Miracle-dz/UniFAR-FTUs huggingface dataset:
Drotrecogin alpha and anticoagulants in septic patients after cardiac surgery.

EDITOR: Drotrecogin alpha (Xigris; Eli Lilly and Company, IN, USA) is a recombinant form of human activated protein C (Fig. 1). It was approved by the Food and Drug Administration in 2001 for the treatment of severe sepsis in adult patients who are at high risk of death [1]. The protein C worldwide evaluation in severe sepsis (PROWESS) trial [2] details that drotrecogin alpha (activated) should be given to patients with septic shock, acute physiology and chronic health evaluation (APACHE) II . 24 and at least one new (,48 h) organ dysfunction, provided there is no risk of bleeding. The absence of a beneficial treatment effect, coupled with an increased incidence of serious bleeding complications, indicates that it should not be used in patients with severe sepsis who are at low risk of death, such as those with single-organ failure or an APACHE II score less than 25. In the recombinant human activated PROWESS study, patients at an increased risk of bleeding were excluded. Nevertheless, the incidence of bleeding with drotrecogin alpha was 3.5% vs. 2% for placebo (P 5 0.06), and these events occurred primarily during the infusion period (2.4% vs. 1%; P 5 0.02). The incidence of serious bleeding was similar for those who received drotrecogin alpha alone and those who also received prophylactic heparin (3.5% vs. 3.7%); however, patients at higher risk of bleeding or with a lower platelet count were less likely to receive heparin prophylaxis. Significant interactions have been noted [3] between heparin and activated protein C promoting bleeding and recommendations have been made to avoid the administration of anticoagulants during the infusion of drotrecogin alpha. These recommendations make it hard to be used in cardiac surgery especially in patients with prosthetic mechanical heart valves or atrial fibrillation. We describe two patients who underwent open-heart surgery and received drotrecogin alpha (activated) for postoperative sepsis. Patient 1
Comprehensive Screening Reveals Strong and Broadly Directed Human Immunodeficiency Virus Type 1-Specific CD8 Responses in Perinatally Infected Children

ABSTRACT Advances in antiviral therapy have dramatically shifted the demographics of pediatric human immunodeficiency virus type 1 (HIV-1) infection in the developed world, and a growing proportion of perinatally HIV-1-infected children are now entering their second or even third decade of life. Although cellular immune responses to HIV are known to be weak in early infancy, the magnitude, breadth, and specificity of responses later in childhood have not been characterized in detail. We performed a comprehensive characterization of HIV-1-specific CD8 responses in 18 perinatally infected children (age range, 6 to 17 years), most of whom were on antiviral therapy, using both previously defined HIV-1 epitopes and overlapping peptides spanning all HIV-1 proteins. Multispecific responses were detected in all subjects and accounted for a median of 0.25 to 0.3% of all peripheral blood mononuclear cells that was similar to the magnitude seen in HIV-infected adults. CD8 responses were broadly directed at an average of 11 epitopes (range, 2 to 27 epitopes) and targeted nearly all HIV-1 proteins, with the highest proportion in Gag. Responses were readily detected even in those children with suppressed viremia on highly active antiretroviral therapy, although the breadth (P = 0.037) and the magnitude (P = 0.021) were significantly lower in these subjects. Each child recognized only a small minority of the HIV-1 optimal epitopes defined for his or her class I HLA alleles. Together, these data indicate that perinatally infected children who survive infancy mount a robust HIV-1-specific CD8 response that is much stronger than previously thought and is comparable in magnitude and breadth to that of adults. Moreover, this response has the potential to be broadened to target more epitopes, making these children attractive candidates for immunotherapeutic interventions.
[Osteometry of the femora in Turkish individuals: a morphometric study in 114 cadaveric femora as an anatomic basis of femoral component design].

