Significant changes in combined consistent biomarkers and CTAngiography revealed during an interval of 6months before abdominal aortic aneurysm rupture.
The most commonly used predictor of rupture of abdominal aortic aneurysm (AAA) is the diameter, but this does not correlate well with the risk of rupture. Therefore, in order to make further improvements in clinical decisions regarding AAA patients, the development of additional predictive tools other than aneurysm size alone is needed. We herein report a case of a 72-year-old man with AAA that underwent rupture transformation during six months. We review the morphological features changes detected by computed tomography and also observe several alters circulating biomarkers at the same time. In the study presented essentially an association of those combined parameters with the risk of AAA impending rupture.


A dosimetric evaluation of water equivalent phantoms for kilovoltage x-ray beams.
Solid phantoms are widely used in radiation therapy for both relative and reference dosimetry. Two water equivalent phantoms, RMI-457 Solid Water and Plastic Water, were evaluated for use in kilovoltage x-ray dosimetry in the energy range from 75 to 300 kVp. Relative and reference dosimetry measurements were performed in the solid phantoms and compared with water. The results indicate that RMI-457 Solid Water could be used for output factor determination for all energies tested and the measurement of percentage depth doses for the 300 kVp x-ray beam, with data agreeing to within 1%, compared to the same measurements in water. For the same criteria, Plastic Water could only be used for output factor determination of the 300 kVp x-ray beam. The superior agreement of the calculated mass-energy absorption coefficients for Solid Water and water, as compared to Plastic Water and water was consistent with the experimental results. Reference dosimetry is not recommended with the solid phantoms for the energies studied due to the lack of published correction factors. It is recommended that any solid phantom be tested by comparison with water in the same manner before being used for the dosimetry of kilovoltage x-ray beams.


Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins.
An intact alternative pathway of complement activation was assembled from six isolated proteins present at their respective physiological concentrations (C3, 1200 microgram/ml: factor B, 200 microgram/ml; factor D, 2 microgram/ml; beta1H, 560 microgram/ml; C3b inactivator, 34 microgram/ml; and native properdin, 20 microgram/ml). Initiation of the pathway required the presence of five of these proteins not including properdin. The initial C3 convertase of the system was shown to be a fluid-phase rather than a surface-bound enzyme. The ability of the pathway to discriminate between activator and nonactivator was found to reside in the bound C3b molecule. When bound to the surface of an activator through its labile binding site, C3b interacts with surface structures of the activator through another site on the molecule. This interaction results in diminished beta1H binding to C3b and thereby allows the bound C3b molecule to escape control and participate in C3 convertase formation. Thus, initiation of the alternative pathway is a two-step process, the first being non-specific and the second being discriminatory.


Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38).
Dual antiplatelet therapy with aspirin and clopidogrel is standard for prevention of thrombotic complications of percutaneous coronary intervention (PCI). Prasugrel is a thienopyridine that is more potent, more rapid in onset, and more consistent in inhibition of platelets than clopidogrel. TRITON-TIMI 38 is designed to compare prasugrel with clopidogrel in moderate to high-risk patients with acute coronary syndrome (ACS). TRITON-TIMI 38 is a phase 3, randomized, double-blind, parallel-group, multinational, clinical trial. Approximately 13,000 patients with moderate to high-risk ACS undergoing PCI (9500 unstable angina/non-ST-segment elevation myocardial infarction [MI], 3500 ST-segment elevation MI) will be randomized to prasugrel 60 mg loading dose followed by 10 mg daily or clopidogrel 300 mg loading dose followed by 75 mg daily for up to 15 months. The primary end point is the time of the first event of cardiovascular death, MI, or stroke. Analyses will be performed first in the unstable angina/non-ST-segment elevation MI cohort and, conditionally, on the whole ACS population. Major safety end points include TIMI major and minor bleeding unrelated to coronary artery bypass graft surgery. TRITON-TIMI 38 is a phase 3 comparison of prasugrel versus clopidogrel in patients with moderate to high-risk ACS undergoing PCI. In addition, it is the first large-scale clinical events trial to assess whether a thienopyridine regimen that achieves a higher level of inhibition of platelet aggregation than the standard therapy results in an improvement in clinical outcomes.


Trauma and Hypothermia in Antarctica: An Emergency Medicine Marine Simulation Scenario.
Simulation has been shown to improve both learner knowledge and patient outcomes. Many emergency medicine training programs incorporate simulation into their curricula to provide learners with experiences that are rare to encounter in practice, yet performance with a high degree of competence is critical. One rare encounter, which is depicted in the report, is the management of a trauma patient who was hypothermic after falling from an expedition vessel into the cold Southern Ocean. The unique scenario presented in this technical report incorporates CanMEDS learning objectives including the communicator, health advocate, and collaborator roles. Using medical simulation facilities, marine performance simulation facilities, and a video, this scenario provides teaching that is uncommon in traditional emergency medicine training. As such, it is valuable for trainees who intend to practice rural, remote, or expedition medicine, or provide coverage for ships and marine installations.


Frugal Imaging Technique of Capillary Flow through Three-Dimensional Polymeric Printing Powders.
The development of novel imaging techniques of molecular and colloidal transport, including nanoparticles, is an area of active investigation in microfluidic and millifluidic studies. With the advent of three-dimensional (3D) printing, a new domain of materials has emerged, thereby increasing the demand for novel polymers. Specifically, polymeric powders, with average particle sizes on the order of a micron, are experiencing a growing interest from academic and industrial communities. Controlling material tunability at the mesoscopic to microscopic length scales creates opportunities to develop innovative materials, such as gradient materials. Recently, a need for micron-sized polymeric powders has been growing, as clear applications for the material are developing. Three-dimensional printing provides a high-throughput process with a direct link to new applications, driving investigations into the physio-chemical and transport interactions on a mesoscale. The protocol that is discussed in this article provides a non-invasive technique to image fluid flow in packed powder beds, providing high temporal and spatial resolution while leveraging mobile technology that is readily available from mobile devices, such as smartphones. By utilizing a common mobile device, the imaging costs that would normally be associated with an optical microscope are eliminated, resulting in a frugal-science approach. The proposed protocol has successfully characterized a variety of combinations of fluids and powders, creating a diagnostic platform for quickly imaging and identifying an optimal combination of fluid and powder.


[Intraductal ultrasonography for the selection of self expandable metal stent in extrahepatic bile duct carcinoma].
Endoscopic stent insertion with self expandable metal stent (SEMS) is one of the standard palliative treatments for the patients with unresectable bile duct carcinoma. The aim of this study was to determine whether detection of longitudinal spread of extrahepatic bile duct carcinoma by intraductal US (IDUS) would be helpful in the selection of metal stent for the palliative drainage in bile duct carcinoma. Seventeen patients with histologically proven unresectable extrahepatic bile duct carcinoma who underwent endoscopic retrograde cholangiography with IDUS were included. Longitudinal cancer extension along the bile duct was determined and, then, compared with the cholangiographic image. The type and length of SEMS was selected based on IDUS findings. IDUS demonstrated more extensive tumor spread than ERC in 7 of 17 (41.2%) patients with the hepatic side of strictures and in 7 of 16 (43.8%) patients with the duodenal side of strictures. Five of 17 (29.4%) patients have changed the plan of endoscopic biliary drainage with SEMS after IDUS. There was no early dysfunction associated with endoscopic biliary drainage. IDUS prior to biliary drainage would be useful in demonstrating longitudinal extension of extrahepatic bile duct carcinoma. It has a potential role in helping stent selection and identifying factors which predict early stent dysfunction.


Changing patterns of infectious diseases in children during the COVID-19 pandemic.
Each infectious disease has had its own epidemic pattern and seasonality for decades. However, public health mitigation measures during the coronavirus disease 2019 (COVID-19) pandemic have resulted in changing epidemic patterns of infectious diseases. Stringent measures resulted in low incidences of various infectious diseases during the outbreak of COVID-19, including influenza, respiratory syncytial virus, pneumococcus, enterovirus, and parainfluenza. Owing to the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and subsequent immunity development, decreasing virulence of SARS-CoV-2, and worldwide immunization against SARS-CoV-2 in children beyond 6 months of age, mitigation measures are lifted country by country. Consequently, the immunity debt to infectious respiratory viruses other than SARS-CoV-2 contributed to the "off-season," "see-saw," and "upsurge" patterns of various infectious diseases in children. Moreover, apart from the persistence of SARS-CoV-2, the coexistence of other circulating viruses or bacterial outbreaks may lead to twindemics or tripledemics during the following years. Therefore, it is necessary to maintain hand hygiene and immunization policies against various pathogens to alleviate the ongoing impact of infectious diseases on children.


Remote complications of spilled gallstones during laparoscopic cholecystectomy: causes, prevention, and management.
In the last 11 years (November 1989-December 2000), 5526 laparoscopic cholecystectomies were performed in a community residency training program. Two cases (0.04%) of remote complications secondary to spilled gallstones were identified. A 75-year-old woman presented with a sterile abscess in the abdominal wall containing gallstones 4 years and 4 months after an elective laparoscopic cholecystectomy. The second patient, a 43-year-old woman, presented with a subdiaphragmatic/subhepatic abscess containing gallstones. The abscess grew the same bacteria that were present 2 years and 3 months previously during a laparoscopic cholecystectomy for acute gangrenous cholecystitis. In both cases, pigmented gallstones were identified. Causes of gallstone spillage, means of prevention, and ways of managing this complication are discussed.


