Optimal management strategy for incidental findings in trauma patients: an initiative for midlevel providers.
Increasing patient volume and residents' work hour restrictions have increased the workload at trauma centers. Further, comprehensive tertiary surveys after initial stabilization and appropriate follow-up plans for incidental findings are time consuming. Midlevel providers (MLP) can help streamline this process. We initiated a care plan in which MLPs conducted all tertiary surveys and coordinated follow-ups for incidental findings. From November 2005 through May 2006, we implemented a MLP-driven initiative aimed at performing tertiary surveys within 48 hours of admission on all trauma patients admitted to our Level-1 trauma center. Tertiary surveys consisted of a complete history and physical, radiographic evaluations and appropriate consultations. Incidental findings were recorded and communicated to the trauma attending. A follow-up plan was devised, and the course of action was documented. Patients or family members were informed, and their acknowledgments were filed. Data are presented as mean +/- SE. There were 1,027 patients admitted during the study period. Blunt mechanisms accounted for 81% of the injuries (primarily motor vehicle crashes and falls). Seventy-six patients had 87 incidental findings (7.4%); 53 were men. The mean age was 51.8 years +/- 2.1 years and mean injury severity score was 18.5 +/- 1.4. Incidental findings of clinical significance included 18 pulmonary nodules or neoplasms, 9 adrenal masses (>4 mm), 7 patients with lymphadenopathy, 5 benign cystic lesions, and 3 renal masses. Other neoplastic lesions included bladder (2), thyroid (2), ovary (1), breast (1), and rectum (1). With prevalent medicolegal pressure and restricted residents' work hours, a MLP-initiative to streamline the tertiary survey effectively addresses incidental findings. This MLP-driven care plan can help reduce residents' workload, provides appropriate follow-up, and minimizes legal risks inherent to incidental findings on the trauma service.


In-plane photonic transduction of silicon-on-insulator microcantilevers.
We demonstrate an in-plane photonic transduction method for microcantilevers, which have been widely investigated for sensor applications. In our approach the microcantilever is etched to form a single mode rib waveguide. Light propagates down the microcantilever and crosses a small gap at the free end of the microcantilever, some of which is captured by an asymmetrical multimode waveguide that terminates in a Y-branch. The Y-branch outputs are used to form a differential signal that is monotonically dependent on microcantilever deflection. The measured differential signal matches simulation when microcantilever rotation is properly accounted for. The measured differential signal sensitivity is 1.4 x 10(-4) nm(-1) and the minimum detectable deflection is 0.35 nm.


Toward a patient-specific tissue engineered vascular graft.
Integrating three-dimensional printing with the creation of tissue-engineered vascular grafts could provide a readily available, patient-specific, autologous tissue source that could significantly improve outcomes in newborns with congenital heart disease. Here, we present the recent case of a candidate for our tissue-engineered vascular graft clinical trial deemed ineligible due to complex anatomical requirements and consider the application of three-dimensional printing technologies for a patient-specific graft. We 3D-printed a closed-disposable seeding device and validated that it performed equivalently to the traditional open seeding technique using ovine bone marrow-derived mononuclear cells. Next, our candidate's preoperative imaging was reviewed to propose a patient-specific graft. A seeding apparatus was then designed to accommodate the custom graft and 3D-printed on a commodity fused deposition modeler. This exploratory feasibility study represents an important proof of concept advancing progress toward a rationally designed patient-specific tissue-engineered vascular graft for clinical application.


Study of Siphon Breaker Experiment and Simulation for a Research Reactor.
Under the design conditions of a research reactor, the siphon phenomenon induced by pipe rupture can cause continuous outward flow of water. To prevent this outflow, a control device is required. A siphon breaker is a type of safety device that can be utilized to control the loss of coolant water effectively. To analyze the characteristics of siphon breaking, a real-scale experiment was conducted. From the results of the experiment, it was found that there are several design factors that affect the siphon breaking phenomenon. Therefore, there is a need to develop a theoretical model capable of predicting and analyzing the siphon breaking phenomenon under various design conditions. Using the experimental data, it was possible to formulate a theoretical model that accurately predicts the progress and the result of the siphon breaking phenomenon. The established theoretical model is based on fluid mechanics and incorporates the Chisholm model to analyze two-phase flow. From Bernoulli's equation, the velocity, quantity, undershooting height, water level, pressure, friction coefficient, and factors related to the two-phase flow could be obtained or calculated. Moreover, to utilize the model established in this study, a siphon breaker analysis and design program was developed. The simulation program operates on the theoretical model basis and returns the result as a graph. The user can confirm the possibility of the siphon breaking by checking the shape of the graph. Furthermore, saving the entire simulation result is possible and it can be used as a resource for analyzing the real siphon breaking system. In conclusion, the user can confirm the status of the siphon breaking and design the siphon breaker system using the program developed in this study.


