Percutaneous screw fixation assisted by hollow pedicle finder for superior pubic ramus fractures.
Pubic ramus fracture was an injury of anterior pelvic ring, the anterior pelvic ring plays an important role in maintaining the stability of the pelvis. The purpose of this study was to investigate the effect and indication of percutaneous retrograde pubic screw fixation assisted by hollow pedicle finder for pubic ramus fractures. The clinical data of 68 patients with pubic ramus fracture treated with cannulated screw from March 2008 to March 2020 were retrospectively analyzed. According to the surgical methods, they were divided into traditional surgery group (32 cases in group A, with traditional retrograde pubic screw fixation) and modified surgery group (36 cases in group B, with percutaneous retrograde pubic screw fixation assisted by hollow open circuit device). Operation time, blood loss, incision length, screw length and complications were recorded and compared between the two groups. On the second day after surgery, the maximum fracture displacement over plain radiographs, entrance radiographs and exit radiographs of the pelvis was evaluated according to Matta criteria to evaluate the postoperative fracture reduction. Majeed score was used to evaluate the hip function at 12 months after surgery. The operations were successfully completed in both groups. The operation time, blood loss and incision length in group B were significantly less than those in group A (P < 0.05). There was no significant difference in screw length between the two groups (t = 0.797, P = 0.431). All patients were followed up for 8-38 months (mean 21.8 months). There were no vascular and nerve injury, fracture of internal fixator, screw entry into joint cavity, fracture nonunion and other complications in both groups. The fracture healing time of the two groups was 23.1 ± 2.1 weeks in group A while 22.7 ± 2.1 weeks in group B, respectively, and there was no statistical difference in the fracture healing time between the two groups (P > 0.05). In group A, there were 3 cases of incision infection, 1 case of incision fat liquefaction and 2 cases of lower extremity deep venous thrombosis, and the complication rate was 18.8%. There was only 1 case of lower extremity deep vein thrombosis in group B, and the complication rate was 2.8%, which was significantly lower than that in group A. The fracture in one case after surgery was found to be displaced in group A and no fracture was found in group B. There was no significant difference between the two groups in Matta imaging evaluation on the next day after surgery and Majeed function evaluation at 12 months after surgery (P > 0.05). Percutaneous retrograde pubic ramus screw fixation assisted by hollow pedicle finder is effective in the treatment of pelvic pubic ramus fracture. It has the advantages of less incision, shorter operation time, less blood loss and lower incidence of complications compared with traditional methods. However, correct surgical indications should be required when we apply this surgical method.


Detection of HCV and HIV-1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing.
To reduce the risk of transfusion-transmissible viruses entering the blood supply, the nucleic acid amplification testing (NAT) was implemented to screen Scottish and Northern Irish blood donations in minipools. After 5 years of NAT for hepatitis C virus (HCV) and 2 years for human immunodeficiency virus-1 (HIV-1), the yield of serologically negative, nucleic acid positive 'window donations' and cost-benefit of NAT is under review. When the Scottish National Blood Transfusion Service (SNBTS) implemented NAT in 1999, a fully automated 'black box' system was not available. Therefore, an 'in-house' assimilated NAT assay was developed, validated and implemented. The system is flexible and allows testing for additional viral markers to be introduced with relative ease. The HCV and HIV NAT assays have 95% detection levels of 7.25 IU/ml and 39.8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1.9 million) and one HIV (1 in 0.77 million) window donation have been detected in 5 and 2 years, respectively, of NAT. The SNBTS NAT assays are robust and have performed consistently over the last 5 years. The design of the in-house system allowed HIV NAT to be added in 2003 at a relatively small additional cost per sample, although for both assays, the royalty fee far exceeds the cost of the test itself. Clearly NAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAT. SUMMARY SENTENCE: The yield of HCV and HIV NAT in UK is significantly less than that anticipated from statistical models.


Modulation of MPP+ uptake by tea and some of its components in Caco-2 cells.
The entry of most xeno/endobiotics into the organism is limited by their intestinal absorption. The interference of certain foods with the therapeutic efficacy of drugs or with chemical toxicity is becoming evident and growing attention is being given to these subjects. The aim of this work was to study the effect of green tea (GT) and black tea (BT), as well as some of their components, on the transport of organic cation molecules. For this purpose, 3H-MPP+ (radiolabeled 1-methyl-4-phenylpyridinium) was used as a model organic cation and Caco-2 cells were used as an intestinal epithelial model. Our results showed that both GT and BT significantly increased 3H-MPP+ absorption in these cells. Additionally, we studied the effect of epigallocatechin-3-gallate (EGCG), myricetin, caffeine, and theophylline. Whereas EGCG (2 mM) increased, myricetin (50 microM) and caffeine (1 mM) decreased, and theophylline (1 mM) had no effect on the uptake of 3H-MPP+ into Caco-2 cells. When GT was supplemented with caffeine or theophylline, we observed a partial loss of its effect. When BT was supplemented with EGCG, its ability to increase 3H-MPP+ uptake was much more pronounced than that observed with BT alone. In conclusion, this study showed that GT and BT might interfere with the absorption of the model organic cation MPP+ by the intestinal epithelium. Since important compounds are organic cations, the consequences of this interference may have an impact on human health. Although this constitutes only preliminary work and further studies are needed, tea should be included in the growing list of foodstuffs that have the potential to be involved in food-drug interactions.


Comparative responses of Achillea millefolium ecotypes to competition and soil type.
Achillea millefolium populations from adjacent sites with zonal and serpentime soil were used to test predictions about the relation between growth and the competitive ability of plants in productive and unproductive environments. Under greenhouse conditions, individually-grown plants from both sources grew larger in serpentine soil than in zonal soil; serpentine plants accumulated 72% more biomass than zonal plants. In zonal soil, zonal plants were 71% larger than serpentine plants, although these differences were not statistically significant, and plants from both sources accumulated much less biomass and were shorter than plants growing in serpentine soil. In a high density, fertilized replacement series, zonal plants were taller and heavier but exhibited no more competitive ability than serpentine plants. The predictions that rapid height growth and biomass accumulation contribute significantly to competitive ability are not supported by our results. Although ecotypic differentiation has occurred between these A. millefolium populations, apparently in response to different soil types, the expression of these heritable differences can be masked by other environmental effects. There has been no apparent "trade-off" in these ecotypes between their response to the physical environment and their competitive ability.


Pyrimido-oxazepine as a versatile template for the development of inhibitors of specific kinases.
Pyrimido-oxazepine based sub-micromolar inhibitors (2-4) for Aurora and FLT-3 were designed and synthesized. These preliminary results supported the potential use of pyrimido-oxazepines as a versatile template for developing specific kinase inhibitors.


An assessment of university students and staff perceptions regarding the use of human urine as a valuable soil nutrient in South Africa.
The declines in soil fertility associated with insufficient commercial fertilizers have resulted in the use of organic manure (human urine and faeces) as a source of fertilizers for production and cultivation of crop plants. The aim of this study was to assess perceptions of students and workers at the University of Limpopo (Medunsa Campus) regarding the fertilizing effect of urine. A total of 225 questionnaires were administered to staff and students. The questionnaire sought to establish the knowledge, attitude and behavioural changes as regards the use of urine as a fertilizer for the cultivation of vegetables. Descriptive statistical analysis of the data indicated that 86.8% of the respondents were unaware of any human urine use as a fertilizer, 82.7% and 81.1% would not eat spinach and maize fertilized with urine respectively. Only 38.3% said they would eat vegetables fertilized with animal urine making it more tolerable as compared to human urine. Health reasons were given as the main reasons why respondents were unwilling to eat crops fertilized with human urine. However, 69.9% of the respondents [74.3% females, 69.9% students, 75.0% (27-36) age group] were willing to change their attitudes and unwillingness if they were better informed about the safety of human urine use for agricultural purposes. Education, awareness and reassurance on the importance and safety of urine would have to be done so that urine for agricultural purposes could become more acceptable to people.


[Semantics, epidemiology and semiology of stroke].
Stroke is a cerebrovascular disorder characterised by the sudden onset of symptoms and clinical signs. Each year, an estimated 140,000 people in France are hospitalised for stroke. Ischemic stroke is the most common kind of stroke, accounting for 80% of all cases. Haemorrhagic stroke accounts for about 20% of all strokes.


Sepsis Prediction Model for Determining Sepsis vs SIRS, qSOFA, and SOFA.
The Sepsis Prediction Model (SPM) is a proprietary decision support tool created by Epic Systems; it generates a predicting sepsis score (PSS). The model has not undergone validation against existing sepsis prediction tools, such as Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick Sepsis-Related Organ Failure Asessement (qSOFA). To assess the validity and timeliness of the SPM compared with SIRS, qSOFA, and SOFA. This retrospective cohort study included all adults admitted to 5 acute care hospitals in a single US health system between June 5, 2019, and December 31, 2020. Data analysis was conducted from March 2021 to February 2023. A sepsis event was defined as receipt of 4 or more days of antimicrobials, blood cultures collected within ±48 hours of initial antimicrobial, and at least 1 organ dysfunction as defined by the organ dysfunction criteria optimized for the electronic health record (eSOFA). Time zero was defined as 15 minutes prior to qualifying antimicrobial or blood culture order. Of 60 507 total admissions, 1663 (2.7%) met sepsis criteria, with 1324 electronic health record-confirmed sepsis (699 [52.8%] male patients; 298 [22.5%] Black patients; 46 [3.5%] Hispanic/Latinx patients; 945 [71.4%] White patients), 339 COVID-19 sepsis (183 [54.0%] male patients; 98 [28.9%] Black patients; 36 [10.6%] Hispanic/Latinx patients; and 189 [55.8%] White patients), and 58 844 (97.3%; 26 632 [45.2%] male patients; 12 698 [21.6%] Black patients; 3367 [5.7%] Hispanic/Latinx patients; 40 491 White patients) did not meet sepsis criteria. The median (IQR) age was 63 (51 to 73) years for electronic health record-confirmed sepsis, 69 (60 to 77) years for COVID-19 sepsis, and 60 (42 to 72) years for nonsepsis admissions. Within the vendor recommended threshold PSS range of 5 to 8, PSS of 8 or greater had the highest balanced accuracy for classifying a sepsis admission at 0.79 (95% CI, 0.78 to 0.80). Change in SOFA score of 2 or more had the highest sensitivity, at 0.97 (95% CI, 0.97 to 0.98). At a PSS of 8 or greater, median (IQR) time to score positivity from time zero was 68.00 (6.75 to 605.75) minutes. For SIRS, qSOFA, and SOFA, median (IQR) time to score positivity was 7.00 (-105.00 to 08.00) minutes, 74.00 (-22.25 to 599.25) minutes, and 28.00 (-108.50 to 134.00) minutes, respectively. In this cohort study of hospital admissions, balanced accuracy of the SPM outperformed other models at higher threshold PSS; however, application of the SPM in a clinical setting was limited by poor timeliness as a sepsis screening tool as compared to SIRS and SOFA.