What can family medicine practices do to facilitate knowledge management?
Family medicine practices face increasing demands to enhance efficiency and quality of care. Current solutions propose major practice redesign and investment in sophisticated technology. Knowledge management (KM) is a process that increases the capacity of a practice to deliver effective care by finding and sharing information and knowledge among practice members or by developing new knowledge for use by the practice. Our preliminary research in family medicine practices has suggested improved patient outcomes with greater and more effective KM. Research in other organizational settings has suggested that KM can be facilitated by certain organizational characteristics. To identify those organizational characteristics within a family medicine practice that management can effect to enhance KM. We performed a cross-sectional secondary analysis of second-year data from 13 community family medicine practices participating in a practice improvement project. Practice KM, leaderships' promotion of participatory decision making, existence of activities supportive of human resource processes, and effective communication were derived from clinician's, nurses', and staff's responses to a survey eliciting responses on practice organizational characteristics. Hierarchical linear modeling examined relationships between individual practice members' perception of KM and organizational characteristics of the practice, controlling for practice covariates (solo-group, electronic medical record use, and perception of a chaotic practice environment) and staff-level covariates (gender, age, and role). Practices with greater participatory decision making and human resources' processes and effective communication significantly (p < .019, p < .0001, and p < .004) increased odds of reporting satisfactory KM (odds ratio = 2.48, 95% confidence interval = 1.32-4.65; odds ratio = 10.84, 95% confidence interval = 4.04-29.12; and odds ratio = 4.95, 95% confidence interval = 2.02-12.16). The sizes of these effects were not substantially changed even when practice members perceived their practice environment as more chaotic. Steps to facilitate KM should be considered when evaluating more intensive and costly organizational solutions for enhancing family medicine practice performance.


Effect of maternal and postweaning folic acid supplementation on global and gene-specific DNA methylation in the liver of the rat offspring.
Intrauterine and early-life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use, and periconceptional supplementation. We investigated the effect of maternal and postweaning folic acid supplementation on DNA methylation in the rat offspring. Female rats were placed on a control or folic acid-supplemented diet during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or supplemented diet for 11 weeks. At weaning, maternal folic acid supplementation significantly decreased global (p < 0.001) and site-specific DNA methylation of the Ppar-γ, ER-α, p53, and Apc genes (p < 0.05) in the liver. At 14 weeks of age, postweaning, but not maternal, folic acid supplementation significantly decreased global DNA methylation (p < 0.05). At 14 weeks of age, both maternal and postweaning folic acid supplementation significantly increased DNA methylation of the Ppar-γ, p53, and p16 genes (p < 0.05) whereas only postweaning FA supplementation significantly increased DNA methylation of the ER-α and Apc genes (p < 0.05). Our data suggest that maternal and postweaning folic acid supplementation can significantly modulate global and gene-specific DNA methylation in the rat offspring. The functional ramifications of the observed DNA methylation changes need to be determined in future studies.


Ossified adamantinous type craniopharyngiomas. A series of 13 patients.
Thirteen patients admitted to hospital mainly with visual disturbances (100%), retarded growth (39%) and diabetes insipidus (23%) were all diagnosed as ossified adamantinous craniopharyngioma. Tumour size was found to be large in all patients. Localization displayed a heterogenous dissemination; 8% intra-suprasellar, 69% suprasellar-extraventricular, 15% extra-intraventricular, and 8% in the suprasellar region extending bilaterally to the frontal and temporal lobes. During the early postoperative period, four patients died with hypothalamic deterioration. Three patients underwent a second operation in view of recurrence, and one died from an infection. Thus, the postoperative survival rate was 62%. All the patients who survived continued to have visual disturbances, but only one deteriorated. Five patients exhibited diabetes insipidus during the postoperative period, among them 4 after surgical intervention and 5 patients displayed panhypothyroidism, three of them after surgery. Consequently, it is confirmed by the present review that craniopharyngiomas still offer a potential dilemma in their management. Difficulties caused by adhesion or invasion of ossified craniopharyngiomas and thus the increase in morbidity and mortality during surgical intervention and in the postoperative period are discussed.


Exciton transfer in quantum dot arrays: comparison of eigenbasis and site basis representations.
We discuss differences between eigenbasis and site basis representations for models of exciton transfers in an array of quantum dots. The exciton relaxation processes are well described by the master equation in the eigenbasis representation. The site basis evolution equation up to the second order of the interdot interaction is straightforwardly derived from the eigenbasis equation by using perturbation theory when the interaction is sufficiently small compared to the energy difference between the exciton states in each quantum dot. Although the higher order site basis equations can be derived similarly, the resultant equations are too complicated to use in the actual calculations. The master equation in the eigenbasis representation has several advantages over the site basis one: (i) the system described in terms of the eigenbasis representation can evolve into thermal equilibrium because the equation satisfies the detailed balance, (ii) the site basis equation does not reasonably describe the exciton state trapped in a local energy minimum at very low temperature, and (iii) it is computationally less demanding to carry out the eigenbasis evolution equation.


Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR.
Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells are capable of counteracting these signals through mechanisms that are largely unknown. Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR. PHD3 silencing in human gliomas or genetic deletion in a murine high-grade astrocytoma model markedly promotes tumour growth and the ability of tumours to continue growing under unfavourable conditions. The growth-suppressive function of PHD3 is independent of the established PHD3 targets HIF and NF-κB and its hydroxylase activity. Instead, loss of PHD3 results in hyperphosphorylation of epidermal growth factor receptor (EGFR). Importantly, epigenetic/genetic silencing of PHD3 preferentially occurs in gliomas without EGFR amplification. Our findings reveal that PHD3 inactivation provides an alternative route of EGFR activation through which tumour cells sustain proliferative signalling even under conditions of limited oxygen availability.


Ethnic diversity: South Asian ethnicity is associated with increased coronary artery bypass grafting mortality.
South Asian ethnicity might result in a higher atherosclerotic vascular risk compared with white ethnicity. However, the effect of South Asian ethnicity on clinical outcomes after cardiac surgery is unknown. Thus, we determined whether South Asian ethnicity is a predictor of a poorer outcome after coronary artery bypass grafting. We examined data from 6177 South Asian and white patients who underwent coronary artery bypass grafting at the Toronto General Hospital from January 1994 through June 2003 and used propensity score matching techniques to analyze 917 patients from each group in more detail. Patients were matched for age, sex, body surface area, left ventricular ejection fraction, New York Heart Association class, previous cardiac surgery, number of diseased vessels, and other factors. Independent predictors of operative morbidity and mortality were determined by means of multivariate logistic regression. Overall operative mortality was 1.8%. Mortality was higher in South Asian patients than in white patients (2.5% vs 1.1%, P = .02). Postoperative morbidity (eg, myocardial infarction, sepsis, sternal wound infection, postoperative hospital stay, and use of inotropes) also was higher in the South Asian group. In addition to the standard independent predictors of mortality, South Asian ethnicity was an independent predictor of mortality (odds ratio, 3.1; 95% confidence interval, 1.4-6.8). These data indicate that South Asian ethnicity per se is an independent predictor of a poorer outcome after coronary artery bypass grafting and suggest that ethnicity is a cardiovascular risk factor that should be considered when assessing clinical outcomes preoperatively before coronary artery bypass grafting or other interventional revascularization procedures.


Increase in calcium binding activity in renal cortex of rats treated with stannous chloride.
The effect of tin on the calcium binding activity in renal cortex was studied in rats administered stannous chloride intraperitoneally. The calcium concentration in the soluble fraction of renal cortex was elevated about 30-fold over that in controls 2 days after administration of tin (3.0 mg/100 g). The calcium binding activity in the soluble fraction of renal cortex increased significantly at any of the time intervals between 6 and 72 hr after administration of tin, and this increase preceded an elevation of the calcium concentration in the renal cortex. The increased calcium binding activity produced by administration of tin was strikingly reduced by treatment with actinomycin D (100 microgram/100g). A significant increase in calcium binding activity was not exhibited after administration of zinc, manganese, calcium, or lead. These results suggest that the calcium accumulation in the renal cortex caused by administration of tin is closely connected with an increase in calcium binding activity.


Apolipoprotein C-I Levels Are Associated with the Urinary Protein/Urinary Creatinine Ratio in Pediatric Idiopathic Steroid-Sensitive Nephrotic Syndrome: A Case Control Study.
Humoral factors may cause idiopathic steroid-sensitive nephrotic syndrome (ISSNS). In the present study, we analyzed serum proteins using mass spectrometry (MS) to identify proteins associated with the pathophysiology of pediatric ISSNS. We collected serial serum samples from 33 children during each ISSNS phase; Phase A1 is the acute phase prior to steroid treatment (STx), Phase A2 represents the remission period with STx, and Phase A3 represents the remission period after completion of STx. Children with normal urinalyses (Group B) and children with a nephrotic syndrome other than ISSNS (Group C) served as controls. No significant differences in urinary protein/urinary creatinine (UP/UCr) ratios were observed between the children with phase A1 ISSNS and Group C. We used surface-enhanced laser desorption/ionization time of flight MS for sample analysis. Four ion peaks with a mass-to-charge ratio (m/z) of 6,444, 6,626, 8,695, and 8,915 were significantly elevated during ISSNS Phase A1 compared to Phase A2, Phase A3, and Group C. The intensity of an m/z of 6,626 significantly correlated with the UP/UCr ratio and an m/z of 6,626 was identified as apolipoprotein C-I (Apo C-I). Apo C-I levels correlate with the UP/UCr ratio in pediatric ISSNS. Our findings provide new insights into the pathophysiology of ISSNS.


An unusual cause of a penetrating injury to the anterior urethra: a thorny situation.
Concurrent penetrating injury to the male external genitalia and the anterior urethra is uncommon. This case illustrates an unusual cause of such an injury, and its subsequent management and outcome. A 69-year-old man had his scrotum and anterior urethra pierced by a long thorn when he fell in his farm. He presented with urine leakage from the scrotal wound each time he micturated. Cystoscopic examination confirmed the cause and extent of the injury, and also facilitated the extraction of the thorn. The injury was allowed time to heal by urinary diversion with a urinary catheter. There were no stricture or fistula formations and the patient remained symptom-free at 3 months follow-up. Careful cystoscopic examination was both diagnostic and therapeutic in this case. A conservative approach is a feasible option in the management of selected cases of penetrating anterior urethral injury.