Quantification of Bacterial DNA from Infected Human Root Canals Using qPCR and DAPI after Disinfection with Established and Novel Irrigation Protocols.
The removal of bacterial infections within the root canal system is still a challenge. Therefore, the cleansing effect of established and new irrigation-protocols (IP) containing silver diamine fluoride (SDF) 3.8% on the whole root canal system was analyzed using quantitative PCR (qPCR) and 4',6-diamidino-phenylindole-(DAPI)-staining. Extracted human premolars were instrumented up to F2 (ProTaper Gold) under NaCl 0.9% irrigation and incubated with Enterococcus faecalis for 42 days. Subsequently, different ultrasonically agitated IP were applied to the roots: control (no irrigation), 1. NaOCl 3%, EDTA 20%, CHX 2%, 2. NaOCl 3%, EDTA 20%, 3. NaOCl 3%, EDTA 20%, SDF 3.8%, 4. SDF 3.8%, and 5. NaCl 0.9%. One half of the root was investigated fluorescent-microscopically with DAPI. The other half was grinded in a cryogenic mill and the bacterial DNA was quantified with qPCR. The qPCR results showed a statistically significant reduction of bacteria after the application of IP 1, 2, and 3 compared to the control group. While IP 4 lead to a bacterial reduction which was not significant, IP 5 showed no reduction. These data corresponded with DAPI staining. With qPCR a new molecular-biological method for the investigation of the complete root canal system was implemented. The novel IP 3 had an equally good cleansing effect as the already established IP.


Intraoperative Hypotension and Acute Kidney Injury in Non-cardiac Surgery at a Large Tertiary Care Medical Center.
Acute kidney injury (AKI) is a serious postoperative complication that increases patients' risk for long- and shortterm morbidity and mortality. Risk for developing AKI increases following intraoperative hypotension (IOH). This project aimed to describe the rate of and establish IOH as an independent risk factor for AKI among adults undergoing non-cardiac surgery at a large tertiary care medical center. An observational, retrospective, evidence-based practice project was conducted. Records were extracted for adults undergoing general anesthesia for non-cardiac surgery from 2015 to 2019 with available serum creatinine laboratory results. The primary project outcome was postoperative AKI. Among 4,603 cases, 8.9% experienced postoperative AKI. Cases with IOH (MAPs less than 60 mmHg for at least 10 minutes) compared to cases without IOH had increased risks for AKI (RR 1.48, 95% CI [1.19-1.84], P<.001). In a fully adjusted model, IOH was an independent risk factor for AKI (OR 1.50, 95% CI [1.18-1.92], P=.001). Among cases with serum creatinine laboratory results, the rate of AKI was higher than reported literature rates. IOH was confirmed as an independent risk factor. Quantifying the rate of and risk factors for AKI may precipitate heightened attention to prevention strategies and encourage quality improvement initiatives.


Non-Stationary Complementary Non-Uniform Sampling (NOSCO NUS) for Fast Acquisition of Serial 2D NMR Titration Data.
NMR spectroscopy offers unique benefits for ligand binding studies on isotopically labelled target proteins. These benefits include atomic resolution, direct distinction of binding sites and modes, a lowest detectable affinity limit, and function independent setup. Yet, retracing protein signal assignments from apo to holo states to derive exact dissociation constants and chemical shift perturbation amplitudes (for ligand docking and structure-based optimization) requires lengthy titration series of 2D heteronuclear correlation spectra at variable ligand concentration that may exceed the protein's lifetime and available spectrometer time. We present a novel method to overcome this critical limitation, based on non-stationary complementary non-uniform sampling (NOSCO NUS) combined with a robust particle swarm optimization algorithm. We illustrate its potential in two challenging studies with very distinct protein sizes and binding affinities, showing that NOSCO NUS can reduce measurement times by an order of magnitude to make such highly informative NMR titration studies more broadly feasible.