OBJECTIVES Clinical and experimental studies of total hip arthroplasty have demonstrated that a close geometric fit between the femoral component and supporting bone is essential for durable implant fixation. Long-term success of total hip prostheses depends on appreciation of the proximal femur anatomy and identification of mean reference values of critical landmarks. Current data on dimensions of prostheses and implantation are based on osteometric measurements of the femora in Western populations. This study was designed to evaluate osteometric features of femora in Turkish individuals and to establish a national database for future studies. METHODS We conducted morphometric measurements of proximal femoral anatomy and its angular configuration on conventional radiograms of 114 cadaveric adult femora of Turkish individuals who did not have any developmental bone abnormality. Measurements were made according to the parameters defined by Noble et al. For comparison, we used morphometric data reported on Western populations by the same investigators. RESULTS Several femoral features were found to be different in Turkish individuals. Although femur head size and offset were similar to Western values, Turkish subjects had a higher femoral head due to valgus position of the femoral head-neck angle, a narrower proximal femoral metaphysis, and a narrower medullary canal with a longer isthmic segment. CONCLUSION Our data revealed diverse features of femoral geometry in Turkish individuals compared to Western populations. These differences should be taken into account in the design and development of hip prostheses.
Efficient transcriptional activation of many simple modular promoters by simian virus 40 large T antigen

Simian virus 40 (SV40) large T antigen is a multifunctional protein which plays central roles during both lytic and transforming infections by SV40. It is a potent transcriptional activator and increases expression from the SV40 late promoter and from several cellular promoters. To understand better the transcriptional activation activity of large T antigen, we examined its ability to transactivate a set of simple modular promoters containing one of four upstream activation sequences coupled with one of three different TATA box sequences originally constructed and studied by Taylor and Kingston (Mol. Cell. Biol. 10:165-175, 1990). Large T antigen activated transcription from all of these simple promoters. The identity of the TATA box was a more important determinant of the final level of gene expression than was the identity of the upstream activating sequence element. We also determined the ability of a set of mutant SV40 large T antigens to activate a subset of these promoters. Several mutant SV40 large T antigens which had reduced ability to activate the complex SV40 late and Rous sarcoma virus long terminal repeat promoters showed reduced transcriptional activation activity on all of the modular promoters tested. We used a set of promoter derivatives of the human U6 small nuclear RNA promoter containing different TATA boxes and found that wild-type large T antigen could activate transcription from all of them, although to widely different levels of expression.
Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity

Purpose of review Lipoprotein(a) is a structurally and functionally unique lipoprotein consisting of the glycoprotein apolipoprotein(a) covalently linked to LDL. Lipoprotein(a) is assembled extracellularly by a two-step mechanism, still incompletely understood, in which initial non-covalent interactions between apolipoprotein(a) and apolipoprotein B precede specific disulfide bond formation. Elevated concentrations of plasma lipoprotein(a) are a risk factor for a variety of vascular diseases, including coronary heart disease, ischaemic stroke and venous thrombosis. Whereas many pathogenic mechanisms have been proposed for lipoprotein(a), it remains to be conclusively demonstrated which mechanisms are relevant to human disease. Recent findings Structural and functional studies have verified that apolipoprotein(a) kringle 4 types 6-8 contain lysine binding sites of a weaker affinity for lysine analogues than kringle 4 type 10. Recent evidence has conclusively shown a role for kringle 4 types 7 and 8 in lipoprotein(a) assembly. Moreover, apolipoprotein(a) has been shown to undergo a conformational change, from a closed to an open form, which accelerates the rate of covalent lipoprotein(a) assembly. Functional studies in vitro have identified the domains in apolipoprotein(a) that mediate its inhibitory effects on fibrin clot lysis, binding to fibrin and other biological substrates, and pro-inflammatory and anti-angiogenic properties. Summary Extensive structure-function studies of apolipoprotein(a) have begun to yield important insights into the domains in apolipoprotein(a) that mediate lipoprotein(a) assembly and the pathogenic effects of this lipoprotein. Continued investigations of these relationships will contribute critically to unravelling the many outstanding questions about lipoprotein(a) metabolism and pathophysiology.
An unusual presentation of pulmonary embolism

Pulmonary embolism (PE) is a common cardiovascular emergency, by which occlusion of a part of the pulmonary arterial bed may lead to acute life threatening but potentially reversible right ventricular failure. Early diagnosis is fundamental to implement immediate effective treatment to reduce mortality. However, the diagnosis can be easily missed due to non-specific clinical presentation. We wish to present an unusual case whereby a patient with no risk factors for PE, symptoms suggestive of acute pericarditis and an ECG showing concave ST segment elevation was found to have multiple pulmonary emboli.
SOME OBSERVATIONS ON THE FINE STRUCTURE OF THE SYNAPSES IN THE OLFACTORY BULB OF THE MOUSE, WITH PARTICULAR REFERENCE TO THE ATYPICAL SYNAPTIC CONFIGURATIONS.

