Miracle-dz/UniFAR-FTUs huggingface dataset:
Sedatives, Analgesics, and Paralytics in the Icu

Objective To solicit practitioner-perceived opinions regarding current sedative/analgesic/paralytic practice including drug selection, admixture methods, and methods of assessing patient response to therapy via a survey tool; and to assess sedative/pain/paralytic drug use patterns including dosage, route, selection, and combination therapy by collecting actual drug administration data from multiple centers. Methods Respondents completed a survey and collected drug administration data for 5 consecutive days in the intensive care unit (ICU) in which they practiced. Participants One hundred thirty-eight members of the Society of Critical Care Medicine Clinical Pharmacology and Pharmacy section and the Critical Care Practice Research Network of the American College of Clinical Pharmacy agreed to participate in the study. Results Fifty-one percent of the participants completed surveys, and 45% returned drug administration data collection forms. Patients received sedative/pain/paralytic therapy 62% of the 5 days studied. The most frequently received drugs were opiates, followed by benzodiazepines. Intermittent intravenous injection, oral/enteral, and continuous infusion methods were used in most patients. Combination therapy was used 25% of the time, with benzodiazepine/opiate combinations used most often (46%). Administration protocols were rarely used. Paralytic agents were occasionally administered without sedative/pain therapy. Conclusions Patients received these agents during the majority of their ICU stay. Multicenter drug use data suggested a preference for opiate and benzodiazepine therapy. Many centers used continuous infusion therapy despite minimal pharmacokinetic/pharmacodynamic information on ICU patients. Further studies are needed to standardize end points, as well as obtain both pharmacokinetic/pharmacodynamic and stability data in ICU patients.
The outcome of bacterial arthritis: a prospective community-based study.

OBJECTIVE To assess the outcome and adverse prognostic factors of bacterial arthritis (BA). METHODS In a prospective community survey of BA, data were collected at the time of diagnosis and at a mean of 2 years later. A poor patient outcome was defined as death due to BA or severe overall functional deterioration. A poor joint outcome was defined as amputation, arthrodesis, prosthetic surgery, or severe functional deterioration. Possible prognostic factors were analyzed by univariate analysis. RESULTS BA was diagnosed in 154 patients, 121 adults and 33 children. One-half of the adults had a preexisting joint disease and 29% of the infected joints contained synthetic material. The patient outcome was poor in 21% of all patients, and the joint outcome was poor in 33% of the surviving patients. Adverse prognostic factors were an older age, preexisting joint disease, and an infected joint containing synthetic material. These factors were interrelated. There was no association between a poor outcome and young age, comorbidity, immunosuppressive medication, functional class, multiple infected joints, type of microorganism, or treatment delay. CONCLUSION BA had a poor outcome in almost one-half of the patients. Patients who were older, had a preexisting joint disease, and/or had an infected joint containing synthetic material had the poorest prognosis.
A case of 3q29 microdeletion with novel features and a review of cytogenetically visible terminal 3q deletions

A further case of 3q29 deletion, in a 13-year-old boy, is described and compared with previous reports. Our case shares a number of dysmorphic and neurodevelopmental features with previously reported individuals with 3q29 microdeletion and is the second reported case with deceleration in head growth – which may be a useful diagnostic clue. Novel features, which may expand the phenotype, include nasal voice, six lumbar vertebrae, lower limb contractures and cerebral sigmoid venous thrombosis. Additionally, cases with cytogenetically visible terminal 3q deletions are reviewed.
oxidation by laser-induced pacemakers Control of spatiotemporal chaos in catalytic CO

References html#ref-list-1 http://rsta.royalsocietypublishing. org/content/366/1864/419.full. This article cites 20 articles, 3 of which can be accessed free Rapid response 1864/419 http://rsta.royalsocietypublishing. org/letters/submit/roypta;366/ Respond to this article Email alerting service here in the box at the top right-hand corner of the article or click Receive free email alerts when new articles cite this article sign up
Higher Binding of the Dopamine D3 Receptor-Preferring Ligand [11C]-(+)-Propyl-Hexahydro-Naphtho-Oxazin in Methamphetamine Polydrug Users: A Positron Emission Tomography Study