Orbital alveolar soft part sarcoma: Histopathologic report of two cases.
Alveolar soft part sarcoma is considered as a distinct histopathological entity with rare cases reported from the orbit area. Two cases of alveolar soft part sarcomas occurring in the orbit of two patients along with their histopathologic findings are reported herewith. In both cases, the patients presented with eyelid swelling and proptosis. The diagnosis was made by incisional biopsies and histopathology. The literature is reviewed regarding occurrence of this tumor, its diagnosis and management.


Entobdella soleae--pointers to the future.
The biology of the monogenean skin parasite Entobdella soleae and its relationship with its host, the common sole (Solea solea), are probably better known than those of any other monogeneans. The author describes his early involvement with this parasite and the special features of parasite and host that make this relationship so suitable for parasitological studies. Aspects of the biology of E. soleae that have been investigated are briefly mentioned, but most of the paper is concerned with areas of the parasite's biology that remain a challenge to determine. Unresolved areas are as follows: (1) the identity of the factor (or factors) in host skin mucus that stimulates hatching of the parasite's eggs; (2) whether or not the larvae of the parasite are attracted to their host; (3) the nature of factors controlling the contrasting behaviour of adult parasites on the upper and lower surfaces of the host; (4) how nutrients are supplied to the remote regions of the haptor; (5) whether the host has any control via its immune system over parasite invasion success and survival; (6) how the parasite copes with the migratory habits of some sole populations, assuming that such populations are infested with the parasite. The intimacy of this parasite/host relationship is its most remarkable feature, the reflection of which, not surprisingly, is the greatly restricted host range of the parasite. E. soleae has been reported from only three host species, all highly specialised bottom-dwelling members of Solea. It is all the more surprising that relatives of E. soleae, such as Neobenedenia melleni, retain the ability to parasitise an enormous range of hosts. How this versatility is achieved remains to be seen.


Identification of an enteric adenovirus by immunoelectroosmophoresis (IEOP) technique.
Infantile gastroenteritis can be caused by several of the established adenovirus types. There are also adenoviruses that defy in vitro cultivation but have been recognized by electron microscopy. One isolate of these viruses, which have been designated enteric adenoviruses, has been characterized. Several of the established adenovirus types are shed in stools over long periods. The conditions for direct identification of enteric adenoviruses by immunoelectroosmophoresis (IEOP) have therefore been evaluated. Application of this technique requires highly specific reagents. However, a high prevalence of antibodies in rabbits reacting with human rotavirus was noted. For these reasons, immunoadsorbent purified antibodies were prepared. Because of the difficulty in purifying immunogens from stools, an immunization procedure characterized by immunization with adenovirus subunits bound to affinity chromatography beads was elaborated. An identification procedure for adenoviruses causing infantile gastroenteritis based a) on IEOP using group-specific and monospecific antibodies and b) on the determination of the in vitro cultivatability is suggested.


Co-existence of alpha-glucosidase-inhibitory and liver X receptor-regulatory activities and their separation by structural development.
Liver X receptors (LXR), which were originally reported as oxysterol-activated nuclear receptors, were recently found to recognize glucose as a physiological ligand. On this basis, we have already developed novel LXR antagonists based upon alpha-glucosidase inhibitors derived from thalidomide. Here, to clarify the relationship between alpha-glucosidase inhibition and LXR modulation, we investigate the alpha-glucosidase-inhibitory activity of typical LXR ligands and the LXR-modulating activity of typical alpha-glucosidase inhibitors. Although there were some exceptions, co-existence of LXR-regulatory and alpha-glucosidase-inhibitory activities seemed to be rather general among the examined compounds. The LXR ligands were found to be non-competitive alpha-glucosidase inhibitors, suggesting that it might be possible to separate the two activities. To test this idea, we focused on riccardin C, a naturally occurring LXR ligand, which we found here to be a potent alpha-glucosidase inhibitor as well. Structural development of riccardin C afforded novel LXR antagonists lacking alpha-glucosidase-inhibitory activity, 19c and 19f, and a LXRalpha-selective antagonist, 22.


MS Analysis of DNA Modifications in Urinary/Body Fluids.
Analytical techniques based on mass spectrometry allow to analyze DNA modifications in body fluids. Here we describe two chromatographic methods that can be used for the simultaneous determination of the modified DNA bases and nucleosides in the same urine sample: isotope-dilution automated online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS) and high-performance liquid chromatography coupled with gas chromatography and mass spectrometry (HPLC/GC/MS).


Partnership Through Integration: Perianesthesia Policy Standardization.
To develop system-wide perianesthesia policies, through partnerships, across 11 acute care hospitals and 1 ambulatory surgery center. A partnership culture was created and maintained throughout the development and integration of multiple site-based policies into system policies. Policies were built using evidence-based practice and professional organizational standards with an emphasis on quality, safety, and standardization of patient care. Early and ongoing partnerships with key stakeholders were maintained in order to effectively develop the policies. More than 50 independent policies across 11 acute care hospitals and 1 ambulatory surgery center were integrated and updated into 4 main perianesthesia nursing policies. Flexibility and partnership with key stakeholders throughout the policy process was instrumental for early detection of barriers and the successful development of perianesthesia nursing policies.


[Fluorescence in situ hybridization in the diagnosis of aggressive B-cell lymphomas].
The introduction of new lymphoma entities that are defined by chromosomal rearrangements has led to changes concerning the diagnostic algorithms in routine hematopathology, particularly for the large group of aggressive B‑cell lymphomas. The new, genetically defined entity high-grade B‑cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit lymphoma) is morphologically heterogenous and comprises lymphomas with the morphology of a diffuse large B‑cell lymphoma (DLBCL), but also cases with blastoid appearance as well as intermediate/Burkitt-like morphology. This implies a cytogenetic analysis for the final classification of aggressive lymphomas with DLBCL morphology, which constitute the most common lymphomas in daily practice. This analysis is currently most efficiently performed via a sequential fluorescence in situ hybridization (FISH) approach, with an initial MYC-FISH, that is followed (if required, i.e., if a MYC rearrangement is detected) by an analysis regarding a BCL2- and BCL6-chromosomal rearrangement. In addition, the update of the fourth edition of the WHO classification for hematopoietic neoplasms introduced additional lymphoma subgroups that are defined by chromosomal rearrangements, such as Burkitt-like lymphoma with 11q aberration as well as large B cell lymphoma with IRF4 rearrangement. Therefore, FISH currently plays an important role in the diagnostic armamentarium in routine diagnostic hematopathology.


GABA(A) receptor chloride channels are involved in the neuroprotective role of GABA following oxygen and glucose deprivation in the rat cerebral cortex but not in the hippocampus.
Assays on "ex vivo" sections of rat hippocampus and rat cerebral cortex, subjected to oxygen and glucose deprivation (OGD) and a three-hour reperfusion-like (RL) recovery, were performed in the presence of either GABA or the GABA(A) receptor binding site antagonist, bicuculline. Lactate dehydrogenase (LDH) and propidium iodide were used to quantify cell mortality. We also measured, using real-time quantitative polymerase chain reaction (qPCR), the early transcriptional response of a number of genes of the glutamatergic and GABAergic systems. Specifically, glial pre- and post-synaptic glutamatergic transporters (namely GLAST1a, EAAC-1, GLT-1 and VGLUT1), three GABAA receptor subunits (α1, β2 and γ2), and the GABAergic presynaptic marker, glutamic acid decarboxylase (GAD65), were studied. Mortality assays revealed that GABAA receptor chloride channels play an important role in the neuroprotective effect of GABA in the cerebral cortex, but have a much smaller effect in the hippocampus. We also found that GABA reverses the OGD-dependent decrease in GABA(A) receptor transcript levels, as well as mRNA levels of the membrane and vesicular glutamate transporter genes. Based on the markers used, we conclude that OGD results in differential responses in the GABAergic presynaptic and postsynaptic systems.


Expression of mammalian G protein-coupled receptors in Caenorhabditis elegans.
Constituting the largest group of membrane proteins identified in the human genome, G protein-coupled receptors (GPCRs) help control many physiological processes by responding to various stimuli. As targets for more than 40% of all prescribed pharmaceuticals, detailed understanding of GPCR structures is vital for the design and development of more specific medications and improved patient therapies. But structural information for membrane proteins and GPCRs, in particular, is limited despite considerable interest. The major impediment to obtaining sufficient quantities of highly purified GPCRs in their native form for crystallization lies in their low tissue levels, poor yields, and stability. The only exception is rhodopsin, which is abundantly expressed in the eye and stabilized by its covalently bound chromophore, 11-cis-retinal. Expression systems and purification protocols have yet to be developed for all other GPCRs. Here, we present a novel expression system for human GPCRs in Caenorhabditis elegans that produces sufficient amounts of recombinant proteins to allow their biochemical and structural characterization.


Degradation of thymopentin by human lymphocytes: evidence for aminopeptidase activity.
Thymopentin (Arg-Lys-Asp-Val-Tyr) was shown to be degraded in vitro by human lymphocytes into two main fragments; the tetrapeptide Lys-Asp-Val-Tyr and the tripeptide Asp-Val-Tyr. Degradation products were identified by HPLC and amino-acid analysis. Analysis of the time-course of degradation revealed a 'stepwise' degradative event beginning at the N-terminal. The degradation of thymopentin after the first 10 min, as well as the formation of the tetrapeptide (5-30 min) were essentially curvilinear. Degradation of the tripeptide, was linear. Upon screening a panel of compounds that inhibit enzymatic activity, bestatin, amastatin and 1,10-phenanthroline were shown to be the most effective. Bestatin and amastatin caused an 85-90% inhibition of thymopentin degrading activity with IC50 values of 7.1 x 10(-6) M and 4.5 x 10(-9) M, respectively. 1,10-Phenanthroline completely inhibited the degradative process with an IC50 of 2 x 10(-4) M. When the tetrapeptide Lys-Asp-Val-Tyr was used as the starting substrate, similar IC50 values were seen for amastatin, bestatin and 1,10-phenanthroline. The importance of divalent metal ions in the degradative event was demonstrated not only by the effect of 1,10-phenanthroline, but also by the ability of Zn2+ and Co2+ to reverse the inhibition of 1,10-phenanthroline (at its IC50) to activities near control values (no inhibitor). These data strongly suggest that an aminopeptidase(s) is responsible for the degradative activity.


cDNA cloning, chromosomal localization and expression pattern analysis of human LIM-homeobox gene LHX4.
LHX4 gene is a member of the LIM-homeobox gene family and plays a critical role in the development of motor neurons. We have isolated a cDNA of human LHX4 from a library of the adult human spinal cord. Its sequence is 92% homologous to that of the mouse Lhx4. The genomic structure of the LHX4 gene and its chromosomal localization were determined. The gene was mapped on human chromosome 1q 24.1-1q 24.3 and composed of six exons. The homeodomain was encoded by two exons, exons 4 and 5. The first LIM domain was coded by exon 2, and the second by exon 3. Human MTE Array was used to study the expression profile of LHX4 in 72 human tissues. The expression was specific in the CNS including the fetal brain, the spinal cord, and the cerebral cortex. In situ hybridization of the adult rodent CNS showed the abundant expression of LHX4 in the cerebral cortex and motor neurons of the spinal cord. Our results suggest that LHX4 may play a role in the CNS, especially the neocortex and the spinal cord, and provide a basis to investigate potential involvement of the LHX4 gene in human diseases.