Fine structural features of the synapses observed electron microscopically in the olfactory bulb of the mouse were described with particular reference to atypical characteristics which mainly consisted in the pattern of the distribution of the so-called synaptic vesicles. Five types of these unconventional synapses were identified: a) Synapses between two neuronal processes, where vesicles are distributed on both sides of synaptic junction. b) Synaptic junction between a neuronal process and the mitral cell soma, with apparently same situation of the vesicles as in a-type. c) Morphologically reciprocal or bipolar synaptic junction between two neuronal processes, where one process is either presynaptic or postsynaptic against the other process at different synaptic patches. d) Presynaptic synapses (GRAY 1962) or serial synapses (KIDD 1962). e) Synapses with postsynaptic ‘subsurface cistern’ (ROSENBLUTH 1961) or ‘double membrane’ (ENGSTROM 1958) or ‘formation sous synaptique’ (TAXI 1961). Physiological implications of these unconventional or atypical synaptic junctions were briefly discussed.
A comparative evaluation of in vitro growth inhibitory activities of different solvent extracts of some medicinal plants in Northern Ghana against selected human pathogens

Bacterial resistance to conventional antibiotics justifies the need to explore alternative remedies from medicinal plants since they represent a rich source of antimicrobial agents. We present a comparative evaluation of in vitro antibacterial activities of different solvent extracts of seven medicinal plants used to treat bacterial infections amongst the tribes of Northern Ghana. In the present study, extracts of the plants were obtained using solvents of different polarities and their growth inhibitory activity against Salmonella typhi and Escherichia coli evaluated in vitro. Phytochemical screening revealed the presence of alkaloids, saponins, tannins, coumarins and flavonoids in most of the extracts. These secondary metabolites have been implicated as antibacterial agents in several reports. The extracts from the seven plants showed varied antibacterial activity against the test organisms. Of the bacteria tested, Salmonella typhi was the least susceptible to most of the extracts. The ethanol extracts of the plants generally demonstrated superior growth inhibitory activity at 100 and 200mg/ml concentrations while the aqueous extracts were the least active at similar concentrations. The maximum antibacterial activity was recorded for Khaya senegalensis ethanol stem bark extract against Escherichia coli (zone of inhibition = 20.10mm) and Salmonella typhi (zone of inhibition = 17.10mm) at 200mg/ml. The result presents the basis for which these plants have been used for treatment of bacterial infections in folkloric medicine. The results further reveal that ethanol stem bark extract of K. senegalensis demonstrated the greatest activity and thus can be very useful in the search for novel antibacterial agents.
Critical genre analysis and professional practice: the case of public contests to select professors for Brazilian public universities

Several approaches have been applied to the analysis of language at work, among them, the ergologic (LACOSTE, 1998; NOUROUDINE, 2002), the interactional-sociolinguistic (DREW, HERITAGE, 1992), and the genre-based (BAZERMAN; PARADIS, 1991). In this article, focusing on the latter approach, I discuss the reasons and methods for analyzing professional genres. Particularly, I center my attention on the approach which, more recently, has been called critical genre analysis (BHATIA, 2004, 2007, 2009; MOTTA-ROTH, 2008). As part of the theoretical reflection undertaken, I also present an introductory analysis of genres involved in the social practice of public contests for professor positions at Brazilian universities. These examinations not only exemplify a kind of problematic relation between language and work, but they constitute an excellent example to illustrate a Critical Genre Analysis (CGA).
Multicenter Stratified Comparison of Hospital Costs Between Laparoscopic and Open Colorectal Cancer Resections: Influence of Tumor Location and Operative Risk