[Cutaneous hyperpigmentation of the distal falanx in a newborn].
A case of distal falangeal hyperpigmentation in a 2-month female newborn, who did not show any other cutaneous disease at the time of our observation, is presented. The aim of our study is to focus attention on this condition, actually considered a benign, asymptomatic, transitory manifestation, rarely reported in literature. On the basis of the clinical features, it has been proposed to add this pigmentation to the transient benign dermatoses of newborns.


Harnessing the power of optical microscopy for visualization and analysis of histopathological images.
Histopathology is the foundation and gold standard for identifying diseases, and precise quantification of histopathological images can provide the pathologist with objective clues to make a more convincing diagnosis. Optical microscopy (OM), an important branch of optical imaging technology that provides high-resolution images of tissue cytology and structural morphology, has been used in the diagnosis of histopathology and evolved into a new disciplinary direction of optical microscopic histopathology (OMH). There are a number of ex-vivo studies providing applicability of different OMH approaches, and a transfer of these techniques toward in vivo diagnosis is currently in progress. Furthermore, combined with advanced artificial intelligence algorithms, OMH allows for improved diagnostic reliability and convenience due to the complementarity of retrieval information. In this review, we cover recent advances in OMH, including the exploration of new techniques in OMH as well as their applications, and look ahead to new challenges in OMH. These typical application examples well demonstrate the application potential and clinical value of OMH techniques in histopathological diagnosis.


Morphology, ultrastructure, and bacteriophage infection of the helical mycoplasma-like organism (Spiroplasma citri gen. nov., sp. nov.) cultured from "stubborn" disease of citrus.
The mycoplasma-like organism Spiroplasma citri gen. nov., sp. nov., isolated from citrus infected with "Stubborn" disease and carried in serial cultures in several media, was examined by dark-field microscopy and electron microscopy of negatively-stained and shadowed preparations and of sections. It grows as motile, helical filaments in liquid, but as nonmotile, nonhelical filaments and round bodies in agar cultures. Helicity and motility are lost in old broth cultures and upon addition of a variety of negative stains, fixatives, and other solutions. No organelles accounting for motility are present, but a layer of surface projections is present on the surface of the single, bounding membrane. The mycoplasma produces a tailed, type B bacteriophage which appear to attach to the outer layer. Helical filaments are preserved in ammonium molybdate, but not in sodium phosphotungstate, and by fixation in Formalin or glutaraldehyde made up in medium, but not by osmium nor by glutaraldehyde in cacodylate buffer. This mycoplasma appears similar to the noncultured helical microorganism in corn stunt-diseased tissues and is probably a representative of a new group of mycoplasmas which are in possession of surface projections, rotary motility, and bacteriophage infection.


Germabenzenylpotassium: A Germanium Analogue of a Phenyl Anion.
Reduction of the stable germabenzene, 1-Tbt-2-tert-butyl-germabenzene (Tbt=2,4,6-tris[bis(trimethylsilyl)methyl]phenyl), with KC8 resulted in the formation of 2-tert-butylgermabenzenylpotassium, that is, the germanium analogue of phenylpotassium, under concomitant elimination of the aryl group from the Ge atom. Under an inert atmosphere, this germabenzenylpotassium could be isolated in the form of stable yellow crystals. In the crystalline state, as well as in solution, the germabenzenyl moiety adopts a monomeric form, even though the X-ray diffraction analysis suggests the presence of highly reactive Ge=C double bonds. The spectroscopic and X-ray crystallographic analyses, in combination with theoretical calculations indicate an ambident character for this germabenzenyl anion, with contributions from aromatic and germylene resonance structures.


Membrane plasma exchange in Goodpasture's syndrome.
We report two cases with Goodpasture's syndrome successfully treated by membrane plasma exchange. In both patients, pulmonary infiltrations and hemoptysis had already resolved after the first pulse methylprednisolone dose (1000 mg IV). Following plasma exchange, renal function did not further deteriorate in one patient and returned to normal in the other patient. From the clinical course of our patients and a review of the literature, we conclude that membrane plasma exchange is effective in preventing deterioration of renal function in Goodpasture's syndrome. Analysis of the literature shows that patients who respond to plasma exchange have significantly fewer crescents and lower plasma creatinine, while non-responders are more often oliguric or anuric and require dialysis at the time of plasma exchange.


[Cloning and expression of lipase gene to enantioselective resolution of (S)-ketoprofen].
We screened a strain NK13 for a certain extent asymmetric hydrolysis the rac-ketoprofen Chloroethyl ester to (S)-Ketoprofen. As identified, NK13 was Bacillus megaterium. Digested NK13 genomic DNA with Sau3AI partially and recovered the fragment from 2 kb to 6 kb, cleaved the plasmid of pUC18 with BamH I, ligated the 2-6 kb fragment of NK13 genomic DNA into pUC18 plasmid, and then transformed an Escherichia coli strain DH5alpha. We created the gene library of NK13 and obtained a positive clone, pUC-NK1 in the library from the tributyrin flat. The result of sequencing showed that there was a whole open read frame (ORF) of 633 bp lipase gene in the plasmid of pUC-NK1. To compare with the genes of GenBank, this lipase gene was reported firstly (GenBank Accession No. EU381317). The lipase gene was amplified by PCR, using pUC-NK1 plasmid as template, and subcloned into the high expression vector pET21b(+) under the control of T7 promoter. The recombinant plasmid, pET-NKest1, was then transformed into an Escherichia coli strain BL21 (DE3) for the production of recombinant lipase protein. After 3 hours of induction by isopropyl-beta-D-thiogalactoside (IPTG), lipase was expressed. SDS-PAGE analysis showed that the relative molecular mass of the lipase protein was about 20 kDa. The result of high performance liquid chromatography (HPLC) showed that the conversion rate of the recombinant strain was fifty times than the wild strain NK13's. The (S)-Ketoprofen enantiomeric excess of the recombinant strain was 75.28%, which indicated that the lipase could hydrolyze (S)-Ketoprofen Chloroethyl ester firstly. If we research the conditions of the hydrolysis rac-ketoprofen Chloroethyl ester of this lipase further, maybe it could offer a foundation to product (S)-Ketoprofen industrially.


Brucella arthritis of the knee, 1 year after revision of anterior cruciate ligament reconstruction.
Brucellosis is a zoonotic infection with a broad spectrum of clinical manifestations. The authors report the first case in the literature of septic arthritis of the knee 1 year after revision of anterior cruciate ligament reconstruction. Brucella melitensis biotype 3 was found in both synovial fluid and blood cultures. The patient was treated initially with arthroscopic debridement. After the diagnosis was confirmed, a second arthroscopic lavage and metal work removal was applied leaving the graft in place. Antimicrobial chemotherapy was prescribed for 3 months. The infection was fully eradicated and the patient is still asymptomatic, 4 years after the treatment.


Bacteroides fragilis synthesizes a DNA invertase affecting both a local and a distant region.
The activity of a fourth conserved tyrosine site-specific recombinase (Tsr) of Bacteroides fragilis was characterized. Its gene, tsr19, is adjacent to mpi, encoding the global DNA invertase regulating capsular polysaccharide biosynthesis. Unlike the other described Tsrs of B. fragilis, Tsr19 brings about inversion of two DNA regions, one local and one located distantly.


CANDI: an R package and Shiny app for annotating radiographs and evaluating computer-aided diagnosis.
Radiologists have used algorithms for Computer-Aided Diagnosis (CAD) for decades. These algorithms use machine learning with engineered features, and there have been mixed findings on whether they improve radiologists' interpretations. Deep learning offers superior performance but requires more training data and has not been evaluated in joint algorithm-radiologist decision systems. We developed the Computer-Aided Note and Diagnosis Interface (CANDI) for collaboratively annotating radiographs and evaluating how algorithms alter human interpretation. The annotation app collects classification, segmentation, and image captioning training data, and the evaluation app randomizes the availability of CAD tools to facilitate clinical trials on radiologist enhancement. Demonstrations and source code are hosted at (https://candi.nextgenhealthcare.org), and (https://github.com/mbadge/candi), respectively, under GPL-3 license. Supplementary material is available at Bioinformatics online.


Role of endogenous platelet-derived growth factor in arterial smooth muscle cell migration after balloon catheter injury.
The process of intimal thickening after de-endothelializing injury to the rat carotid artery is dependent on the migration of smooth muscle cells from the media. Recent reports have suggested that platelet-derived growth factor may be an important mediator of migration after injury. We have addressed this issue by directly determining smooth muscle cell migration in injured arteries of animals depleted of platelets and after administration of an antibody that blocks platelet-derived growth factor. Because there is a reported association between plasminogen activator synthesis and smooth muscle cell migration, we assayed the activity levels of plasminogen activators after arterial injury and also assessed the effect of a plasmin inhibitor on migration. The data suggest that platelet-derived growth factor, released by platelets at sites of arterial injury, is an endogenous mediator of smooth muscle cell migration; that plasmin generation, catalyzed by tissue-type plasminogen activator, is necessary for migration; and that one way in which platelet-derived growth factor may act is by stimulation of the synthesis of tissue-type plasminogen activator by smooth muscle cells.


Castor oil, bath and/or enema for cervical priming and induction of labour.
Castor oil, a potent cathartic, is derived from the bean of the castor plant. Anecdotal reports, which date back to ancient Egypt have suggested the use of castor oil to stimulate labour. Castor oil has been widely used as a traditional method of initiating labour in midwifery practice. Its role in the initiation of labour is poorly understood and data examining its efficacy within a clinical trial are limited. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. To determine the effects of castor oil or enemas for third trimester cervical ripening or induction of labour in comparison with other methods of cervical ripening or induction of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and bibliographies of relevant papers. Clinical trials comparing castor oil, bath or enemas used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. Three trials, involving 233 women, are included. There was no evidence of differences in caesarean section rates between the two interventions in the two trials reporting this outcome (risk ratio (RR) 2.04, 95% confidence interval (CI) 0.92 to 4.55). There were no data presented on neonatal or maternal mortality or morbidity.There was no evidence of a difference between castor oil and placebo/no treatment for the rate of instrumental delivery, meconium-stained liquor, or Apgar score less than seven at five minutes. The number of participants was too small to detect all but large differences in outcome. All women who ingested castor oil felt nauseous (RR 59.92, 95% CI 8.46 to 424.52). The three trials included in the review contain small numbers of women. All three studies used single doses of castor oil. The results from these studies should be interpreted with caution due to the risk of bias introduced due to poor methodological quality. Further research is needed to attempt to quantify the efficacy of castor oil as an cervical priming and induction agent.