Reviewing the experimental and mathematical factors involved in tight binding inhibitors Ki values determination: The bi-functional protease inhibitor SmCI as a test model.
Different methodologies for determining the dissociation equilibrium constant (Ki) of protein tight binding inhibitors are frequently found in the scientific literature. Taking into account that the Ki value is the main parameter characterizing the inhibition strength, its determination often represents the first step during the characterization of a potential drug. The purpose of this review is to summarize the current information related to tight binding inhibitors Ki values determination and discuss about the importance of different factors as the enzyme concentration, the inhibitor concentration dilution series, the enzyme-inhibitor incubation time and the dose-response data mathematical fitting. For this aim, the bi-functional SmCI protease inhibitor is used as a tool for exemplifying the experimental and mathematical steps performed during tight binding inhibitors Ki values determination. In addition, the natural and the different recombinant forms of SmCI were used to go deeply into the comparison of some mathematic approaches that are frequently used in the literature. Finally, other biochemical techniques that could be potentially used for tight binding inhibitors Ki values determination are also commented.


Selenium as a potential fungicide could protect oilseed rape leaves from Sclerotinia sclerotiorum infection.
Sclerotinia sclerotiorum (S. sclerotiorum) is a soil-borne pathogen causing serious damage to the yield of oilseed rape. Selenium (Se) acted as a beneficial element for plants, and also proved to inhibit the growth of plant pathogens. However, whether Se could reduce S. sclerotiorum infection in oilseed rape, the related mechanism is still unclear. In this study, proper Se levels (0.1 mg/kg and 0.5 mg/kg) applied in soil decreased the lesion diameter and incidence of S. sclerotiorum in rape leaves. Se enfeebled the decrease of net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (Tr), and maintained leaf cell structure. Se enhanced the antioxidant system of leaves, as evidenced by the maintenance of mitochondrial function, reduction of reactive oxygen species (ROS) accumulation and malondialdehyde (MDA) content, and the improvement of antioxidant enzyme activities including catalase (CAT), polyphenol oxidase (PPO) and peroxidase (POD). The upregulated defense gene expressions (CHI, ESD1, NPR1 and PDF1.2) of leaves were also observed under Se treatments. Furthermore, metabolome analysis revealed that Se promoted the metabolism of energy and amino acids in leaves infected with S. sclerotiorum. These findings inferred that Se could act as a potential eco-fungicide to protect oilseed rape leaves from S. sclerotiorum attack. The result arising from this study not only introduces an ecological method to control S. sclerotiorum, but also provides a deep insight into microelement for plant protection.


Superiority of intensity-modulated radiation therapy in nasopharyngeal carcinoma with skull-base invasion.
To compare the clinical results and functional outcomes between two-dimensional conventional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC) with skull-base invasion. A total of 1258 patients were subclassified into two groups: mild skull-base invasion group (792; 63%) and severe skull-base invasion group (466; 37%). Patients were pair matched (1:1 ratio) using six clinical factors into 2DRT or IMRT groups. The Kaplan-Meier method and Cox regression model were performed to assess overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Toxicities were evaluated. IMRT significantly improved four-year OS compared with 2DRT (65.6% vs. 81.8%, P = 0.000), DFS (57.3% vs. 73.3%, P = 0.000) and LRRFS (76.5% vs. 87.5%, P = 0.003) in NPC with severe skull-base invasion, but similar results were observed in patients with mild skull-base invasion (P > 0.05). In patients with severe invasion, radiation therapy techniques were found to be an independent prognostic factor for OS (HR = 0.457, P = 0.000), DFS (HR = 0.547, P = 0.000) and LRRFS (HR = 0.503, P = 0.004). IMRT was associated with better OS. In subgroups analysis, IMRT group also had a better survival in OS, DFS (P < 0.05 for all rates) for patients received concurrent chemotherapy and sequential chemotherapy compared to 2DRT in the severe invasion group. The IMRT group displayed lower incidence of mucositis, xerostomia, trismus (< 1 cm) and temporal lobe necrosis than the 2DRT group. IMRT significantly improved patient survival compared with 2DRT in NPC patients with severe skull-base invasion, but a similar survival rate was noted in mild invasion patients. Chemotherapy can improve survival in NPC patients with severe invasion. Among the two therapies, IMRT significantly decreased therapy-related toxicity.


Unexpected emergence of manifest preexcitation following transcatheter ablation of concealed accessory pathways.
The basis for anterograde or retrograde unidirectional block of accessory pathways still remains a controversial issue. Four of 19 consecutive patients (1 male, 3 female; ages 27 to 34 years) who underwent transcatheter ablation of concealed accessory pathways developed manifest preexcitation after the ablation. The location of the concealed accessory pathways in these four patients were right lateral, left posteroseptal, left posterolateral, and left lateral. Radiofrequency current was used in three of the four patients and high energy direct current in one patient. After ablation, manifest preexcitation was observed in these four patients for the first time. Manifest preexcitation developed immediately after ablation in two of the four patients and after 4 and 14 days in the other two. Detailed endocardial mapping revealed that the manifest preexcitation originated from the same location as the concealed pathways. Subsequently, catheter ablation was successfully performed in three of the four patients using radiofrequency current. One patient underwent successful surgical ablation. No recurrence of preexcitation was observed during a follow-up period of 9 to 38 months. All patients remained free of arrhythmias. The basis for this unexpected emergence of preexcitation in these patients with only retrograde conducting accessory pathways deserves further investigation. Although not compared in the present study, this phenomenon has not been reported in patients who underwent surgical interruption of accessory pathways. We postulate that a lesion at the site of insertion of the accessory pathway had modified the anterograde conduction capacity.


Intraocular lens power calculation following laser refractive surgery.
Refractive outcomes following cataract surgery in patients that have previously undergone laser refractive surgery have traditionally been underwhelming. This is related to several key issues including the preoperative assessment (keratometry) and intraocular lens power calculations. Peer-reviewed literature is overwhelmed by the influx of methodology to manipulate the corneal or intraocular lens (IOL) powers following refractive surgery. This would suggest that the optimal derivative formula has yet been introduced. This review discusses the problems facing surgeons approaching IOL calculations in these post-refractive laser patients, the existing formulae and programs to address these concerns. Prior published outcomes will be reviewed.


Rate adaptive atrial pacing in the bradycardia tachycardia syndrome.
In 42 patients (26 men, 16 women; mean age 69 +/- 10 years), who were paced and medicated with antiarrhythmic drugs for the bradycardia tachycardia syndrome, chronotropic response and AV conduction with rapid atrial pacing during exercise were studied. Patients were included if they had no second- or third-degree AV block, no complete bundle branch or bifascicular block, and a PQ interval < or = 240 ms during sinus rhythm at rest. The interval between the atrial spike and the following Q wave (SQ) was measured in the supine position at rest with an AAI pacing rate of 5 beats/min above the sinus rate (SQ-R + 5), and at the end of exercise with 110 beats/min (SQ-E110). Bicycle ergometry was performed using the Chronotropic Assessment Exercise Protocol with the pacemakers being programmed to AAI with a fixed rate of 60 beats/min. Chronotropic incompetence was defined as peak exercise heart rate: (1) < 100 beats/min; (2) < 75% of the maximum predicted heart rate; or (3) the heart rate at half the maximum workload < 60 + 2 beats/min per mL O2/kg per minute (calculated O2 consumption). During exercise, one patient developed atrial fibrillation. Chronotropic incompetence was present in 71% (29/41) of the patients according to definition 2, and in 76% (31/41) according to definition 1 or 3. Ten out of 41 patients (24%) exhibited a second-degree AV block with atrial pacing at 110 beats/min at the end of exercise. Only 9 out of the remaining 31 patients (29%) showed a physiological adaptation of the SQ-E110, and 21 patients (68%) exhibited a paradoxical increase of the SQ interval with rapid atrial pacing at the end of exercise as compared to the SQ-R + 5. These observations indicate that the pacing system to be used in most patients paced and medicated for the bradycardia tachycardia syndrome should be dual chamber, and the option of rate adaptation should be considered.


The association of normal-range serum phosphorus with immunoglobulin A nephropathy progression: a retrospective cohort study.
The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73-1.04 mmol/L; second tertile: 1.04-1.21 mmol/L; third tertile: 1.21-1.60 mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. During a median 16 month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953-1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522-92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019-87.165, P = 0.048). Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy.


The mechanism of bone repair: Stem cells in the periosteum dedicated to bridging a large gap.
Bone repair requires the mobilization of stem cells from outer periosteum and inner bone marrow. A study by Jeffery et al.1 shows that periosteal stem cells are dedicated to repairing a large defect and regenerating both bone and marrow stroma.


