Miracle-dz/UniFAR-FTUs huggingface dataset:
An official American Thoracic Society policy statement: managing conscientious objections in intensive care medicine.

RATIONALE Intensive care unit (ICU) clinicians sometimes have a conscientious objection (CO) to providing or disclosing information about a legal, professionally accepted, and otherwise available medical service. There is little guidance about how to manage COs in ICUs. OBJECTIVES To provide clinicians, hospital administrators, and policymakers with recommendations for managing COs in the critical care setting. METHODS This policy statement was developed by a multidisciplinary expert committee using an iterative process with a diverse working group representing adult medicine, pediatrics, nursing, patient advocacy, bioethics, philosophy, and law. MAIN RESULTS The policy recommendations are based on the dual goals of protecting patients' access to medical services and protecting the moral integrity of clinicians. Conceptually, accommodating COs should be considered a "shield" to protect individual clinicians' moral integrity rather than as a "sword" to impose clinicians' judgments on patients. The committee recommends that: (1) COs in ICUs be managed through institutional mechanisms, (2) institutions accommodate COs, provided doing so will not impede a patient's or surrogate's timely access to medical services or information or create excessive hardships for other clinicians or the institution, (3) a clinician's CO to providing potentially inappropriate or futile medical services should not be considered sufficient justification to forgo the treatment against the objections of the patient or surrogate, and (4) institutions promote open moral dialogue and foster a culture that respects diverse values in the critical care setting. CONCLUSIONS This American Thoracic Society statement provides guidance for clinicians, hospital administrators, and policymakers to address clinicians' COs in the critical care setting.
The endothelial glycocalyx: a review of the vascular barrier

The endothelial glycocalyx is an important part of the vascular barrier. The glycocalyx is intimately linked to the homoeostatic functions of the endothelium. Damage to the glycocalyx precedes vascular pathology. In the first part of this paper, we have reviewed the structure, physiology and pathology of the endothelial glycocalyx, based on a literature search of the past five years. In the second part, we have systematically reviewed interventions to protect or repair the glycocalyx. Glycocalyx damage can be caused by hypervolaemia and hyperglycaemia and can be prevented by maintaining a physiological concentration of plasma protein, particularly albumin. Other interventions have been investigated in animal models: these require clinical research before their introduction into medical practice.
Improved immunohistochemical detection of postsynaptically located PSD‐95/SAP90 protein family by protease section pretreatment: A study in the adult mouse brain

Postsynaptic density (PSD)–95, SAP102, and Chapsyn‐110 are members of the PSD‐95/SAP90 protein family, which interact with the C‐terminus of N‐methyl‐D‐aspartate (NMDA) receptor and shaker‐type potassium channel subunits. Here we report that appropriate section pretreatment with pepsin has led to qualitative and quantitative changes in light microscopic immunohistochemical detection of the protein family. First, pepsin pretreatment lowered the concentration of affinity‐purified primary antibodies, while it greatly increased the intensity of immunoreactions. Second, the resulting overall distributions of PSD‐95, SAP102, and Chapsyn‐110 in the adult mouse brain were consistent with their mRNA distributions. Third, instead of the reported patterns of somatodendritic labeling, tiny punctate staining in the neuropil became overwhelming. Fourth, many PSD‐95‐immunopositive puncta were apposed closely to synaptophysin‐positive nerve terminals and overlapped with NMDA receptor subunits. By postembedding immunogold, the PSD‐95 antibody was shown to label exclusively the postsynaptic density at asymmetrical synapses. Based on these results, we conclude that antibody access and binding to the postsynaptically located PSD‐95/SAP90 protein family are hindered when conventional immunohistochemistry is adopted, and that pepsin pretreatment effectively unmasks the postsynaptic epitopes. On the other hand, PSD‐95 in axon terminals of cerebellar basket cells, where high levels of potassium channels are present, was detectable irrespective of pepsin pretreatment, suggesting that PSD‐95 antibody is readily accessible to the presynaptic epitopes. Consequently, the present immunohistochemical results have provided light microscopic evidence supporting the prevailing notion that the PSD‐95/SAP90 protein family interacts with NMDA receptor subunits and potassium channel subunits. J. Comp. Neurol. 426:572–586, 2000. © 2000 Wiley‐Liss, Inc.
Evolutionary Consequences of Sperm Cell Aging