The effect of disc degeneration on anterior shear translation in the lumbar spine.
Many pathologies involving disc degeneration are treated with surgery and spinal implants. It is important to understand how the spine behaves mechanically as a function of disc degeneration. Shear loading is especially relevant in the natural and surgically stabilized lumbar spine. The objective of our study was to determine the effect of disc degeneration on anterior translation of the lumbar spine under shear loading. We tested 30 human cadaveric functional spinal units (L3-4 and L4-5) in anterior shear loading. First, the specimens were imaged in a 1.5 T magnetic resonance scanner. The discs were graded according to the Pfirrmann classification. The specimens were then loaded up to 250 N in anterior shear with an axial compression force of 300 N. Motion of the vertebrae was captured with an optoelectronic camera system. Inter- and intra-observer reliability for disc grading was determined (Cohen's and Fleiss' Kappa), and a non-parametric test was performed on the translation data to characterize the effect of disc degeneration on this parameter. We found fair to moderate agreement between and within observers for the disc grading. We found no significant effect of disc degeneration on anterior shear translation (Kruskal-Wallis ANOVA). Our results indicate that disc degeneration, as classified with the Pfirrmann scale, does not predict lumbar spinal motion in shear.


Impact of pretest on posttest knowledge scores with a Solomon Four research design.
There is a paucity of research on the effects of pretest measurement with prostate cancer screening. What effect does a pretest measurement have on posttest outcomes? This research reports knowledge of prostate cancer screening among men randomized to an Enhanced decision aid versus an Usual Care decision aid. Using a Solomon Four research design, there were a total of 198 men in 4 groups. Most of the sample was African American (78%), with a mean age of 52 years. The greatest posttest knowledge occurred with the Enhanced decision aid in contrast to the Usual Care. The Enhanced/Usual Care groups that had both a pretest and posttest and had received a previous digital rectal examination had the highest means (P = .015), with means of 9.1 and 7.0, respectively. Among men who had a previous digital rectal examination, the greatest increase in score occurred among men randomized to the Enhanced decision aid in contrast to the Usual Care decision aid, 2.9 versus 0.4 (P = .008). The outcome varied based on the status of (1) random group assignment of the Solomon Four design and (2) status of previous digital rectal examination. Implications for nurses include consideration 1 of a pretest to increase posttest knowledge scores.


Physician-assisted suicide: the role of mental health professionals.
A review of the literature was conducted to better understand the (potential) role of mental health professionals in physician-assisted suicide. Numerous studies indicate that depression is one of the most commonly encountered psychiatric illnesses in primary care settings. Yet, depression consistently goes undetected and undiagnosed by nonpsychiatrically trained primary care physicians. Noting the well-studied link between depression and suicide, it is necessary to question giving sole responsibility of assisting patients in making end-of-life treatment decisions to these physicians. Unfortunately, the use of mental health consultation by these physicians is not a common occurrence. Greater involvement of mental health professionals in this emerging and debated area is advocated. Beyond describing mental health professionals' role in the assessment of patient competency or decision making capacity, other areas of potential involvement are described. A discussion of ethical principles relevant to this area follows, along with comments on the training necessary to adequately serve patient needs.


Activity-based selection of HIV-1 reverse transcriptase variants with decreased polymerization fidelity.
HIV-1 reverse transcriptase (HIV-1 RT) copies the RNA genome of HIV-1 into DNA, thereby committing errors at an exceptionally high frequency. Viral offspring evolve rapidly and consequently are capable of evading the immune response as well as antiviral treatment. However, error-prone viral replication could drive HIV close to extinction owing to an intolerable load of deleterious mutations. We applied a genetic selection scheme to identify variants of HIV-1 RT with a further increased error rate to study the relationship between error rate and viral replication. Using this approach, we identified 16 mutator candidates, two of which were purified and further studied in vitro. One of these variant enzymes showed a generally increased mutation frequency as compared with the reference enzyme. A single amino acid residue, R448, is probably responsible for the observed effect. Mutation of this residue, which is located within the RNase H domain of HIV-1 RT, seems to perturb the interaction with template RNA and consequently affects polymerase activity and fidelity.


Management of intracerebral hemorrhage.
Following quickly behind improvements in acute ischemic stroke care have been important advances in the understanding and management of intracerebral hemorrhage (ICH). Among these are accurate diagnosis of cerebral amyloid angiopathy (CAA) during life, recognition of the association between CAA and warfarin-related ICH, use of newer hemostatic treatments, and the combination of minimally invasive surgery with hematoma thrombolysis. Currently recommended management includes prompt evaluation of the patient at a facility with stroke and neurosurgical expertise, consideration of early surgery for patients with clinical deterioration or cerebellar hemorrhages larger than 3 cm, and early treatment of coagulopathies and other neurologic and medical complications. Over the past 2 years, two major randomized studies in ICH (comparing early surgery with best medical management and testing the utility of hemostatic treatment within 4 hours using recombinant factor VIIa) have yielded neutral results. This review focuses on comprehensive management of ICH in light of recent evidence.


Mechanical properties of ProTaper Gold nickel-titanium rotary instruments.
To evaluate and compare the resistance to cyclic fatigue and torsional stress, flexibility and surface microhardness of ProTaper Gold (PTG; Dentsply, Tulsa Dental Specialties, Tulsa, OK, USA) system with ProTaper Universal (PTU; Dentsply Maillefer, Ballaigues, Switzerland). PTG and PTU instruments were rotated in simulated canals and the number of cycles to failure was recorded to assess their cyclic fatigue resistance. Torsional strength was measured using a torsiometer after fixing firmly the apical 3 mm of the instrument. A scanning electron microscope was used to characterize the topographic features of the fracture surfaces of the broken instruments. The instruments were tested for bending resistance using cantilever-bending test. Vickers microhardness was measured on the cross section of instruments with 300 g load and 15 s dwell time. Data were analysed statistically using independent t-tests. Statistical significance was set at P < 0.05. PTG instruments had a significantly higher resistance to cyclic fatigue and flexibility than PTU (P < 0.001). The fractured cross-sectional surfaces revealed typical features of cyclic fractures, including crack origins, fatigue zones and overload fast fracture zones. On the other hand, PTU instruments were associated with higher resistance to torsional stress and microhardness than PTG instruments (P < 0.001). After torsional tests, the fractured cross-sectional surfaces revealed skewed dimples near the centre of the fracture surfaces and circular abrasion streaks. The PTG instrument had improved resistance to cyclic fatigue and flexibility compared with PTU. PTU instruments had improved resistance to torsional stress and microhardness compared with PTG.


The effect of emergency department crowding on analgesia in patients with back pain in two hospitals.
The authors assessed the association between measures of emergency department (ED) crowding and treatment with analgesia and delays to analgesia in ED patients with back pain. This was a retrospective cohort study of nonpregnant patients who presented to two EDs (an academic ED and a community ED in the same health system) from July 1, 2003, to February 28, 2007, with a chief complaint of "back pain." Each patient had four validated crowding measures assigned at triage. Main outcomes were the use of analgesia and delays in time to receiving analgesia. Delays were defined as greater than 1 hour to receive any analgesia from the triage time and from the room placement time. The Cochrane-Armitage test for trend, the Cuzick test for trend, and relative risk (RR) regression were used to test the effects of crowding on outcomes. A total of 5,616 patients with back pain presented to the two EDs over the study period (mean+/-SD age=44+/-17 years, 57% female, 62% black or African American). Of those, 4,425 (79%) received any analgesia while in the ED. A total of 3,589 (81%) experienced a delay greater than 1 hour from triage to analgesia, and 2,985 (67%) experienced a delay more than 1 hour from room placement to analgesia. When hospitals were analyzed separately, a higher proportion of patients experienced delays at the academic site compared with the community site for triage to analgesia (87% vs. 74%) and room to analgesia (71% vs. 63%; both p<0.001). All ED crowding measures were associated with a higher likelihood for delays in both outcomes. At the academic site, patients were more likely to receive analgesia at the highest waiting room numbers. There were no other differences in ED crowding and likelihood of receiving medications in the ED at the two sites. These associations persisted in the adjusted analysis after controlling for potential confounders of analgesia administration. As ED crowding increases, there is a higher likelihood of delays in administration of pain medication in patients with back pain. Analgesia administration was not related to three measures of ED crowding; however, patients were actually more likely to receive analgesics when the waiting room was at peak levels in the academic ED.


Explicit or presumed consent and organ donation post-mortem: does it matter?
In the last 25 years almost every West European country has enacted a transplantation law. During the preparation of these laws an important issue was whether to base the transplantation law on explicit or presumed consent regarding organ donation post-mortem. A common view of supporters of the presumed consent system is that it will result in more organ donors than the rule of explicit consent. In this article the difference between the different systems is further explored. For that purpose, the systems for post mortem donation in 10 West European countries will be discussed. Focus will be on the legal role of relatives within the consent process and finally on the role of relatives in practice. It will be argued that the difference between the two types of systems is less important than it seems to be at first sight.


[Effects of chronic morphine treatment on inositol phosphates contents and PKC activity in mouse brain].
By inducing morphine dependence in mice, changes in inositol phosphate contents, protein kinase C(PKC) activity in brain regions and effect of PKC inhibitor on the development of morphine dependence were investigated. It was found that: (1) IP(inositol phosphate) and IP3 (inositol trisphosphate) contents in striatum, IP in cerebral cortex and total inositol phosphates(IP + IP2 + IP3) in striatum and cerebral cortex were markedly higher than those of the control. But no similar changes in hippocampus and cerebellum were observed. (2) Cytosolic PKC activity was significantly increased in cerebellum and cerebral cortex but decreased in striatum. The membrane PKC activity was apparently enhanced in striatum but decreased in cerebellum and hippocampus. (3) PKC inhibitor was found to prevent the development of morphine dependence. (4) These changes described above were not observed in mice treated with naloxone 30 min prior to daily morphine injection. Our data indicate that the increase of inositol phosphate contents in striatum implied activation of phospholipase C, which might lead to PKC activation. This PKC activation may be involved in the development of morphine dependence.