Greater myofibrillar protein synthesis following weight-bearing activity in obese old compared with non-obese old and young individuals.
The mechanisms through which obesity impacts age-related muscle mass regulation are unclear. In the present study, rates of integrated myofibrillar protein synthesis (iMyoPS) were measured over 48-h prior-to and following a 45-min treadmill walk in 10 older-obese (O-OB, body fat[%]: 33 ± 3%), 10 older-non-obese (O-NO, 20 ± 3%), and 15 younger-non-obese (Y-NO, 13 ± 5%) individuals. Surface electromyography was used to determine thigh muscle "activation". Quadriceps cross-sectional area (CSA), volume, and intramuscular thigh fat fraction (ITFF) were measured by magnetic resonance imaging. Quadriceps maximal voluntary contraction (MVC) was measured by dynamometry. Quadriceps CSA and volume were greater (muscle volume, Y-NO: 1182 ± 232 cm3; O-NO: 869 ± 155 cm3; O-OB: 881 ± 212 cm3, P < 0.01) and ITFF significantly lower (m. vastus lateralis, Y-NO: 3.0 ± 1.0%; O-NO: 4.0 ± 0.9%; O-OB: 9.1 ± 2.6%, P ≤ 0.03) in Y-NO compared with O-NO and O-OB, with no difference between O-NO and O-OB in quadriceps CSA and volume. ITFF was significantly higher in O-OB compared with O-NO. Relative MVC was lower in O-OB compared with Y-NO and O-NO (Y-NO: 5.5 ± 1.6 n·m/kg-1; O-NO: 3.9 ± 1.0 n·m/kg-1; O-OB: 2.9 ± 1.1 n·m/kg-1, P < 0.0001). Thigh muscle "activation" during the treadmill walk was greater in O-OB compared with Y-NO and O-NO (Y-NO: 30.5 ± 13.5%; O-NO: 35.8 ± 19.7%; O-OB: 68.3 ± 32.3%, P < 0.01). Habitual iMyoPS did not differ between groups, whereas iMyoPS was significantly elevated over 48-h post-walk in O-OB (+ 38.6 ± 1.2%·day-1, P < 0.01) but not Y-NO or O-NO (+ 11.4 ± 1.1%·day-1 and + 17.1 ± 1.1%·day-1, respectively, both P > 0.271). Equivalent muscle mass in O-OB may be explained by the muscle anabolic response to weight-bearing activity, whereas the age-related decline in indices of muscle quality appears to be exacerbated in O-OB and warrants further exploration.


The MERG Suite: Tools for discovering competencies and associated learning resources.
As the demands for competency-based education grow, the need for standards-based tools to allow for publishing and discovery of competency-based learning content is more pressing. This project focused on developing federated discovery services for competency-based medical e-learning content. We built a tool suite for authoring and discovery of medical e-learning metadata. The end-user usability of the tool suite was evaluated through a web-based survey. The suite, implemented as an open-source system, was evaluated to identify areas for improvement. The MERG suite is a starting point for organizations implementing competency-based e-learning resources.


Classification of porcine enteroviruses by antigenic analysis and cytopathic effects in tissue culture: description of 3 new serotypes.
Porcine enteroviruses isolated in the United Kingdom between 1972 and 1976 were compared with the 8 serotypes previously described and with human coxsackie B virus types 1 to 6 for ability to grow in different cell lines. This allowed the classification of all strains into 3 broad groups according to type of cytopathic effect in IBRS-2 cells and further subdivision on the basis of production of cytopathic effect in BHK 21, HeLa and VERO cells. None of the porcine enterovirus strains was neutralized by antisera to human enteroviruses (Lim Benyesh-Melnick Pools) with the exception of swine vesicular disease virus, which was neutralised by coxsackie B5 antiserum. Antisera prepared either in gnotobiotic pigs or in guinea pigs against the 8 porcine enterovirus serotypes failed to neutralize 9 isolates which could be classified into 3 new serotypes, for which Nos. 9, 10 and 11 are proposed. Guinea pig sera could be used as an alternative to gnotobiotic pig sera for type differentiation.


Human papillomavirus detection from the female genital tract: combined vs. separate scrape methods.
Because genital human papillomavirus (HPV) infections tend to be multifocal, it was studied how effective one combined specimen is in detecting HPV-DNA from the lower female genital tract. The study population consisted of 50 patients referred to a colposcopy clinic for a suspected condylomatous and/or dysplastic lesion. From half of the patients, a separate scrape from the cervix, vagina and vulva was taken first followed by a combined scrape representing all the genital sites, and from the other half, vice versa. HPV-DNA (types 6, 11, 16 and 18) was identified using the AffiProbe hybridisation test. Thirty-six specimens collected from 17 patients were positive for HPV-DNA. A multifocal infection was demonstrated in at least 11/17 (65%) HPV-DNA positive patients. The combined scrape was the most informative specimen, revealing 75% of all HPV-DNA-positive patients. It was concluded that HPV-DNA can reliably be detected from the female genital tract in a simple way from one combined specimen.


Coumarin-based fluorescent probes toward viscosity in mitochondrion/lysosome.
Viscosity is an important microenvironmental indicator that plays an important role in the process of information transmission in various regions. Herein, two coumarin-based viscosity-sensitive fluorescent probes (CHB, CHN) were synthesized and the photophysical properties of the two probes were studied. The fluorescence quantum yields of CHB and CHN in glycerol can be as high as 25.2% and 18.3% respectively. The two probes can linearly detect viscosity in the viscosity logarithm range of 0.83-2.07, which is not interfered with pH, metal ions, anions and biomolecules. Fluorescent confocal cell experiments show CHB and CHN have good targeting ability to mitochondrion, lysosome, Endoplasmic reticulum and Golgi apparatus, and can be used to detect viscosity in mitochondrion/lysosome.


Optimal boundary detection method and window settings for coronary atherosclerotic plaque volume analysis in coronary computed tomography angiography: comparison with intravascular ultrasound.
To evaluate optimal methodology for quantitative plaque volume analysis by coronary CT angiography (QCT). Fifty-one coronary artery segments were evaluated and contour measurements based on two different methods [(1) no gap, or (2) fixed 0.3-mm gap between inner and outer boundary] were compared with intravascular ultrasound (IVUS). In addition, three different window width (WW) and level (WL) settings [fixed (740/220) Hounsfield unit (HU), adjusted (155 % and 65 % of mean luminal intensity of the segment, and aorta adjusted (155 % and 65 % of mean luminal intensity of central aorta)] were used for semiautomated plaque volume analysis. For boundary detection, the no gap method led to underestimation compared with IVUS (105.4 ± 82.3 vs. 136.1 ± 72.8 mm(3), p < 0.001), while fixed 0.3-mm gap showed no difference between IVUS and QCT (136.1 ± 72.8 vs. 139.8 ± 93.9 mm(3), p = 0.50). Comparison of the three different window settings demonstrated that the aorta adjusted setting underestimated (120.5 ± 74.3 vs. 136.1 ± 72.8 mm(3), p = 0.003), while fixed setting showed the least mean difference compared with IVUS (3.8 ± 39.8 mm(3), p = 0.50). For plaque volumetric assessment, optimal results were obtained with fixed 0.3-mm gap with fixed HU setting (740/220). • Quantitative plaque volume analysis by coronary CT angiography has recently emerged. • Different boundary detection methods and window width and level settings were evaluated. • Fixed 0.3-mm gap with fixed HU setting (740/220) afforded optimal results.


Hydroxyapatite-coated femoral stems in primary total hip arthroplasty: a meta-analysis of randomized controlled trials.
Controversy exists over the use of hydroxyapatite (HA)-coated femoral stems in primary total hip arthroplasty (THA). We conducted a meta-analysis of randomized controlled trials (RCT) to compare the clinical and radiologic outcomes of primary THA using HA-coated versus non-HA-coated femoral stems. Databases including MEDLINE, EMBASE and the Cochrane Library were searched to find relevant RCTs comparing HA-coated versus non-HA-coated femoral stems in primary THA. Data analyses were performed using RevMan 5.0 (The Cochrane Collaboration). Seven studies (792 hips) met the inclusion criteria. The pooled weighted mean difference (WMD) for the postoperative Harris hip score was 3.04 (95% CI: -4.47 to 10.54, P = 0.43). The cumulative risk ratios (RR) for the presence of endosteal condensation and radioactive lines were 1.02 (95% CI: 0.93 to 1.12, P = 0.64) and 1.01 (95% CI: 0.90 to 1.14, P = 0.81), respectively. This meta-analysis demonstrates that the use of HA-coated femoral stems in primary THA has no clinical or radiological benefits.


Efficiency of Ipratropium Bromide and Albuterol Deposition in the Lung Delivered via a Soft Mist Inhaler or Chlorofluorocarbon Metered-Dose Inhaler.
The propellant-free Combivent Respimat Soft Mist Inhaler (CVT-R) was developed to replace the chlorofluorocarbon-propelled Combivent metered-dose inhaler (CVT-MDI). This steady-state pharmacokinetic (PK) substudy evaluated drug lung-delivery efficiency, using data from two phase III safety and efficacy trials. PK parameters were obtained from well-controlled population PK analyses. Area under the plasma concentration-time curve (AUC), maximum observed plasma concentration (C(max)), and minimum observed plasma concentration (C(min)) showed systemic exposure to ipratropium bromide and albuterol delivered via the CVT-R was proportional to ex-mouthpiece delivered dose. Although the labeled dose of ipratropium bromide in the CVT-R was half that in the CVT-MDI, the systemic exposure was comparable. No PK interaction for the ipratropium bromide and albuterol Respimat drug components was demonstrated. Ipratropium bromide alone resulted in similar exposure to the combination of ipratropium bromide and albuterol. These results show that CVT-R delivers drug more efficiently to the lung than CVT-MDI.


Intrinsic conformational flexibility of acetylcholinesterase.
Proteins have been metaphorically described--due to the introduction and extraordinary advances in biomolecular dynamics and computational biophysics over the past decades--as "kicking and screaming" molecules [G. Weber, Adv. Protein Chem. 29 (1975) 1-83]. In fact, dynamic fluctuations in protein structural conformation have been known to play an important role in protein function. However, fundamental mechanisms by which protein fluctuations couple with catalytic function of particular enzymes remain poorly understood. To understand the dynamical properties of acetylcholinesterase (AChE) in rapid termination of cationic neurotransmitter, acetylcholine at neurosynaptic junctions, multiple molecular dynamics (MD) trajectories of AChE in the presence and absence of its inhibitors [J.M. Bui, J.A. McCammon, Proc. Natl. Acad. Sci. U.S.A. 103 (2006) 15451-15456; J.M. Bui, Z. Radic, P. Taylor, J.A. McCammon, Biophys. J. 90 (2006) 3280-3287; J.M. Bui, K. Tai, J.A. McCammon, J. Am. Chem. Soc. 126 (2004) 7198-7205; J.M. Bui, R.H. Henchman, J.A. McCammon, Biophys. J. 85 (2003) 2267-2272] have been conducted and correlated with its inhibitory mechanisms. The intrinsic flexibilities of AChE, particularly of the long omega loop, are important in facilitating the ligand's inhibition of the enzyme.