Positron emission tomography (PET) findings suggesting lower D2-type dopamine receptors and dopamine concentration in brains of stimulant users have prompted speculation that increasing dopamine signaling might help in drug treatment. However, this strategy needs to consider the possibility, based on animal and postmortem human data, that dopaminergic activity at the related D3 receptor might, in contrast, be elevated and thereby contribute to drug-taking behavior. We tested the hypothesis that D3 receptor binding is above normal in methamphetamine (MA) polydrug users, using PET and the D3-preferring ligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin ([11C]-(+)-PHNO). Sixteen control subjects and 16 polydrug users reporting MA as their primary drug of abuse underwent PET scanning after [11C]-(+)-PHNO. Compared with control subjects, drug users had higher [11C]-(+)-PHNO binding in the D3-rich midbrain substantia nigra (SN; +46%; p < 0.02) and in the globus pallidus (+9%; p = 0.06) and ventral pallidum (+11%; p = 0.1), whereas binding was slightly lower in the D2-rich dorsal striatum (approximately −4%, NS; −12% in heavy users, p = 0.01) and related to drug-use severity. The [11C]-(+)-PHNO binding ratio in D3-rich SN versus D2-rich dorsal striatum was 55% higher in MA users (p = 0.004), with heavy but not moderate users having ratios significantly different from controls. [11C]-(+)-PHNO binding in SN was related to self-reported “drug wanting. ” We conclude that the dopamine D3 receptor, unlike the D2 receptor, might be upregulated in brains of MA polydrug users, although lower dopamine levels in MA users could have contributed to the finding. Pharmacological studies are needed to establish whether normalization of D3 receptor function could reduce vulnerability to relapse in stimulant abuse.
AP-1 homolog BZLF1 of Epstein–Barr virus has two essential functions dependent on the epigenetic state of the viral genome

EBV, a member of the herpes virus family, is a paradigm for human tumor viruses and a model of viral latency amenable for study in vitro. It induces resting human B lymphocytes to proliferate indefinitely in vitro and initially establishes a strictly latent infection in these cells. BZLF1, related to the cellular activating protein 1 (AP-1) family of transcription factors, is the viral master gene essential and sufficient to mediate the switch to induce the EBV lytic phase in latently infected B cells. Enigmatically, after infection BZLF1 is expressed very early in the majority of primary B cells, but its early expression fails to induce the EBV lytic phase. We show that the early expression of BZLF1 has a critical role in driving the proliferation of quiescent naïve and memory B cells but not of activated germinal center B cells. BZLF1’s initial failure to induce the EBV lytic phase relies on the viral DNA at first being unmethylated. We have found that the eventual and inevitable methylation of viral DNA is a prerequisite for productive infection in stably, latently infected B cells which then yield progeny virus lacking cytosine-phosphatidyl-guanosine (CpG) methylation. This progeny virus then can repeat EBV’s epigenetically regulated, biphasic life cycle. Our data indicate that the viral BZLF1 protein is crucial both to establish latency and to escape from it. Our data also indicate that EBV has evolved to appropriate its host’s mode of methylating DNA for its own epigenetic regulation.
Microneutralization test for respiratory syncytial virus based on an enzyme immunoassay

Virus infectivity and antibody neutralization titers for respiratory syncytial virus were determined in cell cultures in microtiter plates. After an appropriate incubation period, the cells were fixed, and an enzyme-linked immunosorbent assay was performed directly in the microtiter plates for detection of virus. Results could be read and recorded automatically, which is especially helpful when running large numbers of tests.
Interaction between Two Putative Glycosyltransferases Is Required for Glycosylation of a Serine-Rich Streptococcal Adhesin

ABSTRACT Fap1, a serine-rich glycoprotein, is essential for fimbrial biogenesis and biofilm formation of Streptococcus parasanguinis (formerly S. parasanguis). Fap1-like proteins are conserved in many streptococci and staphylococci and have been implicated in bacterial virulence. Fap1 contains two serine-rich repeat regions that are modified by O-linked glycosylation. A seven-gene cluster has been identified, and this cluster is implicated in Fap1 biogenesis. In this study, we investigated the initial step of Fap1 glycosylation by using a recombinant Fap1 as a model. This recombinant molecule has the same monosaccharide composition profile as the native Fap1 protein. Glycosyl linkage analyses indicated that N-acetylglucosamine (GlcNAc) is among the first group of sugar residues transferred to the Fap1 peptide. Two putative glycosyltransferases, Gtf1 and Gtf2, were essential for the glycosylation of Fap1 with GlcNAc-containing oligosaccharide(s) in both S. parasanguinis as well as in the Fap1 glycosylation system in Escherichia coli. Yeast two-hybrid analysis as well as in vitro and in vivo glutathione S-transferase pull-down assays demonstrated the two putative glycosyltransferases interacted with each other. The interaction domain was mapped to an N-terminal region of Gtf1 that was required for the Fap1 glycosylation. The data in this study suggested that the formation of the Gtf1 and Gtf2 complex was required for the initiation of the Fap1 glycosylation and that the N-terminal region of Gtf1 was necessary.
Quantitative Assessment of Gastric Antrum Atrophy Shows Restitution to Normal Histology after Helicobacter pylori Eradication