Objective: To compare actual 90-day hospital costs between elective open and laparoscopic colon and rectal cancer resection in a daily practice multicenter setting stratified for operative risk. Background: Laparoscopic resection has developed as a commonly accepted surgical procedure for colorectal cancer. There are conflicting data on the influence of laparoscopy on hospital costs, without separate analyses based on operative risk. Methods: Retrospective analyses using a population-based database (Dutch Surgical Colorectal Audit). All elective resections for a T1-3N0-2M0 stage colorectal cancer were included between 2010 and 2012 in 29 Dutch hospitals. Operative risk was stratified for age (<75 years or ≥75 years) and ASA status (I-II/III-IV). Ninety-day hospital costs were measured uniformly in all hospitals based on time-driven activity-based costing. Results: Total 90-day hospital costs ranged from &OV0556;10474 to &OV0556;20865 in the predefined subgroups. For colon cancer surgery (N = 4202), laparoscopic resection was significant less expensive than open resection in all subgroups, savings because of laparoscopy ranged from &OV0556;409 (<75 years ASA I-II) to &OV0556;1932 (≥75 years ASA I-II). In patients ≥75 years and ASA I-II, laparoscopic resection was associated with 46% less mortality (P = 0.05), 41% less severe complications (P < 0.001), 25% less hospital stay (P = 0.013), and 65% less ICU stay (P < 0.001). For rectal cancer surgery (N=2328), all laparoscopic subgroups had significantly higher total hospital costs, ranging from &OV0556;501 (<75 years ASA I-II) to &OV0556;2515 (≥75 years ASA III-IV). Conclusions: Laparoscopic resection resulted in the largest cost reduction in patients over 75 years with ASA I-II undergoing colonic resection, and the largest cost increase in patients over 75 years with ASA III-IV undergoing rectal resection as compared with an open approach.
Design of a coplanar waveguide-to-ridge gap waveguide transition via capacitive coupling

A transition from Coplanar Waveguide (CPW) via capacitive coupling in order to provide feeding to the so-called Ridge Gap Waveguide (RGW) has been investigated. The main objective of this work is to find a way to facilitate integration of active electronics with the gap waveguide structure and also to do measurements of the components made in gap waveguide technology working around 100 GHz. The transition design and simulation of S parameters for the designed topology is presented.
A Polymorphic Locus Near the Human Insulin Gene Is Associated with Insulin-dependent Diabetes Melliitus

A polymorphic region flanking the human insulin gene on the short arm of chromosome 11, the insulin-gene-linked DNA polymorphism, can be described as a locus with at least three classes of alleles: a common small “class 1” allele averaging 570 base pairs, a rare intermediate “class 2” allele of about 1320 base pairs, and a large “class 3” allele averaging 2470 base pairs in size. We have determined the genotype at this locus of 393 unrelated diabetic and nondiabetic individuals. Differences were observed in the genotypie and allelic frequencies between groups of different races. Asians [17 nondiabetic, 2 with insulin-dependent diabetes mellitus (IDDM), and 8 with non-insulin-dependent diabetes mellitus (NIDDM)] exhibited the least variation in the size of this locus and 98% of the alleles in this group were class 1. A group of American blacks (32 nondiabetic, 5 with IDDM, and 40 with NIDDM) exhibited considerable variation in the size of this locus, and about 22% of the individuals examined had a genotype that included a rare class 2 allele. In neither of these two racial groups were the genotypie or allelic frequencies different between the nondiabetic and diabetic segments of these groups. However, in a group of Caucasians (83 nondiabetic, 113 with IDDM, and 76 with NIDDM), there was a significantly higher frequency of class 1 alleles and genotypes containing two class 1 alleles in the diabetic patients compared with nondiabetic controls. A strikingly higher frequency of class 1 alleles (P < 0.0001) and genotypes containing two class 1 alleles (P < 0.0001) was observed in the IDDM group compared with nondiabetic Caucasians, whereas the difference between NIDDM and controls was only near the level of statistical significance (P = 0.025). Analysis of the combined data of our Caucasian population and those reported from studies of Caucasians from Denmark and St. Louis, Missouri, continued to show an increased frequency of class 1 alleles and genotypes containing two class 1 alleles in the IDDM group (P = 0.0001) compared with the nondiabetic group; however, there were no longer differences in genotypic or allelic frequencies between NIDDM and nondiabetic groups.
Response of Rabbit Achilles Tendon to Chronic Repetitive Loading