Percutaneous coronary interventions in octogenarians. glycoprotein IIb/IIIa receptor inhibitors' safety profile.
This study was designed to evaluate the safety profile of glycoprotein IIb/IIIa receptor inhibitors (GPI) in octogenarians undergoing percutaneous coronary intervention (PCI). Patients > or =80 years old constitute the fastest growing segment of the U.S. population and have a high prevalence of coronary artery disease. Few data exist regarding the use of GPI during PCI in octogenarians, as these patients have been excluded from randomized clinical trials of GPI. Consecutive patients > or =80 years old undergoing PCI between January 1998 and June 2001 were evaluated for clinical outcomes and bleeding complications. One thousand three hundred and ninety two of 14,308 patients (9.7%) undergoing PCI were > or =80 years old. Of these, 459 of 1,392 (33%) of the patients were treated with GPI. Octogenarians treated with GPI were more likely to present with acute coronary syndrome or infarction, receive stents, require an intra-aortic balloon pump, or undergo multi-vessel PCI. Glycoprotein receptor inhibitor use was associated with a higher rate of bleeding, but the transfusion rate was similar to that in patients who did not receive GPI (9.8% vs. 8.6%, p = NS). No cases of intracranial hemorrhage were observed. By multivariate analysis, GPI treatment was associated with longer hospitalization but did not independently predict the need for transfusion or affect mortality. Octogenarians have a high incidence of bleeding and need for transfusion after PCI. Although the use of GPI was associated with more access and non-access site bleeding and longer hospital stay, GPI treatment does not significantly increase the risk of transfusion or intracranial hemorrhage in this non-randomized cohort.


Inter- vs intra-individual variation and temporal repeatability of escape responses in the coral reef fish Amblyglyphidodon curacao.
Fast-start escape responses are critical behaviours used by fishes during predator-prey encounters and some interactions with hetero- and conspecifics. In experimental studies, escape responses are often measured once per individual and considered representative of maximum performance. However, few studies have compared variability and repeatability in escape performances within and among individuals. Using the tropical damselfish Amblyglyphidodon curacao, we quantified inter- and intra-individual variation in behavioural and kinematic components of escape performance during repeated presentations of a stimulus at 15 min intervals. Individual maximum escape performance was repeatable through time, but there was considerable variation in the magnitude of responses both among and within fish. We found no evidence of habituation or fatigue due to repeated stimulations, suggesting that fish can be stimulated multiple times to ensure that an accurate estimate of maximum escape performance is obtained.


Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1.
Vascular endothelial cell growth factor (VEGF) is a key regulator of vascular permeability. Herein we aim to understand how acute and chronic exposures of VEGF induce different levels of vascular permeability. We demonstrate that chronic VEGF exposure leads to decreased phosphorylation of VEGFR2 and c-Src as well as steady increases of nitric oxide (NO) as compared to that of acute exposure. Utilizing heat-inducible VEGF transgenic zebrafish (Danio rerio) and establishing an algorithm incorporating segmentation techniques for quantification, we monitored acute and chronic VEGF-induced vascular hyperpermeability in real time. Importantly, dimethylarginine dimethylaminohydrolase-1 (DDAH1), an enzyme essential for NO generation, was shown to play essential roles in both acute and chronic vascular permeability in cultured human cells, zebrafish model, and Miles assay. Taken together, our data reveal acute and chronic VEGF exposures induce divergent signaling pathways and identify DDAH1 as a critical player and potentially a therapeutic target of vascular hyperpermeability-mediated pathogenesis.


A stage in glycolysis controls the metabolic adjustments of vertebrate rod photoreceptors upon illumination.
The factors affecting the metabolic adjustments of toad rod photoreceptors were studied by monitoring the oxygen utilization of excised retinas and by measuring rod outer segment ATP and GTP concentrations. Respiratory adjustments upon illumination were observed when glucose or fructose was provided in the perfusate, but not when a glycolytic inhibitor was added to the perfusate containing glucose and pyruvate, or when a substrate beyond glycolysis or from a later stage of glycolysis was substituted for glucose. The amplitudes of the respiratory adjustments to illumination were dependent on the concentration of glucose in the perfusate. The ATP and GTP concentration changes were dependent on respiratory adjustments, including glycolytic effects, and on the levels of illumination. The data suggest a control point within glycolysis for light-induced adjustments of respiration, possibly at phosphofructokinase.


The expression of high mobility group box 1 is associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.
The objective is to explore the expression of high mobility group box 1 (HMGB1) in esophageal squamous cell carcinoma (ESCC) and its relationship with lymph node metastasis and the prognosis of patients as well as possible mechanism. The expression of HMGB1, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in ESCC tissues, which were obtained from 72 patients who underwent radical esophagectomy, was detected through immunohistochemistry, firstly. The correlations between HMGB1 and VEGF-C, and micro-lymphatic vessel density (MLD), and lymph node metastasis, and the prognosis of patients, were analyzed by statistic analysis. The plasmid of small interference RNA (siRNA) targeting HMGB1, giving siHMGB1, was transfected into exponentially growing KYSE150 human esophageal squamous cancer cells and the expression of HMGB1 mRNA and protein was observed by Real-time PCR and Western Blot and the expression of VEGF-C was examined by ELISA. HMGB1 expressed highly in the nuclei and cytoplasm of carcinoma cells as well as the extracellular space in ESCC and was associated with lymph node metastasis, MLD, the expression of VEGF-C, TNM stage and the prognosis of patients (P < 0.05 or P < 0.01). In vitro, siHMGB1 inhibited the expression of HMGB1 mRNA and protein and the secretion of VEGF-C in KYSE150 cells. In ESCC, HMGB1 expresses highly and affects the prognosis of patients through regulating the expression of VEGF-C to promote lymphangiogenesis and lymph node metastasis, and HMGB1 might serve as the marker of progression and potential target for anti-lymphangiogenesis therapy.


Normal levels of lymphotoxin secretion by freshly isolated and refrigerated human peripheral blood lymphocytes.
Lymphocytes obtained by Ficoll-Hypaque density gradient centrifugation of leukocytes from 40 blood bank donors were incubated at 10(6) cells/ml for 24 h with 5 micrograms phytohemagglutinin/ml serum-free RPMI 1640 medium and secreted 34 +/- 6 U lymphotoxin/ml and 52 +/- 29 U interferon/ml. Addition of 5% fetal bovine serum (FBS) or acid-citrate-dextrose treated autologous plasma (AP) augmented lymphotoxin secretion 2-fold and interferon secretion 6-8-fold. Lymphotoxin alone was secreted in 39% of serum free cultures. Both lymphotoxin and interferon were secreted in the presence of FBS or AP. Lymphocytes refrigerated at 4 degrees C for 18 h secreted upon serum-free culture similar levels of lymphotoxin as fresh cells but cultures secreting lymphotoxin alone increased from 39 to 77%. Lymphotoxin secretion by refrigerated lymphocytes was similar in the presence or absence of FBS or AP. Interferon secretion by refrigerated lymphocytes in the presence of FBS or AP, however, increased 30-40-fold approaching levels produced by freshly isolated cells and indicating that the modulatory effects of refrigeration, FBS, and AP affected interferon not lymphotoxin secretion. The levels of lymphotoxin and interferon secreted by lymphocyte populations producing both lymphokines, furthermore, varied independently of one another providing additional evidence for the dissociability of their secretion yet possible dependence of interferon upon lymphotoxin secretion. The ability to reliably quantitate lymphotoxin secretion using refrigerated lymphocytes permits transport of lymphocytes to laboratories performing quantitative bioassay of the lymphokine. This should facilitate further evaluation of the presence and role of lymphotoxin in immunopathological and other disease states.


Curettage or operative hysteroscopy in the treatment of cesarean scar pregnancy.
To compare the clinical effects of dilatation and curettage (D&C) regimen and operative hysteroscopy coupled with curettage regimen in the treatment of cesarean scar pregnancy (CSP) following preventive uterine artery embolization (UAE). Thirty-three women were treated with D&C after UAE (group A) and 33 women were treated with operative hysteroscopy coupled with curettage after UAE (group B). The clinical outcomes of the two groups were compared. There was no significant difference between the two groups with respect to the success rate, the intraoperative blood loss, the hysterectomy rate, the hospitalization time, the decline of serum β-hCG after surgery, the time of serum β-hCG resolution, the time of vaginal bleeding after surgery, the time to CSP mass disappearance, and the subsequent intrauterine pregnancies. The hospitalization cost in group B was higher than group A. Both D&C and operative hysteroscopy coupled with curettage were successful in terminating a CSP. Hysteroscopy coupled with curettage regimen did not have significant advantages and good prognosis in dealing with the gestational sac type of CSP following preventive UAE compared with D&C regimen. Treatment should be individualized and several conditions must be considered.


Hormone-dependent phosphorylation of the glucocorticoid receptor occurs mainly in the amino-terminal transactivation domain.
Phosphorylation of glucocorticoid receptors is increased by hormone binding and has been implicated in transcriptional regulation. We performed a phosphoamino acid analysis and identified the phosphorylated regions of the glucocorticoid receptor with respect to its functional domains before and after hormone activation. Receptor was isolated by immunoprecipitation from [32P]orthophosphate-labeled FTO 2B rat hepatoma cells grown in the absence or presence of glucocorticoids. The receptor contained mainly phosphoserine, with little phosphothreonine and no phosphotyrosine. Partial proteolysis of receptor from hormone-treated or control cells revealed a similar phosphopeptide pattern. Chemical cleavage with hydroxylamine and cyanogen bromide or digestion with trypsin and chymotrypsin localized the majority of receptor phosphorylation sites to a transactivation domain amino-terminal of the DNA-binding domain. Phosphorylation of this region, termed tau 1/enh2, was increased 2-3-fold by hormone treatment. The DNA-binding domain itself is weakly phosphorylated; no phosphorylation was found in the hormone-binding domain. Phosphorylated regions were also identified in receptor deletion mutants stably transfected into CV-1 monkey kidney cells. Hormone-independent phosphorylation was observed with a strong constitutively active mutant lacking the hormone-binding domain. No phosphorylation was detected in a mutant lacking the amino-terminal region, which showed only weak, hormone-dependent activity. These results support the idea that phosphorylation is important for the strength of the glucocorticoid receptor as a transcriptional regulator.