Animal breeding research, reproductive biology, and cellular biogerontology show that fertilization rates and zygote viability critically depend on sperm age. Sexual selection research focuses on differences between male genotypes in sperm performance, such as motility, competitive ability, or compatibility with eggs, but without considering sperm age. A combined view (that the thermodynamically inevitable decline in sperm performance selects for traits in diploid individuals to prevent fertilization with aged sperm) has received very little attention. In this paper, I correct this bias and show that many male and female traits affect sperm aging or the sperm age distribution at any reproductive event. Such traits coincide well with condition‐dependent traits considered sexually selected: multiple mating by both sexes, high sperm production rates, the delivery of dense ejaculates containing many sperm (including nonfertilizing types), the packaging of sperm into spermatophores, male and female sperm ejection, sexual coercion, as well as the production of showy antioxidants and various cellular and nuclear repair mechanisms. I conclude that altering the sperm age distribution at any step during reproduction can be an origin of sexually selected traits, and may explain presently observed paternity variation without assuming genetic incompatibility of gametes.
Selective Flocculation and Precipitation for the Improvement of Virus‐Like Particle Recovery from Yeast Homogenate

The purification of an intracellular product from a complex mixture of contaminants after cell disruption is a common problem in processes downstream of fermentation systems. This is particularly challenging for the recovery of particulate (80 nm in diameter) multimeric protein products, named virus‐like particles (VLPs), from cell debris and other intracellular components. Selective flocculation for debris removal followed by selective precipitation of the target protein can be used as a preclarification step to aid purification. In this paper, selective borax flocculation of cell debris in yeast homogenate, followed by selective poly(ethylene glycol) precipitation of VLPs are defined with a view to demonstrating their potential in aiding the initial clarification stages of the purification sequence. The translation from laboratory scale to pilot scale operation is addressed, demonstrating the challenge of scale‐up of solid‐liquid separation stages for biological particle processing.
Teaching Systems Development: A Compelling Case for Integrating the SDLC with the ITSM Lifecycle

This paper raises awareness of industry's move to blend ITSM lifecycle concepts with the systems development lifecycle to foster collaboration between the silos of systems development and IT operations. Academia has an important role in integrating ITSM into traditional systems development coursework. The case of systems development is used to illustrate the types of IT service management concepts and models that can be introduced into current systems development offerings to support the focus on IT services being called for by industry today.
Sex-related differences in clinical drug response: implications for women's health.

Increasing evidence suggests that women have different patterns of drug metabolism and responsiveness throughout their life cycle and that these differences may be clinically significant. It is argued that sex related pharmacologic variations deserve clinical and basic research attention. Recent evidence is presented that gonadal sex steroids affect drug response metabolism and toxicity or adverse side effects. Since drug interactions are routinely monitored including those for estrogens and oral contraceptives (OCs) this database was examined for evidence that might be pertinent to the endogenous gonadal sex steroids and hence to the question of possible sex related differences in drug response. A pharmacological model was developed as defined in terms of exogenous estrogens and OC pills of sex related differences in pharmacological responsibility. Based on a selective literature review that is summarized in a table it was found that estrogens and OCs affect the therapeutic response of a wide variety of commonly used drugs including antiepileptics and antianxiety agents antidiabetics antidepressants anti-Parkinsons agents and thyroid medication. Although the magnitude and prevalence of these pharmacological effects are unclear it appears that the clinical implications deserve further study. Evidence was found for sex related differences as well as menstrual and menopausal variations in a variety of neurochemical systems. 1 example concerns evidence of a premenstrual impairment in oral glucose tolerance that is paralleled by a decrease in insulin receptors hence the question of possible menstrual or menopausal related exacerbations in certain diabetics appears to warrant further investigation. It appears that not only daily but also monthly cycles in drug metabolism may occur and that these alterations may be reflected in menstrual cycle related alterations in blood and tissue levels of drugs. 1 index of drug metabolism capacity antipyrine is decreased with OCs suggesting possible sex related effects. The question arises as to what are mechanisms that give rise to sex related differences in drug response or toxicity. Although gonadal sex steroids affect drug metabolism other possibilities must also be explored ranging from genetic sex to developmental differences in brain differentiation and laterilization. The kind of careful work needed in order to elucidate sex related differences in pharmacologic response includes study of whether the sex related variation is age dependent abolished by the administration of estrogen to the male dependent on sexual differentiation of the brain dependent on sex differences in metabolic clearance rate or on lack of weight normalization or dose dependent on estrogen.
Brevetoxins: unique polyether dinoflagellate toxins

Brevetoxins are lipid‐soluble polyether marine toxins of unique structure and pharmacological function. Toxins are active in vivo in the nanomolar to picomolar concentration range and in vitro in isolated neuromuscular or giant axon preparations and in single‐cell or subcellular model systems. Their effect is excitatory, mediated by the enhancement of cellular Na+ influx. Brevetoxins bind at site 5 on the voltage‐sensitive sodium channel, a specificity shared with ciguatoxin. This site is allosterically linked to other natural toxin binding sites on the channel. —Baden, D. G. Brevetoxins: unique polyether dinoflagellate toxins. FASEB J. 3: 1807‐1817; 1989.
A novel membrane sodium current induced by injection of cyclic nucleotides into gastropod neurones.