Serum interleukin-18 concentrations in patients with inflammatory bowel disease.
Elevated expression of interleukin (IL)-18 mRNA and protein in intestinal mucosa, attributable to activated monocytes and macrophages in that site, has been reported in patients with inflammatory bowel disease (IBD). However, changes in serum IL-18 concentrations in patients with IBD have not been reported. We measured bioactive IL-18 in serum from patients with IBD, using an enzyme-linked immunosorbent assay (ELISA). Mean serum IL-18 concentrations in 5 patients with Crohn disease (CD) were 400 pg/mL, approximately 1.7 times higher than concentrations in 21 control subjects (p < 0.01). However, serum IL-18 was not increased in patients with ulcerative colitis (UC). These results suggest that like other T-helper type 1 (Th1) cytokines IL-18 may play a key pathogenetic role in Th1-mediated disorders, such as CD. Regulation and expression of IL-18 appears to differ between CD and UC, and serum IL-18 may be a useful clinical marker for CD.


ROLE OF BONE GRAFTS AND BONE GRAFT SUBSTITUTES IN ISOLATED SUBTALAR JOINT ARTHRODESIS.
The purpose of this study was to compare union rates for isolated subtalar arthrodesis with and without the use of bone grafts or bone graft substitutes. We retrospectively reviewed 135 subtalar fusions with a mean follow-up of 18 ± 14 months. The standard approach was used for all surgeries. Graft materials included b-tricalcium phosphate, demineralized bone matrix, iliac crest autograft and allograft, and allograft cancellous chips. Successful subtalar fusion was determined clinically and radiographically. There was an 88% (37/42) union rate without graft use and an 83% (78/93) union rate with bone graft use. Odds ratio of union for graft versus no graft was 0.703 (95% CI, 0.237-2.08). The average time to union in the graft group was 3 ± 0.73 months and 3 ± 0.86 in the non-graft group, with no statistically significant difference detected (p = 0.56). Graft use did not improve union rates for subtalar arthrodesis. Level of Evidence IV, Case Series.


Dynamic maximum entropy provides accurate approximation of structured population dynamics.
Realistic models of biological processes typically involve interacting components on multiple scales, driven by changing environment and inherent stochasticity. Such models are often analytically and numerically intractable. We revisit a dynamic maximum entropy method that combines a static maximum entropy with a quasi-stationary approximation. This allows us to reduce stochastic non-equilibrium dynamics expressed by the Fokker-Planck equation to a simpler low-dimensional deterministic dynamics, without the need to track microscopic details. Although the method has been previously applied to a few (rather complicated) applications in population genetics, our main goal here is to explain and to better understand how the method works. We demonstrate the usefulness of the method for two widely studied stochastic problems, highlighting its accuracy in capturing important macroscopic quantities even in rapidly changing non-stationary conditions. For the Ornstein-Uhlenbeck process, the method recovers the exact dynamics whilst for a stochastic island model with migration from other habitats, the approximation retains high macroscopic accuracy under a wide range of scenarios in a dynamic environment.


Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells.
The elongation competence of the RNA polymerase II complex is critically dependent on the positive transcription elongation factor b (P-TEFb). P-TEFb exists in two forms in cells, an active form composed of cyclin T1 and CDK9 and an inactive form, in which cyclin T1/CDK9 is sequestered by Hexim1 and 7SK snRNA. Here, we report that partitioning of active and inactive P-TEFb is regulated by acetylation of cyclin T1. Cyclin T1 acetylation triggers dissociation of Hexim1 and 7SK snRNA from cyclin T1/CDK9 and activates the transcriptional activity of P-TEFb. This activation is lost in P-TEFb complexes containing cyclin T1 that can no longer be acetylated. An acetylation-deficient cyclin T1 mutant dominantly suppresses NF-kappaB-mediated activation of the interleukin-8 promoter but continues to synergize normally with the HIV Tat protein to transactivate the HIV long terminal repeat. These findings support the model that acetylation of cyclin T1 serves as a physiological switch that liberates P-TEFb from its endogenous inhibitors Hexim1 and 7SK snRNA, but is not required for the cooperative action with HIV Tat.