Urinary clearance of 113m In-DTPA and 99mTc-(Sn)DTPA measured by external arm counting.
Single shot glomerular filtration rate measurements involving chelates (113mIn-DTPA, 99mTc-DTPA etc) assume direct loss from the plasma to urine via glomerular filtration and excretion. Inherent errors, due to considerable uptake of activity in tissue and uncertainty of complete bladder emptying are ignored and taking of half-hourly blood and urine samples involves patient discomfort. This paper describes a simple method of measuring urinary clearance of chelates using serial external arm counting which entails only an initial injection and takes into account tissue loss from plasma. The resultant plotted curve exhibits three phases, the first two depicting input and equilibration between plasma and tissue and the third and exponential part, which is a measure of the biological half-life of the chelate, being representative of the efficiency of renal glomerular filtration, the parameter to be measured. Results obtained, compared with single shot glomerular filtration rate measurements performed simultaneously, gave better correlation with clinical data including renography.


Microfluidic interface technology based on stereolithography for glass-based lab-on-a-chips.
As lab-on-a-chips are developed for on-chip integrated microfluidic systems with multiple functions, the development of microfluidic interface (MFI) technology to enable integration of complex microfluidic systems becomes increasingly important and faces many technical difficulties. Such difficulties include the need for more complex structures, the possibility of biological or chemical cross-contamination between functional compartments, and the possible need for individual compartments fabricated from different substrate materials. This chapter introduces MFI technology, based on rapid stereolithography, for a glass-based miniaturized genetic sample preparation system, as an example of a complex lab-on-a-chip that could include functional elements such as; solid-phase DNA extraction, polymerase chain reaction, and capillary electrophoresis. To enable the integration of a complex lab-on-a-chip system in a single chip, MFI technology based on stereolithography provides a simple method for realizing complex arrangements of one-step plug-in microfluidic interconnects, integrated microvalves for microfluidic control, and optical windows for on-chip optical processes.


Involvement of α5 integrin in survivin-mediated osteosarcoma metastasis.
To investigate the role of survivin in osteosarcoma metastasis. Small interfering RNA (siRNA) was used to knockdown the expression of survivin and α5 integrin in the human osteosarcoma cell line MG63. Western blotting and immunostaining methods were used to assessed the effect of survivin knockdown on the expression of α5 integrin through flow cytometry and fluorescence microscopy detection. Meanwhile, the invasion and migration of transfected cells in Transwell and wound healing assays were probed, and the growth situation of these cells transplanted into nude mice was monitored. Knockdown of survivin expression could inhibit the invasion and migration of osteosarcoma MG64 cells in vitro and the expression of α5 integrin on osteosarcoma MG64 cell surface, suggesting that survivin can inhibit the invasion and migration of osteosarcoma cells through downregulation of α5 integrin. Anti-α5 integrin antibody could also markedly decrease the capability of invasion and migration of osteosarcoma MG64 cells. Additionally, knockdown of survivin expression could slow the growth of osteosarcoma MG63 cells transplanted into nude mice. Survivin-directed anti-tumor strategies might be an effective method in the treatment of osteosarcoma.


Introducing Clinical Informatics Course in Medical School Curricula: Lessons Learned from Medical Faculty University of Belgrade.
The healthcare environment in Serbia has changed dramatically over a last two decades, pointing out the necessity of clinical informatics (CI) education for future MDs. Total of 77 students were enrolled and 72 (93.5%) have successfully finished this course during 4 academic years. Mean total score for all students was 83.4 Âś 9.0 points, without difference between genders. We presented blended learning module as an effective way of gaining competences in CI and recommend this course to be required for future MDs.


Improved in situ saccharification of cellulose pretreated by dimethyl sulfoxide/ionic liquid using cellulase from a newly isolated Paenibacillus sp. LLZ1.
A cellulase producing strain was newly isolated from soil samples and identified as Paenibacillus sp. LLZ1. A novel aqueous-dimethyl sulfoxide (DMSO)/1-ethyl-3-methylimidazolium diethyl phosphate ([Emin]DEP)-cellulase system was designed and optimized. In the pretreatment, DMSO was found to be a low-cost substitute of up to 70% ionic liquid to enhance the cellulose dissolution. In the enzymatic saccharification, the optimum pH and temperature of the Paenibacillus sp. LLZ1 cellulase were identified as 6.0 and 40°C, respectively. Under the optimized reaction condition, the conversion of microcrystalline cellulose and bagasse cellulose increased by 39.3% and 37.6%, compared with unpretreated cellulose. Compared to current methods of saccharification, this new approach has several advantages including lower operating temperature, milder pH, and less usage of ionic liquid, indicating a marked progress in environmental friendly hydrolysis of biomass-based materials.


Popliteal Artery Entrapment Syndrome-Return to Sport Considerations: A Case Report.
This is a case of a 19-year-old female collegiate field hockey player with left leg pain, numbness, and tingling. A comprehensive workup including dynamic ultrasound, magnetic resonance imaging (MRI), and magnetic resonance angiogram (MRA) revealed a type VI functional popliteal artery entrapment syndrome (PAES). There are many options for treatment of functional PAES including activity modification, botulinum toxin injection, and surgery. To the authors' knowledge there is no published return to sport recommendation for postsurgical functional PAES. This report highlights alternative treatment options and proposes a postsurgical return to play rehabilitation protocol in functional PAES. LEVEL OF EVIDENCE: V.


The Prognostic Significance of PDE7B in Cytogenetically Normal Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) is a malignant hematological disease in which nearly half have normal cytogenetics. We have tried to find some significant molecular markers for this part of the cytogenetic normal AML, which hopes to provide a benefit for the diagnosis, molecular typing and prognosis prediction of AML patients. In the present study, we calculated and compared the gene expression profiles of cytogenetically normal acute myeloid leukemia (CN-AML) patients in database of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and dataset Vizome (a total of 632 CN-AML samples), and we have demonstrated a correlation between PDE7B gene and CN-AML. Then we proceeded to a survival analysis and prognostic risk analysis between the expression levels of PDE7B gene and CN-AML patients. The result showed that the event-free survival (EFS) and overall survival (OS) were significantly shorter in CN-AML patients with high PDE7B levels in each dataset. And we detected a significantly higher expression level of PDE7B in the leukemia stem cell (LSC) positive group. The Cox proportional hazards regression model showed that PDE7B is an independent risk predictor for CN-AML. All results indicate that PDE7B is an unfavorable prognostic factor for CN-AML.


Discordant Clostridioides difficile diagnostic assay and treatment practice: a cross-sectional study in a tertiary care hospital, Geneva, Switzerland.
To determine the proportion of patients who received a treatment for Clostridioides difficile infection (CDI) among those presenting a discordant C. difficile diagnostic assay and to identify patient characteristics associated with the decision to treat CDI. Cross-sectional study. Monocentric study in a tertiary care hospital, Geneva, Switzerland. Among 4562 adult patients tested for C. difficile between March 2017 and March 2019, 208 patients with discordant tests' results (positive nucleic acid amplification test (NAAT+)/negative enzyme immunoassay (EIA-)) were included. Treatment for CDI. CDI treatment was administered in 147 (71%) cases. In multivariate analysis, an abdominal CT scan with signs of colitis (OR 14.7; 95% CI 1.96 to 110.8) was the only factor associated with CDI treatment. The proportion of NAAT+/EIA- patients who received treatment questions the contribution of the EIA for the detection of toxin A/B after NAAT to limit overtreatment. Additional studies are needed to investigate if other factors are associated with the decision to treat.


Radical approaches to C-S bonds.
Organosulfur functionalities are ubiquitous in nature, pharmaceuticals, agrochemicals, materials and flavourants. Historically, these moieties were introduced almost exclusively using ionic chemistry; however, radical-based methods for the installation of sulfur-based functional groups have recently come to the fore. These radical methods have enabled their late-stage introduction into complex molecules, avoiding the need to preserve labile organosulfur moieties through multistep synthetic sequences. Here, we discuss homolytic C-S bond-forming processes, with a particular emphasis on radical substitution approaches to sulfide, disulfide and sulfinyl products, and the use of sulfur dioxide and its surrogates to build sulfonyl products. We also highlight the mechanistic considerations that we hope will guide further development of radical-based strategies compatible with the various organosulfur moieties that feature in modern chemistry.


TIMP Loss Activates Metalloproteinase-TNFα-DKK1 Axis To Compromise Wnt Signaling and Bone Mass.
Deregulated proteolysis invariably underlies most human diseases including bone pathologies. Metalloproteinases constitute the largest of the five protease families, and the metzincin metalloproteinases are inhibited by the four tissue inhibitors of metalloproteinase called TIMPs. We hypothesized that Timp genes are essential for skeletal homeostasis. We bred individual Timp knockout mice to generate unique mouse models, the quadruple Timp null strain (QT) as well as mice harboring only a single Timp3 allele (QT3+/- ). QT mice are grossly smaller and exhibit a dramatic reduction of trabeculae in long bones by μCT imaging with a corresponding increase in metalloproteinase activity. At the cellular level, Timp deficiency compromised differentiation markers, matrix deposition and mineralization in neonatal osteoblasts from calvariae, as well as the fibroblastic colony-forming unit (CFU-F) capacity of bone marrow-derived stromal cells. In contrast, we observed that osteoclasts were overactive in the Timp null state, consistent with the noted excessive bone resorption of QT bones. Immunohistochemistry (IHC) and immunofluorescence (IF) analyses of bone sections revealed higher Cathepsin K and RANKL signals upon Timp loss. Seeking the molecular mechanism, we identified abnormal TNFα bioactivity to be a central event in Timp-deficient mice. Specifically, TNFα triggered induction of the Wnt signaling inhibitor Dkk1 in the osteoblasts at the mRNA and protein levels, with a simultaneous increase in RANKL. Neutralizing TNFα antibody was capable of rescuing the induction of Dkk1 as well as RANKL. Therefore, the generation of novel Timp-deficient systems allowed us to uncover the essential and collective function of TIMP proteins in mammalian long-bone homeostasis. Moreover, our study discovers a functional TIMP/metalloproteinase-TNFα-Dkk1/RANKL nexus for optimal control of the bone microenvironment, which dictates coexistence of the osteoblast and osteoclast lineages. © 2018 American Society for Bone and Mineral Research.


Total knee arthroplasty in patients with extra-articular deformity.
Multiple acceptable options are available for the correction of distal femoral deformity associated with knee arthritis. The treatment modality should be chosen based on the extent of deformity and attention to preservation of the collateral ligaments. Surgical options range from osteotomy alone, arthroplasty with intra-articular correction, or arthroplasty with extra-articular correction. Different implant choices and fixation methods for the osteotomy possess advantages and disadvantages which need to be considered carefully. In addition to discussing principles of management based on current literature, this article includes a case report using a previously undescribed technique using corrective osteotomy, intramedullary nail fixation, and total knee arthroplasty with computer navigation.