Injection of cyclic AMP (cAMP) or cyclic GMP into identifiable neurones from several different gastropod species immediately depolarized the cell membranes in a dose‐dependent manner. Doses were monitored photometrically and evidence is presented for depolarizing effects following nucleotide injections of as little as 30‐35 mumol. The depolarizing effect was reversible and was demonstrated under voltage clamp to be primarily the result of a nucleotide‐induced, transient increase in a membrane Na current, INa (cAMP). The charge‐carrying species was identified by using ion‐substituted salines, reversal potential in low‐Na saline, and intracellular ion‐sensitive electrode measurements. The current was resistant to tetrodotoxin, ouabain and amiloride. Substituting Trisma, tetramethylammonium or bis‐tris propane for Na prevented the induced current, whereas Li substitution did not. Duration of the induced current was greatly prolonged in neurones bathed in the phosphodiesterase inhibitor isobutylmethylxanthine, or following injection of any of several cAMP analogues, indicating that the reversible nature of the current stems primarily from in situ hydrolysis of the injected dose and not current inactivation. Amplitude of the induced current either remained constant or decreased over the voltage range where it could be easily measured, i.e. ‐30 greater than Vm greater than ‐100 mV, reflecting a voltage as well as a chemical sensitivity of INa (cAMP).
Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer.

BACKGROUND Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous infusion repeatedly over 5 to 8 cycles. Intraperitoneal chemotherapy (IP) is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. This may increase the anticancer effect with fewer systemic adverse effects in comparison to intravenous therapy. OBJECTIVES To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression free survival, quality of life (QOL) and toxicity for women receiving primary treatment of epithelial ovarian cancer. SEARCH STRATEGY The reviewers searched the UK Cochrane trials register, Gynaecological Cancer Group Specialised Register, computer databases and handsearched and cascade searched the major gynaecological oncology journals. SELECTION CRITERIA The analysis was restricted to randomised controlled trials assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard intravenous chemotherapy was compared with chemotherapy that included a component of intraperitoneal administration. DATA COLLECTION AND ANALYSIS Two reviewers conducted data extraction independently. The reviewers retrieved data on overall and disease free survival as well as adverse events and QOL and then performed a meta-analysis of outcomes, using hazard ratios for time-to-event variables and relative risks for dichotomous outcomes. MAIN RESULTS Eight randomised trials studied 1819 women receiving primary treatment for ovarian cancer. Women were less likely to die if they received an intraperitoneal (IP) component to the chemotherapy (hazard ratio (HR) =0.79; 95% confidence interval (CI): 0.70 to 0.90)and the disease free interval (HR =0.79; 95%CI: 0.69 to 0.90) was also significantly prolonged. There may be greater serious toxicity with regard to gastrointestinal effects, pain and fever but less ototoxicity with the intraperitoneal than the intravenous route. AUTHORS' CONCLUSIONS This analysis establishes the benefit of IP chemotherapy. It increases overall survival and progression free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of this decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials.
Association between Excess Bodyweight and Intake of Red Meat and Vegetables among Urban and Rural Adult Chinese in Nanjing, China

The objective of this study was to examine the association of red meat and vegetable consumption with excess bodyweight. This is a cross sectional study, conducted between October 2000 and March 2001. Participants included 23,316 local residents aged 35 and above from 45 administrative villages randomly selected from urban and rural areas of Nanjing, China, with a population of 5.6 million. The response rate was 90.1%. Logistic regression model was used for the analysis. The prevalence of excess body weight, overweight and obesity was 34.1%, 28.2% and 6.0%, respectively. After adjustment for age, educational attainment, family average income, occupational and leisure-time physical activity, smoking, drinking, consumption of white meat, consumption of rice and cooking oil as well as fruits, participants in the moderate or higher level of red meat consumption were more likely to have excess body weight (OR: 1.13 (95% CI=1.02, 1.26) and 1.15 (1.02, 12.9) for males; 1.11 (0.98, 1.25) and 1.25 (1.10, 1.42) for females respectively), compared with those in the lower level of red meat consumption. There was no statistically significant association for consumption of vegetables. Consumption of more red meat was suggested to be a factor contributing to body weight gain in China. For residents who want to have healthy body weight, it is important to consume less red meat in the process of socioeconomic transition. Asia Pac J Public Health 2007; 19(3): 3-9.
The RpoS Sigma factor relieves H‐NS‐mediated transcriptional repression of csgA, the subunit gene of fibronectin‐binding curli in Escherichia coli