Background/Aims: Grading gastric mucosal atrophy in antrum biopsy specimens remains a controversial subject because of limitations in interobserver agreement. We previously described a reliable, quantitative method for grading atrophy of the corpus mucosa with excellent reproducibility and good correlation with the Sydney scores. The aims of the present study were to evaluate the applicability of this method for the grading of antral atrophy and to study the effect of Helicobacter pylori eradication on the antral mucosa. Methods: Antrum biopsy specimens were collected from 71 gastroesophageal reflux disease patients at baseline and after 3 and 12 months. After the first endoscopy, all subjects were treated with omeprazole 40 mg daily for 12 months. After randomization, 27 of the 48 H. pylori-positive patients additionally received eradication therapy. In 182 hematoxylin-eosin-stained specimens, which were of sufficient quality, the proportions (volume percentages) of glands (VPGL), stroma (VPS), infiltrate (VPI), and intestinal metaplasia in the glandular zone of the antrum mucosa were measured using a point-counting method. In these specimens, mucosal atrophy was assessed by two experienced gastrointestinal tract pathologists (E.B. and J.L.) according to the updated Sydney classification as either nonatrophic mucosa (n = 47) or as mild (n = 29), moderate (n = 50), or marked (n = 56) atrophy. In addition, a group of 23 cases with difficult-to-classify grades of atrophy were included. Results: The mean VPGL decreased with increasing Sydney grades of atrophy (p < 0.001), while the mean VPS and VPI increased (both p < 0.001). After H. pylori eradication, even the cases with the lowest VPGL regressed to normal levels. Conclusions: Overall, a low VPGL correlates with increasing grades of antrum mucosal atrophy. The present data indicate that gastric mucosal atrophy is reversible, since almost all cases showed regression of VPGL after H. pylori eradication. The cases with difficult-to-classify grades of atrophy showed significantly lower VPGLs and higher VPIs than the reference cases.
LOX-1 Deletion Improves Neutrophil Responses, Enhances Bacterial Clearance, and Reduces Lung Injury in a Murine Polymicrobial Sepsis Model

ABSTRACT Inflammatory tissue injury and immunosuppression are the major causes of death in sepsis. Novel therapeutic targets that can prevent excessive inflammation and improve immune responses during sepsis could be critical for treatment of this devastating disease. LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1), a membrane protein expressed in endothelial cells, has been known to mediate vascular inflammation. In the present study, we demonstrated that LOX-1 deletion markedly improved the survival rate in a murine model of polymicrobial sepsis. Wild-type (LOX-1+/+) and LOX-1 knockout (LOX-1−/−) mice were subjected to cecal ligation and puncture (CLP) to induce sepsis. LOX-1 deletion significantly reduced systemic inflammation and inflammatory lung injury during sepsis, together with decreased production of proinflammatory cytokines and reduced lung edema formation. Furthermore, LOX-1 deletion improved host immune responses after the induction of sepsis, as indicated by enhanced bacterial clearance. Interestingly, we were able to demonstrate that LOX-1 is expressed in neutrophils. LOX-1 deletion prevented neutrophil overreaction and increased neutrophil recruitment to infection sites after sepsis induction, contributing at least partly to increased immune responses in LOX-1 knockout mice. Our study results indicate that LOX-1 is an important mediator of inflammation and neutrophil dysfunction in sepsis.
Megamarsupial extinction: the carrying capacity argument

An ancient and contentious debate in prehistory (Owen 1846; Lyell 1863) asks if the megafauna of newly colonized worlds was exterminated by human hunting, or whether other factors, such as changing climate, were decisive. Debate on this issue remains lively in Australia, because its harsh environments surely posed problems for very large mammals. A starting-point for this fresh look at megafaunal extinction was Flannery's (1994) adoption of the ‘blitzkrieg’ hypothesis, in which humanly caused kill-off was so rapid it left no decisive archaeological traces.
Dysphonia associated with the use of inhaled corticosteroids