The treatment of head and neck carcinoma with adriamycin and bleomycin using adjuvant hyperthermia.
Twenty-two cases of carcinoma of the head and neck (predominantly squamous), in a variety of sites, were treated with an oncolytic regime of Adriamycin and Bleomycin. Adjuvant hyperthermia was given to all cases; differing techniques of drug administration were used, depending on whether a case had received previous irradiation. Twenty-one cases showed response to treatment. Post-irradiation cases fared less well than those in which radiotherapy was synchronised with treatment.


Heart rhythm characterization through induced physiological variables.
Atrial fibrillation remains a major cause of morbi-mortality, making mass screening desirable and leading industry to actively develop devices devoted to automatic AF detection. Because there is a tendency toward mobile devices, there is a need for an accurate, rapid method for studying short inter-beat interval time series for real-time automatic medical monitoring. We report a new methodology to efficiently select highly discriminative variables between physiological states, here a normal sinus rhythm or atrial fibrillation. We generate induced variables using the first ten time derivatives of an RR interval time series and formally express a new multivariate metric quantifying their discriminative power to drive state variable selection. When combined with a simple classifier, this new methodology results in 99.9% classification accuracy for 1-min RR interval time series (n = 7,400), with heart rate accelerations and jerks being the most discriminant variables. We show that the RR interval time series can be drastically reduced from 60 s to 3 s, with a classification accuracy of 95.0%. We show that heart rhythm characterization is facilitated by induced variables using time derivatives, which is a generic methodology that is particularly suitable to real-time medical monitoring.


Belief embodiment through eye movements facilitates memory-guided navigation.
Neural network models optimized for task performance often excel at predicting neural activity but do not explain other properties such as the distributed representation across functionally distinct areas. Distributed representations may arise from animals' strategies for resource utilization, however, fixation-based paradigms deprive animals of a vital resource: eye movements. During a naturalistic task in which humans use a joystick to steer and catch flashing fireflies in a virtual environment lacking position cues, subjects physically track the latent task variable with their gaze. We show this strategy to be true also during an inertial version of the task in the absence of optic flow and demonstrate that these task-relevant eye movements reflect an embodiment of the subjects' dynamically evolving internal beliefs about the goal. A neural network model with tuned recurrent connectivity between oculomotor and evidence-integrating frontoparietal circuits accounted for this behavioral strategy. Critically, this model better explained neural data from monkeys' posterior parietal cortex compared to task-optimized models unconstrained by such an oculomotor-based cognitive strategy. These results highlight the importance of unconstrained movement in working memory computations and establish a functional significance of oculomotor signals for evidence-integration and navigation computations via embodied cognition.


Endothelial COX-1 and -2 differentially affect reactivity of MVB in portal hypertensive rats.
Expression of constitutive and inducible cyclooxygenase (COX-1 and COX-2, respectively) and the role of prostanoids were investigated in the aorta and mesenteric vascular bed (MVB) from the portal vein-ligated rat (PVL) as a model of portal hypertension. Functional experiments were carried out in MVB from PVL and sham-operated rats in the absence or presence of the nonselective COX inhibitor indomethacin or the selective inhibitors of COX-1 (SC-560) or COX-2 (NS-398). Western blots of COX-1 and COX-2 proteins were evaluated in aorta and MVB, and PGI(2) production by enzyme immunoassay of 6-keto-PGF(1alpha) was evaluated in the aorta. In the presence of functional endothelium, decreased contraction to norepinephrine (NE) and increased vasodilatation to ACh were observed in MVB from PVL. Exposure of MVB to indomethacin, SC-560, or NS-398 reversed the hyporeactivity to NE and the increased endothelial vasodilatation to ACh in PVL, with NS-398 being more potent than the other two inhibitors. Upregulation of COX-1 and COX-2 expressions was detected in aorta and MVB from PVL portal hypertensive rats, and increased production of 6-keto-PGF(1alpha) was observed in aorta from portal hypertensive rats. These results suggest that generation of endothelial vasodilator prostanoids, from COX-1 and COX-2 isoforms, accounts for the increased mesenteric blood flow in portal hypertension.


[A case of scirrhous stomach cancer with follicular lymphoma of the duodenum].
The patient was a 73-year-old woman with hematemesis, who was brought to our hospital by an ambulance. Emergency upper gastrointestinal endoscopy was performed, and a thickened wall and multiple ulcers were noted in the middle- lower region of the stomach body. The biopsy revealed gastric cancer (por), and the macroscopic depth of invasion was up to the subserosal layer. Multiple white granular protruding lesions were observed in the duodenal bulb and were diagnosed as follicular lymphoma by biopsy. As follicular lymphoma generally takes a long time to progress in many cases, the vital prognosis would be determined by the gastric cancer. Thus, total gastrectomy was performed for gastric cancer. For reconstruction, the double-tract method was used. Duodenal follicular lymphoma was continuously monitored by upper gastrointestinal endoscopy. Here, we describe the case of a patient with a complication of follicular lymphoma arising from duodenal and gastric cancer, which is very rare, and report this case along with a literature review.


Single stage cell seeding of small diameter prosthetic cardiovascular grafts.
Small-diameter prosthetic cardiovascular bypass grafts have high occlusion rates. Thrombogenicity caused by the lack of endothelial cells (ECs) on the luminal surface of the grafts is one of the main reasons for its occlusion. One strategy to improve the clinical performance of cardiovascular prosthetic grafts has been to seed its luminal surface with a monolayer of the patient's own ECs. In this strategy a "two stage" seeding procedure is utilized whereby cells obtained from a vein are amplified in cell culture, then seeded onto a fibrin-arginine-glycine-aspartate (RGD) tripeptide-enriched expanded polytetrafluoroethylene (ePTFE) graft in a rotating bioreactor for one week, after which it is surgically implanted. This achieves patency rates approaching those of vein grafts. The disadvantage of two stage seeding is that it requires culture facilities, a large amount of RGD, which is expensive and is confined to elective cases because of the delay between cell cultivation, seeding, and graft implantation. A single stage seeding using freshly extracted ECs that is transplanted onto the graft at the same time frame of the bypass operation without the need for cell cultivation would be an ideal answer for the disadvantages of two stage seeding. Animal trials have been successful but human trials of single stage seeding have been disappointing. It has been hypothesized that extracted ECs are scarce, furthermore, they are washed off the graft surface once exposed to blood flow. This review examines the various techniques/technologies to improve endothelial cell extraction from various sources and retention onto the luminal surface of prosthetic cardiovascular grafts in order to develop a clinically applicable strategy for single stage seeding.


Pharmacokinetics and therapeutics of acute intramuscular ziprasidone.
Patients with acute psychosis often exhibit agitation, which can be distressing and hazardous to others as well as to the patient. In such psychiatric emergencies, intramuscular antipsychotic agents can be easier to administer than oral formulations, and they have the added advantage of more rapid absorption and a faster onset of action. However, intramuscular formulations of conventional antipsychotics, which have been the standard treatment, are associated with acute dystonia and other movement disorder-related adverse events. Ziprasidone is the first atypical antipsychotic to be clinically available in both intramuscular and oral formulations in the US. The intramuscular formulation of ziprasidone, ziprasidone mesylate, uses sulfobutylether beta-cyclodextrin to solubilise the drug by complexation. The pharmacokinetics of intramuscular ziprasidone include rapid attainment of therapeutic drug level (time to reach peak serum concentration [tmax]<or=60 minutes postdose), a mean terminal elimination half-life ranging from 2 to 5 hours, bioavailability of approximately 100%, exposure to drug that increases in a dose-related manner and little drug accumulation even after 3 days of repeated intramuscular administration. The metabolism and elimination of intramuscular ziprasidone have not been extensively evaluated. The principal difference between any oral versus intramuscular formulations of a drug is in first-pass metabolism. Oral ziprasidone is eliminated mainly via the hepatic route and <1% is eliminated in urine and <4% in faeces as unchanged drug. That would not be expected to change with the intramuscular route of administration. Low concentrations of ziprasidone are seen 12-18 hours after the last intramuscular injection. The rapid clearance of ziprasidone from plasma after an intramuscular administration results in little to no persistence of plasma drug level when switching from intramuscular to oral drug administration. No clinically significant age-, sex- or race-related effects on the pharmacokinetics of intramuscular or oral ziprasidone have been noted, and the tolerability and cardiovascular safety profiles of intramuscular ziprasidone have been well characterised in clinical trials.


[Progress in mechanical circulatory support].
Mechanical circulatory support is an important aspect of the management of patients with severe heart failure. Such support improves survival when treatment with intravenous inotropes or vasodilators, intra-aortic balloon counterpulsation and mechanical ventilation has failed. Technological advances in ventricular assist devices have reduced the risk of postoperative complications. However, risk stratification prior to device implantation is essential for reducing complications over both the short and long term. As knowledge about cardiovascular disease and the range of mechanical devices available continue to develop, the challenge for clinicians will be to use clinical findings to select the device that is most likely to benefit the individual patient. This article describes the circulatory support devices currently available for use in patients, the indications for their use, their beneficial effects on ventricular function, and the advantages and disadvantages of each particular device.