Effects of purified fibronectin alone and combined with immunoglobulin G or antithrombin-III on survival during gram-negative peritonitis or endotoxemia in rats.
The present study was performed to determine the effects of pretreatment with purified human plasma fibronectin (FN) on survival in rats challenged with Salmonella typhimurium peritonitis or E. coli endotoxemia. The effects on survival of combining FN with immunoglobulin G (IgG) or antithrombin-III (AT-III) were also determined during S. typhimurium peritonitis and E. coli endotoxemia. Permanent survival was increased 15% in the peritonitis group (p less than 0.05) and 15% in the endotoxemic group (p greater than 0.05). There was no enhancement in survival by combining FN with a subprotective dose of IgG preparation. AT-III alone increased survival by 50% over survival in the control group. Combining FN with AT-III increased survival 10% greater than with AT-III alone, which is suggestive of an additive effect. Results from this study suggest that FN provides modest protection during Gram-negative peritonitis or endotoxemia in the rat. Combining FN with AT-III may augment in an additive manner the marked increase in survival observed with AT-III alone in this and previous studies.


The heme-responsive element of the mouse heme oxygenase-1 gene is an extended AP-1 binding site that resembles the recognition sequences for MAF and NF-E2 transcription factors.
Jun and Fos (AP-1) transcription factors were recently proposed to mediate induction of the mouse heme oxygenase-1 gene by different agents including heme and cadmium. In this report we show that the AP-1 binding sequence, TGAGTCA, is necessary but insufficient for gene activation in response to heme or cadmium. The minimal heme response element was identified as an extended AP-1 binding site, (T/C)GCTGAGTCA. In addition to the AP-1 heptad, this element also contains an interdigitated antioxidant response element, GCnnnGTCA. Specific antioxidant response elements from the NAD(P)H:quinone oxidoreductase-1 and the glutathione S-transferase Ya subunit genes were in fact responsive to heme but not all sequences that conform to the consensus antioxidant response element were activated by this agent. The heme response element resembles the consensus binding sites for the product of the maf oncogene and for the transcription factor NF-E2. The potential role of these and related transcription factors and the implication of the composite heme response element in heme oxygenase-1 gene regulation are discussed.


A Review of Hologram Storage and Self-Written Waveguides Formation in Photopolymer Media.
Photopolymer materials have received a great deal of attention because they are inexpensive, self-processing materials that are extremely versatile, offering many advantages over more traditional materials. To achieve their full potential, there is significant value in understanding the photophysical and photochemical processes taking place within such materials. This paper includes a brief review of recent attempts to more fully understand what is needed to optimize the performance of photopolymer materials for Holographic Data Storage (HDS) and Self-Written Waveguides (SWWs) applications. Specifically, we aim to discuss the evolution of our understanding of what takes place inside these materials and what happens during photopolymerization process, with the objective of further improving the performance of such materials. Starting with a review of the photosensitizer absorptivity, a dye model combining the associated electromagnetics and photochemical kinetics is presented. Thereafter, the optimization of photopolymer materials for HDS and SWWs applications is reviewed. It is clear that many promising materials are being developed for the next generation optical applications media.


Evaluation of mRNA expression of human drug-metabolizing enzymes and transporters in chimeric mouse with humanized liver.
The hepatic mRNA expression of human drug-metabolizing enzymes and transporters in chimeric mise with almost-completely humanized liver (replacement index: 71-89%) was investigated. The mRNAs of 58 human phase I enzymes, 26 human phase II enzymes, 23 human transporters, and five mouse Cyps were measured in the chimeric mice with humanized liver generated using hepatocytes from a Japanese donor. The mRNA expression of 52 human phase I enzymes, which includes 20 human CYPs, 26 human phase II enzymes and 21 human transporters was ascertained in the chimeric mouse liver. Among them, the expression of the target mRNAs vital for liver function such as the metabolism and secretion of endogenous compounds appeared to be maintained. The central value for the expression ratio in all target genes in chimeric mouse liver to the donor liver was 0.46, which was lower than the substitution rate of chimeric mouse liver by donor liver. The ratio of mouse Cyp mRNA expression of chimeric mouse liver to that of control mouse liver was 0.19 or less, except for that of Cyp2b10. There were good correlations between the mRNA expression levels of human hepatic albumin gene, the values of the rate of replacement of mouse liver by human liver, and the human blood albumin concentration in the chimeric mice. The chimeric mice with humanized liver may be a useful tool for the evaluation of drug-drug interactions such as the inhibition and induction of drug-metabolizing enzymes and transporters.