Fibrillary glomerulonephritis without immunoglobulin deposits in the kidney.
Three patients are presented, who by electron microscopy, showed prominent fibrillary deposits in the glomeruli, and in two, also around the tubules. By immunohistology these two cases had no immunoglobulins in either glomeruli or around the tubules. In the third case, which probably represents a slightly different form of the disease, minor deposits of IgM were found in the glomeruli, while fibrillary deposits were extensive and widespread. It is suggested that precursors of fibrillary deposits may not be the same in all cases.


[The antitumor activities of gnidimacrin isolated from Stellera chamaejasme L].
Gnidimacrin, a diterpene compound, isolated from the methanol extract of Stellera chamaejasme L, showed significant antitumor activities against mouse leukemia P-388 and L-1210 in vivo. At the dosages of 0.02-0.03mg/kg ip, the in increase in life span (ILS) was 70% and 80%, respectively. Gnidimacrin was also active against murine solid tumors in vivo, such as Lewis lung carcinoma, B-16 melanoma and colon cancer 26. It showed ILSs of 40%, 49% and 41% at the dosages of 0.01-0.02mg/kg ip, respectively. Gnidimacrin strongly inhibited cell proliferation of human cancer cell lines such as leukemia K562, stomach cancers Kato-III, MKN-28, MKN-45, and mouse L-1210 by the MTT assay and colony forming assay in vitro. The IC50 of gnidimacrin was 0.007-0.00012microgram/ml. It is concluded that gnidimacrin is the principal antitumor element in Stellera chamaejasme L. with strong antitumor activities.


Emergency medical service aspects of emergency cardiac care.
Prehospital intervention has the potential for significantly affecting the outcome of cardiovascular emergencies. The authors examine multiple issues in prehospital care that can streamline and improve cardiac care. Improving access to prehospital care and increasing the use of the emergency medical services (EMS) system can speed interventions to the patients. The use of ECG in the out-of-hospital setting can reduce time to definitive treatment. Issues, such as the use of public access defibrillation and interfacility transports are also discussed.


Identification of binding sites for SR 46349B, a 5-hydroxytryptamine2 receptor antagonist, in rodent brain.
SR 46349B belongs to a new class of compounds (propenone oxime ether derivative) that inhibit 5-hydroxytryptamine (HT)2 receptors in vitro and in vivo. (3H) SR 46349B has been shown to bind with high affinity (Kd = 1.20 nM) to a single class of sites in rat prefrontal cortical membranes. The maximum binding capacity (Bmax = 0.262 pmol/mg of protein) is similar to that found for other classes of 5-HT2 receptor antagonists. Although the highest density of specific (3H) SR 46349B binding was found in cortex tissue, specific binding was also detectable in other brain areas. Among various receptor or channel ligands [including alpha or beta adrenergic, dopamine (D1 or D2), histamine (H1 or H2), 5-HT subclasses (5-HT1, 5-HT3), muscarinic and Na+ and Ca2+ channel blockers] only 5-HT2 receptor effectors were able to displace (3H) SR 46349B. In addition, the type of inhibition exerted by known 5-HT2 receptor antagonists such as ketanserin and ritanserin was investigated by saturation studies. In vivo, (3H) SR 46349B bound predominantly in mouse brain regions containing 5-HT2 receptors. This binding was displaced by SR 46349B, ketanserin and ritanserin following oral administration. From these results we suggest that SR 46349B in its tritiated form is a useful tool to label the 5-HT2 receptor in vitro and in vivo.


Effect of soman intoxication on the organization of rat brain ribosomes and the translational activity of mRNA in a cell-free system.
The effect of soman on rat brain ribosomes organization and translational activity of mRNA in cell-free system was studied in rats exposed to 1.3 LD50 soman (120 micrograms/kg body weight) and in rats repeatedly injected with 0.4 LD50 soman (35 micrograms/kg). Fifteen minutes after the injection of 1.3 LD50 soman the heavy polyribosomal fraction from rat brain was found to be enriched and translational activity of mRNA was enhanced. In rats administered five injections of 0.4 LD50 soman at 24-h intervals, the low density ribosomes appeared as the predominant fraction whereas the activity of mRNA in all cell-free system was significantly impaired. It is concluded that soman intoxication expresses a stimulatory or inhibitory effect on the processes of protein synthesis in the rat brain, depending on the dose schedule of soman administration.


Seroprevalence of influenza D virus in selected sample groups of Irish cattle, sheep and pigs.
Influenza D virus (IDV) is a new member of the Orthomyxoviridae family. It was first reported in swine in 2011 and isolated from bovine samples received for routine respiratory disease diagnosis in Ireland during 2014-2016. The goal of this study was to determine the seroprevalence in selected populations of IDV in cattle, pigs and sheep. Results showed a high prevalence of IDV in cattle sampled at slaughter (94.6%) or for diagnostic reasons (64.9%), whereas prevelance in samples taken for diagnostic reasons from sheep (4.5%) and pigs (5.8%) was much lower. This study suggests that IDV is widespread in Irish cattle.


Simultaneous determination of fluoroquinolones in foods of animal origin by a high performance liquid chromatography and a liquid chromatography tandem mass spectrometry with accelerated solvent extraction.
A confirmatory and quantitative method based on a high performance liquid chromatography UV detector (HPLC-UV) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) with an extraction procedure of accelerated solvent extraction (ASE) has been developed for simultaneous determination of 15 kinds of fluoroquinolones in various animal origin food samples. The sample preparation procedures consist of an extraction step with acetonitrile and a cleaning-up step with Oasis HLB cartridge. Parameters for extraction pressure and temperature, cycle of ASE, clean-up, and analysis procedure have been optimized systematically. The recoveries of FQNs spiked in the tissues as the muscle, liver, kidney of swine, bovine, chicken and fish at a concentration range of 10-800μg/kg were found between 70.6% and 111.1% with relative standard deviations (RSD) less than 15% in HPLC. The LOD and LOQ of the HPLC for the 15 FQNs were 3μg/kg and 10μg/kg, respectively, and those of the LC-MS/MS were 0.3 and 1μg/kg, respectively. These rapid and reliable methods can be used to efficiently separate, characterize and quantify the residues of 15 FQNs (Marbofloxacin, Enoxacin, Fleroxacin, Ofloxacin, Pefloxacin, Lomefloxacin, Danofloxacin, Enrofloxacin, Orbifloxacin, Cinoxacin, Gatifloxacin, Sarafloxacin, Difloxacin, Nalidixic Acid, Flumequine) in food of animal origin.


Persistence of anxiety symptoms after elective caesarean delivery.
In the UK, 11.8% of expectant mothers undergo an elective caesarean section (ELCS) representing 92 000 births per annum. It is not known to what extent this procedure has an impact on mental well-being in the longer term. To determine the prevalence and postpartum progression of anxiety and depression symptoms in women undergoing ELCS in Wales. Prevalence of depression and anxiety were determined in women at University Hospital Wales (2015-16; n = 308) through completion of the Edinburgh Postnatal Depression Scale (EPDS; ≥13) and State-Trait Anxiety Inventory (STAI; ≥40) questionnaires 1 day prior to ELCS, and three postpartum time points for 1 year. Maternal characteristics were determined from questionnaires and, where possible, confirmed from National Health Service maternity records. Using these criteria the prevalence of reported depression symptoms was 14.3% (95% CI 10.9-18.3) 1 day prior to ELCS, 8.0% (95% CI 4.2-12.5) within 1 week, 8.7% (95% CI 4.2-13.8) at 10 weeks and 12.4% (95% CI 6.4-18.4) 1 year postpartum. Prevalence of reported anxiety symptoms was 27.3% (95% CI 22.5-32.4), 21.7% (95% CI 15.8-28.0), 25.3% (95% CI 18.5-32.7) and 35.1% (95% CI 26.3-44.2) at these same stages. Prenatal anxiety was not resolved after ELCS more than 1 year after delivery. Women undergoing ELCS experience prolonged anxiety postpartum that merits focused clinical attention. None.


Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays.
The gastrointestinal tract (GIT), in particular, the small intestine, plays a significant role in food digestion, fluid and electrolyte transport, drug absorption and metabolism, and nutrient uptake. As the longest portion of the GIT, the small intestine also plays a vital role in protecting the host against pathogenic or opportunistic microbial invasion. However, establishing polarized intestinal tissue models in vitro that reflect the architecture and physiology of the gut has been a challenge for decades and the lack of translational models that predict human responses has impeded research in the drug absorption, metabolism, and drug-induced gastrointestinal toxicity space. Often, animals fail to recapitulate human physiology and do not predict human outcomes. Also, certain human pathogens are species specific and do not infect other hosts. Concerns such as variability of results, a low throughput format, and ethical considerations further complicate the use of animals for predicting the safety and efficacy xenobiotics in humans. These limitations necessitate the development of in vitro 3D human intestinal tissue models that recapitulate in vivo-like microenvironment and provide more physiologically relevant cellular responses so that they can better predict the safety and efficacy of pharmaceuticals and toxicants. Over the past decade, much progress has been made in the development of in vitro intestinal models (organoids and 3D-organotypic tissues) using either inducible pluripotent or adult stem cells. Among the models, the MatTek's intestinal tissue model (EpiIntestinal™ Ashland, MA) has been used extensively by the pharmaceutical industry to study drug permeation, metabolism, drug-induced GI toxicity, pathogen infections, inflammation, wound healing, and as a predictive model for a clinical adverse outcome (diarrhea) to pharmaceutical drugs. In this paper, our review will focus on the potential of in vitro small intestinal tissues as preclinical research tool and as alternative to the use of animals.


A composite model of survival from out-of-hospital cardiac arrest using the Cardiac Arrest Registry to Enhance Survival (CARES).
Using CARES data, to develop a composite multivariate logistic regression model of survival for projecting survival rates for out-of-hospital arrests of presumed cardiac etiology (OHCA). This is an analysis of 25,975 OHCA cases (from October 1, 2005 to December 31, 2011) occurring before EMS/first responder arrival and involving attempted resuscitation by responders from 125 EMS agencies. The survival-at-hospital discharge rate was 9% for all cases, 16% for bystander-witnessed cases, 4% for unwitnessed cases, and 32% for bystander-witnessed pVT/VF cases. The model was estimated separately for each set of cases above. Generally, our first equation showed that joint presence of a presenting rhythm of pVT/VF and return of spontaneous circulation in the pre-hospital setting (PREHOSPROSC) is a substantial direct predictor of patient survival (e.g., 55% of such cases survived). Bystander AED use, and, for witnessed cases, bystander CPR and response time are significant but less sizable direct predictors of survival. Our second equation shows that these variables make an additional, indirect contribution to survival by affecting the probability of joint presence of pVT/VF and PREHOSPROSC. The model yields survival rate projections for various improvement scenarios; for example, if all cases had involved bystander AED use (vs. 4% currently), the survival rate would have increased to 14%. Approximately one-half of projected increases come from indirect effects that would have been missed by the conventional single-equation approach. The composite model describes major connections among predictors of survival, and yields specific projections for consideration when allocating scarce resources to impact OHCA survival.