Long-term outcome and factors influencing the outcome of thymectomy for myasthenia gravis.
Thymectomy has gained widespread acceptance as a treatment for patients with myasthenia gravis (MG). Patients with myasthenia gravis who had undergone thymectomy by extended transsternal approach between 1981 and 1987 were retrospectively reviewed to evaluate the result of thymectomy, time to remission, time to maximum improvement and factors influencing remission after thymectomy. There were 128 patients, 45 men and 83 women and the mean ages at the time of thymectomy were 35.7 and 32.2 years respectively. After thymectomy, 41.2% of the patients were in remission, 53% improved and 5.8% had no response. The remission rates at 1, 2, 5 and 10 years after thymectomy were 9%, 17%, 37% and 53% respectively and the median time to remission was 9 years. The maximum improvement rates at 1, 2, 5 and 10 years after thymectomy were estimated to be 30%, 40%, 57% and 78% respectively and the median time to maximum improvement was 3.6 years. Patients with ocular MG, longer duration of symptoms before thymectomy and atrophic thymus gland appeared to take longer to achieve remission although none of the factors was significantly associated with the time to remission. Thymectomy is beneficialfor MG patients with satisfactory remission and improvement rates. It is recommended that thymectomy should be advocatedfor these patients early in the course of the disease because the duration of the symptoms appeared to be the main determinant of the outcome.


Identification of a Pyroptosis-Related Gene Signature and Effect of Silencing the CHMP4C and CASP4 in Pancreatic Adenocarcinoma.
Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with an extremely poor prognosis. Pyroptosis has been demonstrated to play an important role in tumor prognosis. However, the expression of pyroptosis-related genes in PAAD and their correlations with prognosis remains unclear. In this study, the 36 pyroptosis-related genes that were differentially expressed between normal pancreatic tissues and PAAD tissues were identified via the "limma" R package. Based on these differentially expressed genes (DEGs), a five-gene signature was established by applying the least absolute shrinkage and selection operator Cox regression in the TCGA cohort and was validated in the GEO cohort. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of DEGs based on the risk model indicated that immune-associated biological processes and pathways were enriched. In vivo, we detected the expressions of CASP4 and CHMP4C by immunohistochemistry in tumor tissues and adjacent normal tissues. In vitro, we silenced CASP4 and CHMP4C to explore their effects on pancreatic cancer cells. PAAD patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group. The expressions of CASP4 and CHMP4C in tumor tissue were higher than those in the adjacent normal tissues in vivo. The knockdown of CASP4 significantly inhibited the invasion and migration but not the proliferation of PANC-1 cells. The knockdown of CHMP4C obviously inhibited the proliferation, migration, and invasion of PANC-1 cells. Pyroptosis-related genes play important roles in predicting the prognosis of PAAD, and CASP4 and CHMP4C affect the metastasis of PAAD.


Human thyroid adenyl cyclase-stimulating activity in immunoglobulin G of patients with Graves' disease.
We have studied the characteristics of the stimulation of adenyl cyclase (AC) activity in human thyroid plasma membranes by thyroid-stimulating hormone (TSH) and by immunoglobulin G (IgG) from the sera of patients with Graves' disease. AC activity was measured as adenosine 3',5'-cyclic monophosphate (cAMP) generated by membranes in a 10 minute incubation. IgG from two patients with Graves' disease possessed particularly potent human thyroid AC-stimulating activity; the dose-response curves with these IgGs were essentially parallel to those obtained with TSH. As little as 30 mug of the IgG of one patient with Graves' disease or 8 muU of TSH caused significant AC stimulation. A Lineweaver-Burk plot of the data suggested similarity in the site of action of both TSH and human thyroid adenyl cyclase stimulator (HTACS) in Graves' IgG. Submaximal doses of HTACS and TSH had additive effects on AC stimulation, but a large dose of a Graves' IgG with potent AC stimulating activity did not enhance AC stimulation by a maximal dose of TSH. The effect of HTACS on AC was slower in onset and longer in duration than an equipotent dose of TSH. HTACS was detectable in IgGs of 9 of 15 untreated hyperthyroid Graves' disease patients; its concentration, however, did not correlate significantly with tests of thyroid function, nor with long-acting thyroid stimulator (LATS) activity. In another 11 treated patients with Graves' disease, selected for the presence of LATS, HTACS and LATS were significantly correlated. We observed no inhibition of LATS activity in a Graves' IgG chosen for such testing because of its high titer of HTACS and no detectable LATS. However, an inhibitor of HTACS was detected in 2 of 4 IgGs; one of these two IgGs also inhibited AC stimulation by TSH. 1) Some Graves' disease IgGs contain a human thyroid AC stimulator (HTACS), probably different from LATS. 2) HTACS may act via a common pathway with TSH; it differs from TSH, however, in having a slower onset and a greater effect during more prolonged incubation with plasma membranes. 3) There is also an inhibitor of HTACS activity in some Graves' disease IgGs.


Self-Powered Gesture Recognition Wristband Enabled by Machine Learning for Full Keyboard and Multicommand Input.
Virtual reality is a brand-new technology that can be applied extensively. To realize virtual reality, certain types of human-computer interaction equipment are necessary. Existing virtual reality technologies often rely on cameras, data gloves, game pads, and other equipment. These equipment are either bulky, inconvenient to carry and use, or expensive to popularize. Therefore, the development of a convenient and low-cost high-precision human-computer interaction device can contribute positively to the development of virtual reality technology. In this study, a gesture recognition wristband that can realize a full keyboard and multicommand input is developed. The wristband is convenient to wear, low in cost, and does not affect other daily operations of the hand. This wristband is based on physiological anatomy as well as aided by active sensor and machine learning technology; it can achieve a maximum accuracy of 92.6% in recognizing 26 letters. This wristband offers broad application prospects in the fields of gesture command recognition, assistive devices for the disabled, and wearable electronics.


IRSp53 senses negative membrane curvature and phase separates along membrane tubules.
BAR domain proteins contribute to membrane deformation in diverse cellular processes. The inverted-BAR (I-BAR) protein IRSp53, for instance, is found on the inner leaflet of the tubular membrane of filopodia; however its role in the formation of these structures is incompletely understood. Here we develop an original assay in which proteins are encapsulated in giant unilamellar vesicles connected to membrane nanotubes. Our results demonstrate that I-BAR dimers sense negative membrane curvature. Experiment and theory reveal that the I-BAR displays a non-monotonic sorting with curvature, and expands the tube at high imposed tension while constricting it at low tension. Strikingly, at low protein density and tension, protein-rich domains appear along the tube. This peculiar behaviour is due to the shallow intrinsic curvature of I-BAR dimers. It allows constriction of weakly curved membranes coupled to local protein enrichment at biologically relevant conditions. This might explain how IRSp53 contributes in vivo to the initiation of filopodia.


Neutron-encoded mass signatures for multiplexed proteome quantification.
We describe a protein quantification method called neutron encoding that exploits the subtle mass differences caused by nuclear binding energy variation in stable isotopes. These mass differences are synthetically encoded into amino acids and incorporated into yeast and mouse proteins via metabolic labeling. Mass spectrometry analysis with high mass resolution (>200,000) reveals the isotopologue-embedded peptide signals, permitting quantification. Neutron encoding will enable highly multiplexed proteome analysis with excellent dynamic range and accuracy.


Protective effect of juglone on electric field-induced apoptosis and inflammation in liver and kidney tissue in rats.
Electric field (EF) has been shown to cause tissue damage mainly through oxidative stress, inflammation, and apoptosis. Thus, juglone (5-hydroxy-1,4-naphthoquinone) (JUG), which has antioxidant and antiapoptotic properties, is thought to be effective against electric field-induced damage. We aimed to investigate whether 50 Hz alternating current (AC) triggers inflammation and apoptosis in rat liver and kidney tissues and evaluate the JUG supplement's estimated protective effect. Twenty-four adult male wistar albino rats were divided into control, EF and EF + JUG groups, each containing eight rats. The EF and EF + JUG groups were exposed to EF while no EF exposure and JUG were applied to the control group. At the end of the experiment, liver and kidney tissues were collected for histological (H&E, caspase-3 and TNF-α for immunohistochemical staining), and genetics (SOCS, caspase-3 and TNF-α, PCR analyses). After routine histological procedures, sections stained with H&E showed significant changes in liver and kidney tissues in the EF group compared to the control group (p < 0.05). Significant protective effects were observed in the building volumes and histopathology in the EF + JUG group (p < 0.05). Our gene expression results increased the expression of caspase-3 and TNF-α in the EF group (p < 0.001). Juglone increased SOCS expression (p < 0.001). These findings were consistent with the anti-apoptotic and anti-inflammatory effects of JUG treatment. We reasoned that exposure to EF damaged rat liver and kidney tissues and administration of JUG alleviated the complications caused by 50 Hz EF.


[Effects of zibu piyin recipe on the insulin resistance in the hippocampus of pi-yin deficiency diabetic rats].
To study the protection of Zibu Piyin Recipe (ZBPYR) on the insulin signal pathway in the hippocampus of Pi-yin deficiency diabetic encephalopathy rats and to explore its possible mechanisms. The type 2 diabetic model was established using high fat diet and intraperitoneal injection of small dose streptozotocin (STZ). The Pi-yin deficiency model was established referring to classic compound factors. The learning and memory capabilities were tested in rats by the behavioral changes. The protein expressions of hippocampal IRE1alpha, JNK, and IRS-1 were detected using Western blot. There was statistical difference in the learning and memory capabilities of Pi-yin deficiency rats when compared with the blank control group (P<0.05). The learning and memory capabilities could be improved by ZBPYR. The protein expressions of hippocampal phospho-IRS-1, phospho-JNK, and total IRE1alpha were enhanced (P<0.05). But they were weakened after treatment of ZBPYR. ZBPYR could significantly improve the learning and memory capabilities of Pi-yin deficiency diabetic rats. Its functions might be correlated with improving the endoplasmic reticulum stress to regulate the insulin signaling pathway.