Curli encoded by the curlin subunit gene, csgA, are fibronectin‐ and laminin‐binding fibres expressed by many natural Escherichia coli and E. coli K‐12 strains in response to low temperature, low osmolarity and stationary‐phase growth conditions. Curli expression is dependent on RpoS, a sigma factor that controls many stationary phase‐inducible genes. Many commonly used K‐12 strains carry an amber mutation in rpoS. Strains able to form Curli carry an amber suppressor whereas curli‐negative E. coli K‐12 strains, in general, are sup°. Introduction of supD, supE, or supF suppressors into sup0 strains resulted in expression of temperature‐regulated curli. In curli‐deficient, RpoS−E. coli K‐12 strains, csgA is transcriptionally activated by mutations in hns, which encodes the histone‐like protein H‐NS. Curli expression, fibronectin binding, and csgA transcription remain temperature‐ and osmoregulated in such double mutants. Our data suggest that RpoS+ strains, and hence curli‐proficient strains of E. coli K‐12, are relieved for the transcriptional repression mediated by the H‐NS protein upon accumulating RpoS as cells reach stationary phase.
Characterization of movement disorders in patients with familial Creutzfeldt-Jakob disease carrying the E200K mutation.

BACKGROUND While myoclonus and ataxia are considered common in patients with familial Creutzfeld-Jakob disease (fCJD), other movement disorders are less prevalent. OBJECTIVES To systemically evaluate the frequency of extrapyramidal signs and movement disorders in patients with fCJD. METHODS A detailed neurological examination, with special emphasis on movement disorders and extrapyramidal signs, was conducted in 43 consecutive symptomatic CJD patients (26 males and 17 females; mean age 58.7 +/- 8.9 yrs, range 43-77 years) carrying the E200K mutation in the PRNPgene. RESULTS Limb or gait ataxia was noted in 38 patients (88%) (37 patients, 86%, had ataxia at presentation). Myoclonus was evident in 25/43 patients (58%) (21 patients, 49%, at presentation). In 95% of the patients (41/43) (37/43, 86% at presentation) at least one extrapyramidal sign throughout the disease course was noted, the most prevalent being rigidity (28/43, 65% of the patients; and 22/43, 51% at presentation), followed by the glabellar sign (24/43, 56% of the patients; and 22/43, 51% at presentation), bradykinesia (19/43, 44%; and 15/43, 35% at presentation), dystonia (15/43, 35%; 12/43, 28% at presentation) and tremor (13/43, 30%; 12/43, 28% at presentation). CONCLUSIONS In this unique population of fCJD patients, myoclonus was less prevalent than previously reported while other extrapyramidal signs were common and occurred at a relatively early stage of the disease. The high prevalence of movement disorders can be added to other phenomena characteristic of this familial disorder among Libyan lews. Whether this is attributable to the E200K mutation itself or to some other mechanism has still to be elucidated.
Can home care maintain an acceptable quality of life for patients with terminal cancer and their relatives?

This prospective study was designed to assess whether patients with terminal cancer, and their relatives, find that competent home care sufficiently maintains comfort and helps adjustment. A random sample from a home care service with readily available beds comprised 77 adults and their relatives who were able and willing to be interviewed separately each week. They were asked the nature and degree of current problems and regular assessments were made of some qualities of life including mood, attitude to the condition, perceived help and preferred place of care. These patients had 90% of their care at home; 29% died at home but 30% were finally admitted for one to three days and 41 % for longer. In the final eight weeks, tolerable physical symptoms were volunteered by a mean of 63% each week and psychological symptoms by 17%. Some distress was felt by 11 % of patients; this was usually from pain, depression, dyspnoea, anxiety or weakness, and generally did not persist. Relatives suffered grief, strain or their own ill health. Patients' and relatives' reports generally matched except for the strain on carers. Regular assessments found that 64% of patients thought death certain or probable, and 27% thought it possible. Various proportions coped by optimism, fighting their disease, partial suppression or denial, but 50% reached positive acceptance. Relatives were more aware and accepting. About three-quarters of patients and half the relatives were composed, often enjoying life. Serious depression affected 5% of patients and anxiety 4%, but relatives' manifest depression in the later stages increased to 17% and anxiety to 14%. Many consciously disguised their feelings. Treatment was usually praised but realistic preference for home care fell steadily from 100% to 54% of patients and 45% of relatives. At follow-up most relatives approved of where patients had received care and died.
Contribuições para o planejamento de parques tecnológicos urbanos

O fenomeno da globalizacao dos mercados, que vem se desenvolvendo de forma acelerada, introduz novas demandas e desafios com relacao a politicas e a mecanismos que promovam a geracao e a disseminacao do conhecimento como base para a competitividade empresarial e o crescimento economico (Albagli, 1999; Cassiolato & Lastres, 1999; Salomao, 1998; Terra, 2000).