Purpose of review This article discusses the relationship between inhaled corticosteroids and dysphonia, with discussion of the therapeutic use of inhaled steroids in laryngeal disease and a review of negative laryngeal effects of this class of medication in patients with reactive airway disease. Recent findings Although prescribed for their anti-inflammatory effects (predominantly for pulmonary disease and less often for laryngeal conditions), corticosteroid inhalers can cause laryngeal inflammation. This may relate to chemical irritation from the inhaler itself as well as fungal inflammation related to opportunistic candidiasis that may accompany inhaler use. Patients who suffer from dysphonia because of inhaler use may improve if switched to another inhaler. Studies suggest that ciclesonide metered-dose inhaler may have less oropharyngeal deposition and therefore be associated with reduced oropharyngeal candidiasis and dysphonia compared with other inhaled corticosteroids. Summary Corticosteroid inhalers are a common cause of dysphonia and their use should be investigated in any patient with laryngeal complaints.
Détection et caractérisation moléculaires rapides du virus de la peste porcine africaine et utilisation des reconstructions phylogénétiques pour reconstituer son histoire évolutive

La Peste porcine africaine (PPA) est une maladie contagieuse specifique du porc domestique due au seul arbovirus a ADN identifie a ce jour. Decrite pour la premiere fois en 1921 au Kenya, la maladie a ensuite diffuse dans de nombreuses regions du monde. Malgre l'isolement de nombreuses souches virales au cours du temps, peu d'etudes phylogenetiques ont ete menees jusqu'ici pour comprendre les relations unissant ces isolats entre eux. Or, la caracterisation est essentielle a la tracabilite des souches et donc a la comprehension de l'epidemiologie de la maladie. De plus, les conditions climatiques et environnementales des principaux pays atteints rendent difficiles l'acces, le transport et la conservation de nouvelles souches. Dans cette these, un protocole de prelevement et de conservation du sang a ete developpe, pour la detection et la caracterisation rapides des souches. Une etude phylogenetique approfondie a ete realisee en utilisant des donnees de sequences publiques et inedites de virus isoles depuis 1950. Les analyses ont porte sur les genes B646L, CP204L et E183L. Les analyses phylogenetiques ont utilise les methodes de maximum de vraisemblance et d'inference bayesienne, qui ont permis de proposer une nouvelle nomenclature virale en 35 clusters differents. De plus, une datation des origines du virus a ete menee, apres avoir elimine les biais d'analyse dus a une pression de selection positive et/ou aux recombinaisons. L'horloge moleculaire a permis de determiner que l'ancetre commun le plus proche des souches contemporaines (TMRCA) se situait au debut du 18eme siecle. (Presentation de l'editeur)
Kinetic analysis of glycyrrhetic acid, an active metabolite of glycyrrhizin, in rats: role of enterohepatic circulation.

The role of enterohepatic circulation of glycyrrhetic acid (GA) in rats was determined by kinetic analysis of GA. The concentrations of GA in the plasma of the control rat (without bile duct cannulation) during the first 5 h after intravenous (iv) administration of GA (2, 5, 10, and 20 mg/kg) were similar to those in the bile duct-cannulated rat at each dose. No significant difference was observed in the values of the terminal half-life, the total body clearance, the distribution volume at steady state, the area under the curve of concentration in plasma versus time, and the mean residence time in each dose between both groups. When GA (2, 5, 10, and 20 mg/kg) was administered i.v. to the bile duct-cannulated rat, excretion of unchanged GA in bile was < 1% of each dose, that of the acid-hydrolyzed products was 14-16%, and that of GA-3-O-glucuronide was only 1-2%. In the control rat, a secondary peak of GA concentration was observed 12 h after i.v. administration of GA (20 mg/kg). The enterohepatic circulation of GA was confirmed by the linked-rat method in which bile of the donor rat after i.v. administration of GA (20 mg/kg) was allowed to flow directly into the duodenum of the recipient rat. GA was found in the plasma of the recipient rat after 6 h, and its concentration reached the maximum (approximately 0.5 microgram/mL) 8-12 h after dosing the donor rat. (ABSTRACT TRUNCATED AT 250 WORDS)
RELATIONSHIPS BETWEEN THE CIRCADIAN RHYTHMS OF TSH, PROLACTIN AND CORTISOL IN SURGICALLY TREATED MICROPROLACTINOMA PATIENTS