Clinical acupuncture therapy for chronic cholecystitis: A protocol for systematic review and meta-analysis.
Chronic cholecystitis is a common chronic disease in clinical practice. The incidence of chronic cholecystitis is gradually increasing due to changes in eating habits and even if acute infections aren't treated in time, it can cause serious complications, continue to plague people's daily life and become an economic burden to society. Currently, the curative effect of chronic cholecystitis under the control of western medicine is still lacking and there are adverse reactions. However, based on current clinical controlled trials acupuncture therapy for chronic cholecystitis has gradually become a complementary treatment. Therefore, this systematic review aims to explore the safety and feasibility of acupuncture therapy in the treatment of chronic cholecystitis. We will search the following databases: Medline, PubMed, Cochrane Database of Systematic Reviews, Embase, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, Wang Fang Database, Chinese Scientific Journal Database from inception to February 2021 without any language restriction. At the same time, relevant literature will be searched manually. The main search terms include: "Acupuncture," "Cholecystitis." Data entry will be completed by 2 researchers separately. After entry, cross-checking will be performed to ensure the authenticity of the information. The main outcome criteria include: including the total effective rate of the patient; the traditional Chinese medicine symptom score of the patient includes: abdominal pain, tenderness in the right upper abdomen, and so on; secondary outcome criteria include: gallbladder contraction function and gallbladder thickness, VAS scores, recurrence rate, adverse reactions; use Cochrane risk bias assessment to evaluate and score the included randomized controlled trial; meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test is based on the thresholds of P and I2, In order to use solid or random effects models. This systematic review only evaluates the safety and limitations of acupuncture therapy in the treatment of chronic cholecystitis. We will report the full text in the near future. This study will explore the safety and limitations of acupuncture therapy in the treatment of chronic cholecystitis, so that acupuncture therapy will be more widely used clinically. INPLASY202120020.


Worker and manager perceptions of the utility of work-related mental health literacy programmes delivered by community organisations: a qualitative study based on the theory of planned behaviour.
Reluctance to seek help is a leading contributor to escalating mental injury rates in Australian workplaces. We explored the benefit of using community organisations to deliver mental health literacy programmes to overcome workplace barriers to help-seeking behaviours. This study used a qualitative application of the theory of planned behaviour to examine underlying beliefs that may influence worker's intentions to participate in mental health literacy programmes delivered by community organisations and manager support for them. This study took place within three large white-collar organisations in the Australian state of Victoria. Eighteen workers and 11 managers (n=29) were interviewed to explore perspectives of the benefits of such an approach. Community organisations have six attributes that make them suitable as an alternative mental health literacy programme provider including empathy, safety, relatability, trustworthiness, social support and inclusivity. Behavioural beliefs included accessibility, understanding and objectivity. The lack of suitability and legitimacy due to poor governance and leadership was disadvantages. Normative beliefs were that family and friends would most likely approve, while line managers and colleagues were viewed as most likely to disapprove. Control beliefs indicated that endorsements from relevant bodies were facilitators of participation. Distance/time constraints and the lack of skills, training and lived experiences of coordinators/facilitators were seen as barriers. Identifying workers' beliefs and perceptions of community organisations has significant implication for the development of effective community-based strategies to improve worker mental health literacy and help seeking. Organisations with formal governance structures, allied with government, peak bodies and work-related mental health organisations would be most suitable. Approaches should focus on lived experience and be delivered by qualified facilitators. Promoting supervisor and colleague support could improve participation. Models to guide cross-sector collaborations to equip community organisations to deliver work-related mental health literacy programmes need to be explored.


Visually evoked eye movements in mouse mutants and inbred strains. A screening report.
The authors screened various inbred strains and mutants of the mouse, Mus musculus, for qualitatively abnormal or reduced numbers of optokinetic nystagmus (OKN) eye movements. Thirteen hypopigmentation mutants and ten neuromuscular mutants were found to have abnormal or markedly reduced OKN, but none of these mutants had retinal degeneration. Ten other hypopigmentation mutants and nine other neuromuscular mutants had relatively normal OKN, thus showing that neither hypopigmentation nor neuromuscular abnormality per se are well-correlated with abnormal OKN. These findings show that many mutants with visual defects are available from existing holdings. These visual mutants may serve as a resource for the study of the function and development of the mammalian visual system.


Biomarkers in the clinical diagnosis and management of traumatic brain injury.
Traumatic brain injury (TBI) is the leading cause of death and disability among young adults. Numerous safety improvements in the workplace, the addition of airbags to vehicles, and the enforcement of speed limits have all helped to reduce the incidence and severity of head trauma. While improvements in emergency response times and acute care have increased TBI survivability, this has heightened the necessity for developing reliable methods to identify patients at risk of developing secondary pathologies. At present, the primary clinical indicators for the presence of brain injury are the Glasgow Coma Scale (GCS), pupil reactivity, and head computed tomography (CT). While these indices have proven useful for stratifying the magnitude and extent of brain damage, they have limited utility for predicting adverse secondary events or detecting subtle damage. Biomarkers, reflecting a biological response to injury or disease, have proven useful for the diagnosis of many pathological conditions including cancer, heart failure, infection, and genetic disorders. For TBI, several proteins synthesized in astroglial cells or neurons have been proposed as potential biomarkers. These proteins include the BB isozyme of creatine kinase (CK-BB, predominant in brain), glial fibrilary acidic protein (GFAP), myelin basic protein (MBP), neuron-specific enolase (NSE), and S100B.The presence of these biomarkers in the cerebrospinal fluid and serum of patients with moderate-to-severe TBI, and their correlation with outcome, suggest that they may have utility as surrogate markers in clinical trials. In addition, many of these markers have been found to be sensitive indicators of injury, and therefore may have the potential to diagnose persons with mild TBI. In addition to biomarkers that correlate with long-term outcome, a few studies have identified prognostic biomarkers for secondary injury that may be useful in individualizing patient management.


Functional expression of murine multidrug resistance in Xenopus laevis oocytes.
The development of multidrug resistance (MDR) is associated with the overproduction of a plasma membrane glycoprotein, P glycoprotein. Here we report the functional expression of a member of the murine mdr family of proteins and show that Xenopus oocytes injected with RNA encoding the mouse mdr1b P glycoprotein develop a MDR-like phenotype. Immunological analysis indicated that oocytes injected with the mdr1b RNA synthesized a protein with the size and immunological characteristics of the mouse mdr1b P glycoprotein. These oocytes exhibited a decreased accumulation of [3H]vinblastine and showed an increased capacity to extrude the drug compared to control oocytes not expressing the P glycoprotein. In addition, competition experiments indicated that verapamil, vincristine, daunomycin, and quinidine, but not colchicine, can overcome the rapid drug efflux conferred by the expression of the mouse P glycoprotein.


Late diagnosis in congenital dislocation of the hip.
In 1966-1975, congenital dislocation of the hip was diagnosed after the neonatal period in 115 children in Uusimaa county in southern Finland; the incidence was 0.76 per thousand liveborns. No decreasing tendency could be seen during the time of the investigation. In most children, the diagnosis was made during the first medical examination at the child welfare clinic at the average age of 3 months. The number of children diagnosed at walking age seemed to be decreasing. The numbers of boys and bilateral affections were smaller in this group than among cases diagnosed during the neonatal period. Dislocation was suspected in 23 per cent of the children even before the diagnosis was made. The reasons for the delay are given and discussed. In 1981, 66 per cent of the children were symptomless and no radiographic signs could be seen. Sixteen per cent of the children had minor residual signs with no need for follow-up, and in 18 per cent the outcome was still unclear.


A patient's perspective of chronic pain.
Sara Gilbert Nadler speaks to Jade Parker, Commissioning Editor: Sara has obtained a Bachelor's Degree and Master's in social work. Her field of practice in social work has been in the field of medical social work. Sara has worked in the field of medical social work for over 20 years; her work has spanned from acute care hospitals to skilled nursing facilities. Her professional responsibilities include case management, discharge planning, financial management, counselling patients and their families in regard to their medical conditions as well as making referrals to home care agencies and other care providers if necessary. At present she is a volunteer at Community Health Advocates, New York. She works on the telephone help line, handles health insurance issues along with answering questions in regard to the affordable care act. She also advocates if a client is having issues with their health insurance company in terms of coverage issues. She works with the client and their insurance company and any other agency that needs to advocate on their behalf.


Physio-mitotic theory and a new concept of leukemia development.
In the physio-mitotic theory described previously by the authors (10), general mitosis consists of two different types: essential duplication and converted maturation. These two types of mitosis are regulated by mechanisms involving maturation and duplication factors, and each plays a role in the antagonistic histological development of the other.According to this theory, every kind of leukocyte is produced through mitosis in the bone marrow and migrates during cell turnover to the bloodstream. However, in leukemia a highly excessive number of leukocytes and leuko-blastocysts appear in the bloodstream. This excessive amount is greater than the physiological capability of cells in the bone marrow alone. Such an extremely large group of cells would not be produced without being dependent on an extremely high ratio of produced leukocytes to original stem cells. This extremely high ratio may be due to a systematic pathological deterioration of the mitotic maturation ability during the maturation process of the leuko-blastocysts. Consequently, restoration of the deterioration to the original mitotic maturation response of the normal leuko-blastocysts may be an essential event in achieving leukemia eradication, rather than persistent destruction of individual leukemic leukocytes.


How Competitive are Integrated Vascular Surgery Residency Programs? A Ten-Year Comparison Using a Normalized Competitive Index.
Integrated vascular surgery residency (VS) programs have increased in popularity and offer an accelerated track compared to the traditional fellowship pathway. We sought to create a simple metric for medical students to better assess the competitiveness of VS training programs compared to general surgery (GS) programs. GS and VS programs were compared using the National Resident Matching Program match data from 2012 to 2021. Applicant metrics (board scores, research output and experiences, work experiences, and volunteer experiences) from 2015 to 2019 were obtained using the Association of American Medical Colleges Report on Residents. A competitive index (CI) was created (number of programs ranked per applicant divided by match rate) for each specialty and normalized (NCI) to a value of 1 to improve longitudinal comparisons. NCI and number of programs ranked per applicant were plotted across time and a linear regression was performed to evaluate a 10-year trend. The match rate of both specialties was 52% and was similar for GS and VS programs. CI was higher for VS compared to GS (18.4 ± 3.0 vs. 14.5 ± 0.4; P < 0.001). The number of programs ranked per applicant was higher in VS compared to GS (9.4 vs. 7.7, P < 0.05). The linear regression revealed increasing NCI and number of programs ranked per applicant over time for VS programs compared to GS with all R2 > 0.61 (P < 0.001). Matching into a VS programs is becoming increasingly competitive. The average CI was approximately 27% higher for VS programs compared to GS programs despite similar match rates. As VS programs continue to evolve, NCI may be a more useful metric for applicants.