Design and Manufacture of a Low-Cost Microfluidic System for the Synthesis of Giant Liposomes for the Encapsulation of Yeast Homologues: Applications in the Screening of Membrane-Active Peptide Libraries.
The discovery of new membrane-active peptides (MAPs) is an area of considerable interest in modern biotechnology considering their ample applicability in several fields ranging from the development of novel delivery vehicles (via cell-penetrating peptides) to responding to the latent threat of antibiotic resistance (via antimicrobial peptides). Different strategies have been devised for such discovery process, however, most of them involve costly, tedious, and low-efficiency methods. We have recently proposed an alternative route based on constructing a non-rationally designed library recombinantly expressed on the yeasts' surfaces. However, a major challenge is to conduct a robust and high-throughput screening of possible candidates with membrane activity. Here, we addressed this issue by putting forward low-cost microfluidic platforms for both the synthesis of Giant Unilamellar Vesicles (GUVs) as mimicking entities of cell membranes and for providing intimate contact between GUVs and homologues of yeasts expressing MAPs. The homologues were chitosan microparticles functionalized with the membrane translocating peptide Buforin II, while intimate contact was through passive micromixers with different channel geometries. Both microfluidic platforms were evaluated both in silico (via Multiphysics simulations) and in vitro with a high agreement between the two approaches. Large and stable GUVs (5-100 µm) were synthesized effectively, and the mixing processes were comprehensively studied leading to finding the best operating parameters. A serpentine micromixer equipped with circular features showed the highest average encapsulation efficiencies, which was explained by the unique mixing patterns achieved within the device. The microfluidic devices developed here demonstrate high potential as platforms for the discovery of novel MAPs as well as for other applications in the biomedical field such as the encapsulation and controlled delivery of bioactive compounds.


The cryoprotective effects of vitamin B12 supplementation on bovine semen quality.
The present study aimed to investigate the effects of vitamin B(12) supplementation on standard bovine semen quality parameters and anti-oxidative enzyme activities. Vitamin B(12) was supplemented at concentrations of 1.25, 2.5, 3.75 and 5.0 mg/ml to bovine semen cryoprotective medium. The results indicated that the motility and straight line velocity, curvilinear velocity, mean coefficient, velocity of the average path values of sperm supplemented with 2.50 mg/ml vitamin B(12) were significantly higher than that of other groups (p<0.05). No significant difference was observed for linearity index, lateral head displacement values and the percentage of grade A spermatozoa between the extenders containing 2.50 and 3.75 mg/ml vitamin B(12) (p>0.05). The percentages of acrosome-intact and plasma membrane-intact spermatozoa were significantly improved (p<0.05) by supplementing with 2.50 mg/ml vitamin B(12) . The results of biochemical assay revealed that vitamin B(12) supplementation did not cause significant changes in superoxide dismutase levels compared with control (p>0.05). However, the catalase levels were higher in the treatment supplemented with vitamin B(12) at 2.50 mg/ml, when compared with other groups (p<0.05). The extender supplemented with vitamin B(12) significantly decreased glutathione peroxidase activity compared with the control (p<0.05). The supplementation of 3.75 mg/ml vitamin B(12) caused the highest value of glutathione reductase activity, compared with other groups (p<0.05). In conclusion, the extender supplemented with vitamin B(12) could reduce the oxidative stress provoked by freezing-thawing and improve bovine semen quality. Further studies are required to obtain more concrete results on the determination of lipid peroxidation and antioxidant capacities of vitamin B(12) in cryopreserved bovine semen.