Nutritional problems of the acute and chronic burn patient. Relevance to epidermolysis bullosa.
The hemodynamic response and metabolic needs of the burn patient may provide insights into the changes occurring in patients with epidermolysis bullosa as well as into potential therapeutic interventions.


Early and repetitive stimulation of the arm can substantially improve the long-term outcome after stroke: a 5-year follow-up study of a randomized trial.
Several studies have investigated the effect of therapeutic interventions for the arm in the acute phase after stroke, with follow-ups at a maximum of 12 months. The aim of this study was to examine the effect of repetitive sensorimotor training of the arm at 5 years after stroke. One hundred consecutive stroke patients were randomly allocated either to an experimental group that received daily additional sensorimotor stimulation of the arm or to a control group. The intervention period was 6 weeks. Assessments of the patients were made before, midway, and after intervention, and at 6 and 12 months after stroke. In this study, 62 patients were reassessed at 5 years after stroke. The Brunnström-Fugl-Meyer (BFM) test, Action Research Arm (ARA) test, and Barthel index (BI) were used as the primary outcome measures. At the 5-year follow-up, there was a statistically significant difference for both the BFM and ARA tests in favor of the experimental group. The mean differences in improvement between the groups from the initial evaluation to the 5-year assessment corresponded to 17 points on the BFM and 17.4 on the ARA. No effect was found for the BI. The treatment was most effective in patients with a severe initial motor deficit. Adding a specific intervention for the arm during the acute phase after a stroke resulted in a clinically meaningful and long-lasting effect on motor function. The effect can be attributed to early, repetitive, and targeted stimulation.


Crystallization and properties of L-arginine deiminase of Pseudomonas putida.
Crystalline L-arginine deiminase of Pseudomonas putida was prepared by the following steps: sonic disruption, ammonium sulfate fractionation, protamine sulfate treatment, DEAE-cellulose column chromatography, and L-arginine-Sepharose 6B chromatography followed by crystallization. This procedure yields a crystalline pure enzyme with a 45% recovery of the activity in crude cell-free extracts. The yield is significantly higher than that reported for this enzyme. The purified enzyme appears to be homogeneous in ultracentrifugation (s-o20, w equals 10.2 S) and isoelectric focusing (pI equals 6.13). The purified enzyme showed two bands on disc gel electrophoresis, both carrying out the deimination of L-arginine. Electrophoresis in the presence of beta-mercaptoethanol plus Na dodecyl-SO4 gave a single band (Mr, 54,000). Specific activity of this enzyme was 58.8 mumol of L-citrulline formed per min per mg of protein at 37 degrees. The optimum pH of the purified enzyme was 6.0 and maximal activity was obtained at 50 degrees. The molecular weight of the native protein was 130,000 by gel filtration and 120,000 by sedimentation-equilibrium measurements. The spectrum of the pure enzyme showed absorption maximum at 280 nm and the value of E-1%-1 CM AT 280 NM WAS 10.48 IN 0.05 M potassium phosphate buffer (pH 7.0). The crystalline enzyme hydrolyzed several L-arginine analogues. L-Homoarginine, L-alpha-amino-gamma-guanidinobutyric acid, and L-alpha-amino-beta-guanidinopropionic acid competitively inhibited the hydrolysis of L-arginine with Ki values of 25.7, 7.5, and 4.0 times 10- minus 3 M, respectively. p-Chloromercuribenzoate, Ag-+, and Hg-2+, and several metal ions inhibited the enzyme.


Peroxymonosulfate activation by Co3O4/SnO2 for efficient degradation of ofloxacin under visible light.
In this work, Co3O4/SnO2 catalyst was prepared by a one-pot hydrothermal method and applied in the activation of peroxymonosulfate (PMS) for the degradation of the target pollutant ofloxacin (OFX). The results showed that the PMS/Co3O4/SnO2-8% system had a 92% OFX degradation efficiency after 30 min of catalytic reaction, which was 46 times higher than that of PMS/SnO2 alone, and the degradation efficiency could be maintained in a wide pH range (5-11). In addition, reactive oxygen species quenching experiments and electron spin resonance spectra confirmed that sulfate radicals, superoxide radicals, hydroxyl radicals and singlet oxygen were the dominant active groups. The excellent recyclability and stability of the as-prepared catalyst were confirmed by cycling experiments and characterization results. Finally, a possible degradation pathway of OFX was suggested, and the intermediate toxicity of this system was identified and analyzed by a quantitative structure-activity relationship (QSAR).


Radioresistant pseudo-colony formation in the PHA-leukocyte feeder colony assay.
In the PHA-leukocyte feeder colony assay--a fluid assay on top of an agar underlayer--colonies might not be the product of clonogenic cells but rather from aggregates, as was already shown for hairy cell leukemia (Leukemia Res. 11, 911 (1987)). To study the role of aggregation in this colony assay in other B-cell malignancies, we irradiated cells from B-chronic lymphocytic leukemia, B-non-Hodgkin's lymphoma and multiple myeloma. In nearly all cases, viable "colonies" were seen after irradiation, albeit in lower numbers. These data indicate that in the PHA-leukocyte feeder colony assay, a considerable percentage of colonies from a large variety of B-cell malignancies originate from aggregating rather than from proliferating cells.


Strength or power, which is more important to prevent slip-related falls?
Falls are a serious health and medical concern facing older adults worldwide. Both muscle strength and power have been related to falls among older adults. The primary purpose of this study was to identify which one of these two muscular performances is more important in preventing a slip-related fall. Twenty-six healthy young adults participated in this study. Their muscle strength (torque) and power capacities were assessed at the right knee under maximum voluntary isometric (flexion and extension) and isokinetic (concentric extension and flexion at three different contraction speeds: 60 deg/s, 120 deg/s, and 180 deg/s) contractions, respectively. They were then subjected to an identical and unannounced slip during gait on a treadmill under the protection of a safety harness after walking regularly for five times on the treadmill. Accuracy of predicting slip outcome (fall vs. recovery) was examined for each muscle performance measurement using logistic regression. Results showed that overall the joint power capacity measurements predicted the slip outcome among these subjects with higher accuracy than did the joint torque capacity measurements. Such results suggested that muscle power could be more closely related to a fall initiated by a slip during gait. The findings from the present study could provide guidance to identify individuals at increased risk of falling using the joint power capacity measurement and to design effective fall prevention training paradigms aiming at maximizing muscle power among older adults and others with physical disabilities.


Long-term consequences of severe health anxiety on sick leave in treated and untreated patients: Analysis alongside a randomised controlled trial.
Health anxiety (HA) is prevalent and costly for health services. However, little is known about the full societal burden of HA. Based on complete register data, we (1) compared weeks on sickness-related benefits (SB) in untreated patients with severe HA (n=126) with a matched population sample (n=12,600); and (2) tested whether Acceptance & Commitment group Therapy (ACT-G) (n=63) reduced weeks on SB during the first year after randomisation compared to a waitlist (n=63). We found that (1) HA patients showed a six-monthly increment of 2 weeks on SB compared with the general population (p<0.0001), and (2) that ACT-G and the waitlist showed no difference in their ability to reduce SB during the first year (p=0.246). We conclude that HA is associated with a considerable societal burden. A possible beneficial effect of psychotherapy on SB needs further investigation.


Medication utilization pattern among outpatients during the Hajj mass gathering.
The Kingdom of Saudi Arabia (KSA) provides free healthcare, including medications, for the over 2 million Muslim pilgrims who attend Hajj every year. Information on drug utilization patterns at the Hajj is important to strengthen the supply chain for medicines, avert stock-outs, identify inappropriate use, and support public health planning for the event. We investigated drug utilization pattern among outpatients in eight seasonal Holy sites hospitals in Makkah, KSA, during the 2018 Hajj. Data on medication prescribed and dispensed were retrieved from the hospitals' electronic records. Data were also used to calculate six of the WHO indicators for drug use at these facilities. A total of 99,117 medications were prescribed for 37,367 outpatients during 37,933 encounters. Outpatients were mainly older males and originated from 134 countries. Twenty medications accounted for 72.8% of the 323 different medications prescribed. These were mainly nonsteroidal anti-inflammatory drugs, analgesics and antipyretics, and antibacterial medicines for systemic use. Outpatients were prescribed an average of 2.6 (SD = 1.2) drugs per consultation and polypharmacy (≥5 medications) was observed in 4.8% of the encounters. Antibiotics and an injection were prescribed in 46.9% and 6.5% of encounters, respectively. Nearly 90% of the prescribed drugs were actually dispensed. On average, medications were dispensed 16.4 (SD = 119.8) minutes from the time they were prescribed for the patient. All hospitals had a copy of the essential drugs list available and all of the prescribed drugs appeared on that list. Nonsteroidal anti-inflammatory drugs, analgesics and antibiotics are the most common medications prescribed to outpatient during Hajj. Our results, including the calculated WHO drug use indicators, can form a basis for further investigations into appropriate drug use at the Hajj and for planning purposes. These results could also guide the development of reference values for medications prescribing and use indicators at mass gatherings.


Efficient production and purification of extracellular domain of human FGFR-Fc fusion proteins from Chinese hamster ovary cells.
The family of fibroblast growth factor receptors (FGFRs) plays an important role in cell growth, survival, differentiation and angiogenesis. The three immunoglobulin-like extracellular domains of FGFR (D1, D2, and D3) are critical for ligand binding and specificity towards fibroblast growth factor and heparan sulfate. Fibroblast growth factor receptors are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for different types of anticancer therapies. In this study, we have cloned, expressed in CHO cells and purified Fc-fused extracellular domains of different types of FGFRs (ECD_FGFR1a-Fc, ECD_FGFR1b-Fc, ECD_FGFR2a-Fc, ECD_FGFR2b-Fc, ECD_FGFR3a-Fc, ECD_FGFR3b-Fc, ECD_FGFR4a-Fc, ECD_FGFR4b-Fc), which could be used as molecular targets for the selection of specific antibodies. The fusion proteins were analyzed using gel electrophoresis, Western blotting and mass spectrometry. To facilitate their full characterization, the fusion proteins were deglycosylated using PNGase F enzyme. With an optimized transient transfection protocol and purification procedure we were able to express the proteins at a high level and purify them to homogeneity.