Pharmacological doses of glucocorticoids inhibit TSH release both in vivo and in vitro and since the circadian rhythms of TSH and cortisol show a reciprocal relationship, the hypothesis has been advanced that changes in cortisol levels may be a primary determinant of circadian TSH changes. We have tested this hypothesis by studying the relationship between circadian cortisol and TSH rhythms in subjects before and during blockade with metyrapone. Seven patients were studied during their routine post‐operative assessment following selective transethmoidal adenomectomy for microprolactinomas. PRL levels were restored to normal (<420 mU/l) in all patients by surgery (pre‐op: 930–2752 mU/1, post‐op: 33–376 mU/1) and the patients also had normal pituitary function in other respects. Blood was sampled hourly for 24 h before and on the third day of treatment with metyrapone (250 mg, 2 hourly). In order to compare circadian rhythms, hormonal data were subjected to cosinor analysis which involved fitting of the data with a cosine function using the method of least squares. The 6% cross reactivity of the Cortisol antibody with 11‐deoxycortisol was taken into account during the calculation of results. All subjects showed a normal Cortisol rhythm which was strikingly blunted during metyrapone treatment. Group mean (± SD) TSH mesors, amplitudes and acrophases for control and metyrapone treated subjects were 1.5 ± 0.26, 1.29 ± 0.48; 0.46 ± 0.26, 0.23 ± 0.13 and −49°± 9.8°; −62°± 2.7° respectively. Based on paired t‐testing of these data there was a small but significant reduction in the amplitude (P<0.05) and acrophase (P<0.05) of the TSH rhythm during metyrapone administration but no alteration in the circadian pattern of change. The normal circadian change in PRL levels which we observed in these patients was not altered by metyrapone treatment. It appears therefore that variation in endogenous cortisol is not the sole factor involved in the determination of the circadian TSH rhythm and that it does not influence circadian PRL changes in this group of subjects.
The influence of mental load on muscle tension

We examined the differences in muscle tension and in physiological measures depending on the type of mental task. Fifteen participants performed tests for sustained attention, vigilance and maintaining posture only. We analysed electromyogram (EMG) measures of extensor digitorum (ED), flexor carpi ulnaris (FU), deltoideus (DE) and trapezius (TR), and heart rate (HR) and respiratory frequency (RF). Measures indicated higher values for mental tasks than for maintained posture only with significant differences in all measures. The following relationships were also significant: between DE and physiological measures (HR and RF), between ED and the amplitude of EMG of the other three muscles, between FU and TR and between HR and RF. The results of this study showed that the relationship between mental demands and muscle tension was mostly reflected by tension in the arm and shoulder girdle muscles and, to a lesser degree, in forearm muscles. Practitioner Summary: We focused on physiological and muscle tension measures differentiating work according to the level of mental demands. Differences in sustained attention, vigilance and maintaining posture only proved that mental demands were mostly reflected by tension in arm and shoulder girdle muscles and, to a lesser degree, in forearm muscles.
Alteration of lipid composition of rat thymus during thymic atrophy by whole-body X-irradiation

Purpose:Thymic atrophy induced by irradiation is well known, but in vivo lipid metabolism during the atrophy has not been studied in detail. We determined the lipid composition of rat thymus during the progress of thymic atrophy induced by whole-body X-irradiation. Materials and methods:The lipid analysis of total lipid of rat thymus after 5 Gy whole-body X-irradiation was performed by high performance liquid chromatography and gas chromatography equipped with mass spectrometry. Results:Major changes observed were a 16.2-fold elevation of cholesterol ester (CE) during a 48-h post-irradiation period and a 6.1-fold increase of alkyldiacylglycerol (ADG) at 24 h. Other significant changes detected were an increase in lysophosphatidylcholine and a transient increase in ceramide and phosphatidic acid. Acyl chain analysis revealed a substantial elevation of arachidonate composition of CE and an unusually high content of polyunsaturated fatty acids (71.5%, mol/mol) in ADG. Conclusion:Lipid analysis shows that the thymic atrophy by X-irradiation was accompanied by a significant change in thymic lipids. This in vivo result opens up new vistas of the role of lipids in apoptosis and phagocytosis during thymic atrophy.