Tissue polarity points from cells that have higher Frizzled levels towards cells that have lower Frizzled levels.
The frizzled (fz) gene of Drosophila encodes the founding member of the large family of receptors for the Wnt family of signaling molecules. It was originally studied in the adult epidermis, where it plays a key role in the generation of tissue polarity. Mutations in components of the fz signal transduction pathway disrupt tissue polarity; on the wing, hairs normally point distally but their polarity is altered by these mutations. We devised a method to induce a gradient of fz expression with the highest levels near the distal wing tip. The result was a large area of proximally pointing hairs in this region. This reversal of polarity was seen when fz expression was induced just before the start of hair morphogenesis when polarity is established, suggesting that the gradient of Fz protein acted fairly directly to reverse hair polarity. A similar induction of the dishevelled (dsh) gene, which acts cell autonomously and functions downstream of fz in the generation of tissue polarity, resulted in a distinct tissue polarity phenotype, but no reversal of polarity; this argues that fz signaling was required for polarity reversal. Furthermore, the finding that functional dsh was required for the reversal of polarity argues that the reversal requires normal fz signal transduction. The data suggest that cells sense the level of Fz protein on neighboring cells and use this information in order to polarize themselves. A polarizing signal is transmitted from cells with higher Fz levels to cells with lower levels. Our observations enable us to propose a general mechanism to explain how Wnts polarize target cells.


Marked efficacy of adalimumab for secondary gastrointestinal amyloidosis accompanied with ankylosing spondylitis.
A 39-year-old man with seronegative rheumatoid arthritis which was refractory to methotrexate and prednisolone therapy complained of epigastralgia, melena and diarrhea. Diffuse mucosal damage was observed on endoscopic examination, and histological findings of the gastric and colonal mucosa showed AA type amyloidosis. He was diagnosed with ankylosing spondylitis (AS) on the basis of the clinical feature such as the limitation in range of motion of lumber spine, and sacroiliitis on MR imaging. Although digestive symptom ameliorated by fasting and antibiotic therapy, laboratory findings continued to reveal an elevation of serum C-reactive protein (CRP) value and arthritis worsened. However, after the initiation of the treatment with adalimumab (ADA), not only his manifestation but also serum levels of CRP became normalized promptly. As far as we could evaluated, follow-up colonoscopic examination showed normal mucosal findings and histologic examination proved that amyloid protein disappeared. Secondary gastrointestinal amyloidosis is ralely associated with AS. Therefore standard therapy is not established. This case might indicate an efficacy of ADA for secondary gastrointestinal amyloidosis accompanied with AS.


Distinct effect of orphanin FQ in nucleus raphe magnus and nucleus reticularis gigantocellularis on the rat tail flick reflex.
The aim of the present study is to investigate the effects of orphanin FQ (OFQ) microinjected into the nucleus raphe magnus (NRM) and the nucleus reticularis gigantocellularis (NGC) on pain modulation. The tail-flick latency (TFL) was used as a behavioral index of nociceptive responsiveness. The result showed microinjection of OFQ into the NRM significantly increased the TFL, whereas microinjection of OFQ into the NGC decreased the TFL, suggesting the analgesic effect of OFQ in the NRM and the hyperalgesic effect of OFQ in the NGC. As there are three classes of putative pain modulating neurons in the rostral ventromedial medulla (RVM), the hyperalgesic or analgesic effect of OFQ in the RVM might depend upon the different class of the neurons being acted.


Small pupil phacoemulsification using iris sutures: a new method?
A case is presented in which an alternative surgical method for managing poorly dilating pupils preoperatively or intraoperatively was employed. The technique uses iris sutures, is simple, safe, easily reproducible, and reversible, and does not require new devices for pupil enlargement. This new surgical method is appropriate for extracapsular cataract extraction and phacoemulsification or posterior segment surgeries, and maintains pupillary appearance and function postoperatively. Although other techniques are generally available, this technique may be useful in unique situations where other pupil devices or methods are not available.


