributed to the direct destructive effects of Treponema pallidum, the nerve deafness of late congenital syphilis does not respond to such therapy. 2 The scantiness of the postmortem material available permits no certain conclusions about the pathology or even the anatomic site of the lesion. Interstitial keratitis and Clutton's joints (intermittent hydrarthrosis of the knees), both manifestations of late congenital syphilis, behave like hypersensitivity phenomena in that they are resistant to therapy with penicillin but responsive to that with corticosteroids. In speculating about the nature of late isolated nerve deafness in congenital syphilis,
Pragmatic (trial) informatics: a perspective from the NIH Health Care Systems Research Collaboratory

Pragmatic clinical trials (PCTs) are research investigations embedded in health care settings designed to increase the efficiency of research and its relevance to clinical practice. The Health Care Systems Research Collaboratory, initiated by the National Institutes of Health Common Fund in 2010, is a pioneering cooperative aimed at identifying and overcoming operational challenges to pragmatic research. Drawing from our experience, we present 4 broad categories of informatics-related challenges: (1) using clinical data for research, (2) integrating data from heterogeneous systems, (3) using electronic health records to support intervention delivery or health system change, and (4) assessing and improving data capture to define study populations and outcomes. These challenges impact the validity, reliability, and integrity of PCTs. Achieving the full potential of PCTs and a learning health system will require meaningful partnerships between health system leadership and operations, and federally driven standards and policies to ensure that future electronic health record systems have the flexibility to support research.
From outsiders to Insiders? Partner choice and marriage among internal migrants in Antwerp, Rotterdam & Stockholm, 1850-1930

"Von Aussenseitem zu Etablierten? Partnerwahl und Heirat unter inleindischen Migranten in Antwerpen, Rotterdam und Stockholm, 1850-1930". Processes of social inclusion and exclusion among internal migrants in Antwerp, Rotterdam and Stockholm in the period 1850-1930 are studied with the help of data on partner choice and marriage of migrants who moved to these cities as singles. In practice, four outcomes related to meeting and mating are linked in our conceptual model to four acculturation trajectories, which form together a sliding scale in terms of social in- and exclusion. The models were tested by means of logistic regression. The results show that in all three cities social exclusion was a widespread phenomenon, and that only a small minority of the migrants became fully incorporated into urban mainstream society. Social exclusion was highly related to cultural differences between migrants and natives. Economic capital did not reduce the migrants' risk of facing marginalization, but it did facilitate the crossing of group boundaries for a specific group of migrants who were able to escape marginalization. The fact that social inclusion took place on a larger scale in Antwerp and Rotterdam compared to Stockholm suggests that large port cities facilitated the incorporation of migrants more than industrial cities.
Molecular controls of the oxygenation and redox reactions of hemoglobin.

SIGNIFICANCE The broad classes of O(2)-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O(2)-binding functions. RECENT ADVANCES The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. CRITICAL ISSUES An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. FUTURE DIRECTIONS This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes.
Pharmacodynamic Activity of Telithromycin at Simulated Clinically Achievable Free-Drug Concentrations in Serum and Epithelial Lining Fluid against Efflux (mefE)-Producing Macrolide- Resistant Streptococcus pneumoniae for Which Telithromycin MICs Vary

ABSTRACT The present study, using an in vitro model, assessed telithromycin pharmacodynamic activity at simulated clinically achievable free-drug concentrations in serum (S) and epithelial lining fluid (ELF) against efflux (mefE)-producing macrolide-resistant Streptococcus pneumoniae. Two macrolide-susceptible (PCR negative for both mefE and ermB) and 11 efflux-producing macrolide-resistant [PCR-positive for mefE and negative for ermB) S. pneumoniae strains with various telithromycin MICs (0.015 to 1 μg/ml) were tested. The steady-state pharmacokinetics of telithromycin were modeled, simulating a dosage of 800 mg orally once daily administered at time 0 and at 24 h (free-drug maximum concentration [Cmax] in serum, 0.7 μg/ml; half-life [t1/2], 10 h; free-drug Cmax in ELF, 6.0 μg/ml; t1/2, 10 h). Starting inocula were 106 CFU/ml in Mueller-Hinton Broth with 2% lysed horse blood. Sampling at 0, 2, 4, 6, 12, 24, and 48 h assessed the extent of bacterial killing (decrease in log10 CFU/ml versus initial inoculum). Free-telithromycin concentrations in serum achieved in the model were Cmax 0.9 ± 0.08 μg/ml, area under the curve to MIC (AUC0-24 h) 6.4 ± 1.5 μg · h/ml, and t1/2 of 10.6 ± 0.6 h. Telithromycin-free ELF concentrations achieved in the model were Cmax 6.6 ± 0.8 μg/ml, AUC0-24 h 45.5 ± 5.5 μg · h/ml, and t1/2 of 10.5 ± 1.7 h. Free-telithromycin S and ELF concentrations rapidly eradicated efflux-producing macrolide-resistant S. pneumoniae with telithromycin MICs up to and including 0.25 μg/ml and 1 μg/ml, respectively. Free-telithromycin S and ELF concentrations simulating Cmax/MIC ≥ 3.5 and AUC0-24 h/MIC ≥ 25 completely eradicated (≥4 log10 killing) macrolide-resistant S. pneumoniae at 24 and 48 h. Free-telithromycin concentrations in serum simulating Cmax/MIC ≥ 1.8 and AUC0-24 h/MIC ≥ 12.5 were bacteriostatic (0.1 to 0.2 log10 killing) against macrolide-resistant S. pneumoniae at 24 and 48 h. In conclusion, free-telithromycin concentrations in serum and ELF simulating Cmax/MIC ≥ 3.5 and AUC0-24 h/MIC ≥ 25 completely eradicated (≥4 log10 killing) macrolide-resistant S. pneumoniae at 24 and 48 h.
The Southern Oscillation in the Early 1990s