The objective of this work was to assess the response of tendon to chronic repetitive loading. Controlled muscle stimulation was used to load the rabbit Achilles tendon at a frequency of 1.25 Hz for two hours per day, three days per week for a period of 11 weeks. Average peak tendon force was 26 N during the protocol. The loading protocol did not modify the gross morphology of the tissue, nor its water content or cellularity. Increases in mRNA expression of collagen Type III and MMPs were observed, but no signs of injury were detected by histologic examination of tendon and paratenon structures. The lack of a detectable injury response suggests that the tendons were not loaded beyond their capacity for repair. Factors additional to mechanical loading such as aging, illness or stress may be necessary to produce pathology.
Neonatal Sevoflurane Exposure Induces Adulthood Fear-induced Learning Disability and Decreases Glutamatergic Neurons in the Basolateral Amygdala

Background: Neonatal mice exposed to sevoflurane show certain cognitive and behavioral impairments in adulthood. However, the mechanisms underlying long-term cognitive deficits induced by sevoflurane exposure remain unknown. The present study was performed to investigate whether there is differential neuronal activation between naive mice and sevoflurane-exposed neonates in fear-conditioning tests based on immediate early gene (c-Fos) expression. Methods: Male mice were exposed to 3% sevoflurane (SEVO group) or carrier gas alone (no anesthesia, NA group) for 6 hours on postnatal day 6. The mice were allowed to mature before performing the contextual fear-conditioning test. A reduced freezing response was confirmed in the SEVO group. Neural activation in the regions of the medial prefrontal cortex, hippocampus, and amygdala was investigated using c-Fos immunostaining 2 hours after the test. The types of neurons activated were also identified. Results: The number of c-Fos-positive cells decreased by 27% in the basolateral amygdala in the SEVO group, while no significant changes were observed in other regions. Furthermore, glutamatergic, but not &ggr;-aminobutyric acid (GABA)ergic, neurons expressed c-Fos after the contextual fear-conditioning test in both groups. The number of glutamatergic neurons in the basolateral amygdala in the SEVO group was reduced by 27%. Conclusions: Decreased neural activation in the basolateral amygdala may be associated with reduced freezing time in neonatal sevoflurane-exposed mice. Fewer glutamatergic neurons responding to fear stimuli in the basolateral amygdala may contribute to decreased neural activation and learning deficits in mice exposed to sevoflurane as neonates.
Comparison of Titanium and Robinson Stainless Steel Stapes Piston Prostheses

Objective: Although stainless steel stapes prostheses have generally been considered magnetic resonance imaging safe, there is concern that this may change with the development of more powerful imaging systems. The objective of the study was to determine whether a titanium piston stapes prosthesis would be audiometrically and surgically equivalent to a Robinson stainless steel piston for stapedectomy. Study Design: Retrospective chart review. Setting: Private otology practice. Patients: In all, 50 patients underwent stapedectomy with a Gyrus titanium piston prosthesis. These patients were matched on the basis of age and preoperative bone-conduction scores with patients who underwent stapedectomy with a Robinson stainless steel piston prosthesis. Main Outcome Measures: Audiometric results are analyzed, and surgical complications noted. Results: There was no significant difference between groups in hearing improvement or postoperative air-bone gap. The mean four-frequency hearing improvement was 27.7 dB for the stainless steel group and 27.8 dB for the titanium group. The mean postoperative air-bone gap was 2.65 dB for the stainless steel group and 2.60 for the titanium group. Neither group had a surgical complication. Conclusion: The titanium stapes prosthesis is a good alternative to a stainless steel prosthesis.