Surface Inoculation and Quantification of Pseudomonas syringae Population in the Arabidopsis Leaf Apoplast.
Bacterial pathogens must enter the plant tissue in order to cause a successful infection. Foliar bacterial pathogens that are not able to directly penetrate the plant epidermis rely on wounds or natural openings to internalize leaves. This protocol describes a procedure to estimate the population size of Pseudomonas syringae in the leaf apoplast after surface inoculation of Arabidopsis rosettes.


Could autonomic nervous system parameters be still helpful in identifying patients with left ventricular systolic dysfunction at the highest risk of all-cause mortality?
Autonomic imbalance is associated with poor prognosis of patients with systolic dysfunction. Most of the previous data were written several years ago and constituted to cardiovascular or arrhythmic mortality. The current treatment of these patients has improved substantially over the last decades, and thus, the population at risk of death may have altered as well. Consequently, data on high-risk patients with systolic dysfunction in the modern era are sparse and those from previous trials may no longer be applicable. The aim herein, was to verify whether well-known autonomic indices - baroreflex sensitivity (BRS) and heart rate variability (HRV) - remain accurate predictors of mortality in patients with systolic dysfunction. Non-invasively obtained BRS and HRV were analyzed in 205 clinically stable patients with left ventricular ejection fraction (LVEF) ≤ 40%. 28 patients died within 28 ± 9 month follow-up. Baroreflex sensitivity, low-frequency (LF) in normalized units, LF to high-frequency ratio and standard deviation of average R-R intervals were significantly associated with mortality; cut-off values of the highest discriminatory power for abovementioned parameters were ≤ 3.0 ms/mmHg, ≤ 41, ≤ 0.7 and ≤ 25 ms, respectively. In bivariate Cox analyses (adjusted for LVEF, New York Heart Association [NYHA] or absence of implantable cardioverter-defibrillator [ICD]) autonomic indices remain significant predictors of death. Baroreflex sensitivity and HRV - may still be helpful in identifying patients with left ventricular systolic dysfunction at the highest risk of all-cause mortality, independently of LVEF, NYHA class, and ICD implantation.


Communicating the Neuroscience of Psychopathy and Its Influence on Moral Behavior: Protocol of Two Experimental Studies.
Neuroscience has identified brain structures and functions that correlate with psychopathic tendencies. Since psychopathic traits can be traced back to physical neural attributes, it has been argued that psychopaths are not truly responsible for their actions and therefore should not be blamed for their psychopathic behaviors. This experimental research aims to evaluate what effect communicating this theory of psychopathy has on the moral behavior of lay people. If psychopathy is blamed on the brain, people may feel less morally responsible for their own psychopathic tendencies and therefore may be more likely to display those tendencies. An online study will provide participants with false feedback about their psychopathic traits supposedly based on their digital footprint (i.e., Facebook likes), thus classifying them as having either above-average or below-average psychopathic traits and describing psychopathy in cognitive or neurobiological terms. This particular study will assess the extent to which lay people are influenced by feedback regarding their psychopathic traits, and how this might affect their moral behavior in online tasks. Public recognition of these potential negative consequences of neuroscience communication will also be assessed. A field study using the lost letter technique will be conducted to examine lay people's endorsement of neurobiological, as compared to cognitive, explanations of criminal behavior. This field and online experimental research could inform the future communication of neuroscience to the public in a way that is sensitive to the potential negative consequences of communicating such science. In particular, this research may have implications for the future means by which neurobiological predictors of offending can be safely communicated to offenders.


Getting your message through to your hard of hearing or deaf patients or families.
Of the more than 28 million people in the United States who are deaf or hard of hearing, about 40% of this population is found in the elderly. The information in this article will help plastic surgical nurses understand the Deaf culture better as well as provide inventory of communication possibilities so your dialogue is both complete and effective. The following simple guidelines can help make communication between you and your deaf patient more effective.


Stereoelectronic tuning of the structure and stability of the trp cage miniprotein.
Proline residues are critical structural elements in proteins, defining turns, loops, secondary structure boundaries, and polyproline helices. Control of proline conformation therefore may be used to define protein structure and stability. 4-Substituted proline derivatives may be used to control proline ring pucker, which correlates with protein main chain conformation. To examine the use of proline conformational restriction to tune globular protein stability, a series of peptides derived from the trp cage miniprotein was synthesized. Proline at residue 12 of the trp cage miniprotein, which adopts a Cgamma-exo ring pucker in the NMR structure, was replaced with 4-substituted proline derivatives, including 4R derivatives favoring a Cgamma-exo ring pucker and 4S derivatives favoring a Cgamma-endo ring pucker. Eight trp cage peptides were synthesized, five of which included residues that are not commercially available, without requiring any solution phase chemistry. Analysis of the trp cage peptides by circular dichroism and NMR indicated that the structure and stability of the trp cage miniprotein was controllable based on the conformational bias of the proline derivative. Replacement of Pro12 with 4S-substituted proline derivatives that favor the Cgamma-endo ring pucker destabilized the trp cage, while replacement of Pro12 with 4R-substituted proline derivatives that favor a Cgamma-exo ring pucker resulted in increased alpha-helicity and thermal stability of the trp cage. The most stable trp cage derivatives contained benzoates of 4R-hydroxyproline, which also exhibited the most pronounced stereoelectronic effects in TYProxN model peptides. Overall, the stability of the trp cage was tunable by over 50 degrees C depending on the identity of the proline side chain at residue 12.


Management of stroke and transient ischemic attack.
Stroke is a major cause of death and disability. The resulting burden on society continues to grow, despite recent advances in acute stroke therapy. Thrombolysis reduces stroke morbidity but is only applicable to a small percentage of stroke patients. Acute stroke units, which allow for the greatest overall improvement in outcome, provide the best facilities for acute intervention. Despite recent advances in acute management, such as endarterectomy and anticoagulation, primary and secondary preventive measures to control stroke risk factors, along with appropriate specific interventions, are the key to reducing the overall burden of stroke.


Different pitch configurations constrain the external and internal loads of young professional soccer players during transition games.
The aims of this study were to compare the influence of transition game (TG) size on the external and internal loads of young professional soccer players and to describe the high-speed profile of these drills in response to pitch dimensions. Eighteen young professional soccer players (age: 16.1 ± 0.3 years; height: 178.3 ± 5.4 cm; weight: 70.1 ± 6.2 kg) performed a 3vs2 TG on pitches measuring 40 × 30 m (TG30), 40 × 50 m (TG50) and 40 × 70 m (TG70) m. Distance covered (DC); accelerations-decelerations above 1.0 m · s-2 and 2.5 m · s-2; rate of perceived exertion (RPE); maximal heart rate and time above 90%; DC at 18.0 to 21.0 km · h-1 (DC 18-20.9 km · h-1); DC at 21.0 to 23.9 km · h-1 (DC 21-23.9 km · h-1); DC above 24.0 km · h-1 (DC > 24 km · h-1); and peak speed and sprint profile (duration, distance and maximal speed) were measured. TG30 achieved lower DC, DC above 18 km · h-1, peak speed, sprint distance and RPE than TG50 and TG70 (p < 0.01 and p < 0.05) and lower sprint duration and maximal speed sprint than TG70 (p < 0.01). TG30 and TG50 achieved higher Acc > 1.0 and > 2.5 m · s-2 respectively than TG70 (p < 0.05). TG70 showed greater DC above 21 km · h-1, peak speed, sprint distance and maximal speed sprint than TG50 (p < 0.01). Soccer coaches should use larger TGs to overload variables related to high speed and sprint demands during training and smaller TG formats to stimulate the accelerations of the soccer players.


The 2A proteinase of human rhinovirus is a zinc containing enzyme.
The 2A proteinase of human rhinovirus (HRV) 2 is a cysteine proteinase which is not inhibited by metal chelating agents. However, total hydrolysis of highly purified HRV2 2A followed by atom emission spectroscopy demonstrated that HRV2 2A contains 1 mol of zinc per mole of enzyme. Furthermore, Zn depletion of the enzyme led to a loss of proteolytic activity which could subsequently be restored by Zn supplementation.


Microdetermination of serum calcium by parallel fast analyzer.
An adaptation of a direct microdetermination of serum calcium based upon its colored reaction product with cresolphthalein complexone for use with a parallel fast analyzer is described. It is simple, reliable and clinically accurate. Twenty microliters of sample are employed in a final volume of 650 mul. Comparison studies with an atomic absorption method resulted in a correlation coefficinet (r) of 0.94. Replicate analyses at normal (8.5 mg. per dl.) and abnormal (12.1 mg. per dl) levels showed inter-day coefficients of variation of 3.2 and 2.3%, respectively. Assays of sera of male and female donors (age range: 17--60 years) showed normal ranges of 8.5--10.8 and 8.5--10.5 mg. per dl., respectively. Moderate hemolysis and jaundice and mild lipemia are associated with spuriously high results. Magnesium in serum showed no significant effect below 4.0 mEq. per l.


Current contraceptive status among women aged 15-44: United States, 2011-2013.
Nearly all women use contraception at some point in their lifetimes, although at any given time they may not be using contraception for reasons such as seeking pregnancy, being pregnant, or not being sexually active. Using data from the 2011-2013 National Survey of Family Growth (NSFG) on contraceptive use in the month of the interview, this report provides a snapshot of current contraceptive status among women aged 15-44 in the United States. In addition to describing use of any method by age, Hispanic origin and race, and educational attainment, patterns of use are described for the four most commonly used contraceptive methods: the oral contraceptive pill, female sterilization, the male condom, and long-acting reversible contraceptives, which include contraceptive implants and intrauterine devices.