Two aspects of the onset of a warm event in the Southern Oscillation are 1) the subtropical South Pacific High is weakened in early southern winter which weakens subtropical sea level pressure (SLP) gradients, and thus reduces the trade winds and upwelling along the equator, and 2) in the months that follow, and particularly during the mature phase of the warm event during southern summer, the negative SST anomalies in the equatorial cold‐water tongue are displaced by positive anomalies and the water along the tropical Peruvian coast usually warms. To highlight the role of Southern Hemisphere subtropical processes in warm events, we focus on the first half of the 1990s. That period has been viewed as a five year warm event, but actually two warm events developed during this period according to the criteria in 1) and 2): in 1991 and 1994. This study emphasizes the importance of interactions between the subtropical and equatorial Pacific in warm events.
Cassette mutagenesis of the reverse transcriptase of human immunodeficiency virus type 1

We constructed a series of BspMI cassettes that simplify the introduction of specific point mutations in the polymerase domain of human immunodeficiency virus type 1 reverse transcriptase. A series of point mutants were constructed by using these cassette vectors. The RNA-dependent DNA polymerase and RNase H activities of 20 point mutations in the conserved portion of the polymerase domain were assayed. All the mutations analyzed are conservative substitutions of evolutionarily conserved amino acids. The mutations were divided into four classes. The first class has little effect on either polymerase or RNase H activity. The second class affects RNase H but not polymerase activity, while the third class has a normal RNase H activity with diminished polymerase activity. The fourth class affects both activities.
Flu Vaccines and Patient Decision Making: What We Need to Know

Purpose To describe and compare patient‐perceived barriers and motivators and decision‐making conflict between groups of hospitalized patients, those who received vaccines and those who did not. Data Sources Data collection included extracting data from databases and mailing two surveys to 436 discharged patients. One hundred eight patients participated in the study. Conclusions Top motivators for obtaining a flu vaccine included previous vaccination (93%) and provider recommendation (62%). Top barriers included fear of side effects the vaccine (35%) and fear of contracting the flu (30%). Motivators, barriers, and patient decisional conflict differed depending upon the patient's vaccination status. Implications for Practice Given the potential negative consequences of contracting the flu, prevention is the best strategy. Prevention contingent upon motivating patients to obtain an annual flu vaccine. Recommending flu vaccinations, offering vaccinations in convenient locations free of charge, discussing perceived barriers with patients may increase vaccinations among high‐risk patients. Helping to clarify the advantages and disadvantages from the patient's perspective may decrease decisional conflict and increase vaccination rates.
High Rates of AIDS-Related Mortality Among Older Adults in Rural Kenya

Background:Health challenges faced by older people in developing countries are often neglected amidst a wide range of competing priorities. This is evident in the HIV field where the upper age limit for reporting HIV prevalence remains 49 years. However, the long latency period for HIV infection, and the fact that older people continue to be sexually active, suggests that HIV and AIDS are likely to affect older people. To better understand this, we studied mortality due to AIDS in people aged 50 and older in an area of rural Kenya with high rates of HIV infection. Methods:A community health worker-administered verbal autopsy system was introduced in Nyanza Province, encompassing 63,500 people. Algorithms were used to determine cause of death. Results:A total of 1228 deaths were recorded during the study period; 368 deaths occurred in people aged 50 years and older. AIDS was the single most common cause of death, causing 27% of all deaths. AIDS continued to be the main cause of death up to age 70 years, causing 34% of deaths in people aged 50-59 years and 23% of deaths in people aged 60-69 years. Conclusions:AIDS remains the principle cause of death among older people in Nyanza Province in western Kenya up until the age of 70 years. Greater efforts are needed to integrate older people into the HIV response and to better understand the specific vulnerabilities and challenges faced by this group.
Turgor pressure moves polysaccharides into growing cell walls of Chara corallina.

BACKGROUND AND AIMS Plant growth involves pressure-driven cell enlargement generally accompanied by deposition of new cell wall. New polysaccharides are secreted by the plasma membrane but their subsequent entry into the wall is obscure. Therefore, polysaccharides and gold colloids of various sizes were presented to the inner wall face as though they were secreted by the plasma membrane. METHODS Primary cell walls were isolated from growing internodes of Chara corallina and one end was attached to a glass capillary. Solutions of dextran or suspensions of gold colloids were pushed into the lumen by oil in the capillary. The oil did not enter the wall, and the solution or suspension was pressed against the inner wall face, pressurized at various 'artificial' P (turgor pressure), and polymer or colloid movement through the wall was monitored. KEY RESULTS Interstices in the wall matrix had a diameter of about 4.6 nm measured at high P with gold colloids. Small solute (0.8 nm) readily moved through these interstices unaffected by P. Dextrans of 3.5 nm diameter moved faster at higher P while dextran of 9 nm scarcely entered unless high P was present. Dextran of 11 nm did not enter unless P was above a threshold, and dextran of 27 nm did not enter at P as high as 0.5 MPa. The walls filtered the dextrans, which became concentrated against the inner wall face, and most polymer movement occurred after P stabilized and bulk flow ended. CONCLUSIONS P created a steep gradient in concentration and mechanical force at the inner wall face that moved large polymers into small wall openings apparently by starting a polymer end or deforming the polymer mechanically at the inner wall face. This movement occurred at P generally accepted to extend the walls for growth.