The effects of target distance on pivot hip, trunk, pelvis, and kicking leg kinematics in Taekwondo roundhouse kicks.
The study purpose was to investigate the effects of target distance on pivot hip, trunk, pelvis, and kicking leg movements in Taekwondo roundhouse kick. Twelve male black-belt holders executed roundhouse kicks for three target distances (Normal, Short, and Long). Linear displacements of the pivot hip and orientation angles of the pelvis, trunk, right thigh, and right shank were obtained through a three-dimensional video motion analysis. Select displacements, distances, peak orientation angles, and angle ranges were compared among the conditions using one-way repeated measure ANOVA (p < 0.05). Several orientation angle variables (posterior tilt range, peak right-tilted position, peak right-rotated position, peak left-rotated position, and left rotation range of the pelvis; peak hyperextended position and peak right-flexed position of the trunk; peak flexed position, flexion range and peak internal-rotated position of the hip) as well as the linear displacements of the pivot hip and the reach significantly changed in response to different target distances. It was concluded that the adjustment to different target distances was mainly accomplished through the pivot hip displacements, hip flexion, and pelvis left rotation. Target distance mainly affected the reach control function of the pelvis and the linear balance function of the trunk.


Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II.
The intracellular concentration of the 27-kDa mammalian heat shock protein, HSP27, increases several-fold after heat and other metabolic stresses and is closely associated with the acquisition of thermotolerance. Posttranslational modifications may also affect the function of HSP27. Heat shock of HeLa cell cultures, or treatment with arsenite, phorbol ester, or tumor necrosis factor, caused a rapid phosphorylation of preexisting HSP27 and the appearance of three phosphorylated isoforms, HSP27 B, C, and D. Digestion with trypsin and fractionation of the peptides by reverse phase high performance liquid chromatography revealed three 32P-labeled phosphopeptides. Microsequence analysis identified peak I as Ala76-Leu77-Ser78-Arg79 and peak II as Gln80-Leu81-Ser82-Ser83-Gly84-Val85- Ser86-Glu87-Ile88-Arg89; peak III contained the undigested peptide pair Ala76-Arg89. Ser82 was the major site and Ser78 the minor site of phosphorylation. Mutant proteins with Ser78 or Ser82 altered to glycine or Ser78-Ser82 double mutants were phosphorylated to reduced extents in vivo after heat or arsenite treatment. Ser78 and Ser82 (and Ser15) occur in the sequence motif RXXS, which is recognized by ribosomal protein S6 kinase II. Mitogenic stimulation of serum-deprived, Go-arrested Chinese hamster cells with serum, thrombin, or fibroblast growth factor also stimulated phosphorylation of HSP27 Ser78 and Ser82, and mitogenic stimulation and heat shock activated protein kinase activities that phosphorylated HSP27 and protein S6 in vitro. These results suggest that HSP27 may exert phosphorylation-activated functions linked with growth signaling pathways in unstressed cells. A homeostatic function at this level could protect cells from adverse effects of signal transduction systems which may be activated inappropriately during stress.


Xanthene[n]arenes: Exceptionally Large, Bowl-Shaped Macrocyclic Building Blocks Suitable for Self-Assembly.
A new class of macrocycles denoted as "xanthene[n]arenes" was synthesized. In contrast to most other macrocycles, they feature a conformationally restricted bowl shape due to the attached alkyl groups at the linking methylene units. This facilitates the synthesis of cavitands and the self-assembly to molecular capsules via noncovalent interactions. The derivatization potential of the novel macrocycles was demonstrated on the xanthene[3]arene scaffold. Besides a deep cavitand and an oxygen-embedded zigzag hydrocarbon belt[12]arene, a modified macrocycle was synthesized that self-assembles into a hydrogen-bonded tetrameric capsule, demonstrating the potential of xanthene[n]arenes as a new set of macrocyclic building blocks.


Controlling the Spatiotemporal Release of Nerve Growth Factor by Chitosan/Polycaprolactone Conduits for Use in Peripheral Nerve Regeneration.
Tubular polymeric structures have been recognized in the treatment of peripheral nerves as comparable to autologous grafting. The best therapeutic outcomes are obtained with conduits releasing therapeutic molecules. In this study, a new approach for the incorporation of biologically active agent-loaded microspheres into the structure of chitosan/polycaprolactone conduits was developed. The support of a polycaprolactone helix formed by 3D melt extrusion was coated with dopamine in order to adsorb nerve growth factor-loaded microspheres. The complex analysis of the influence of process factors on the coverage efficiency of polycaprolactone helix by nerve grow factor-loaded microspheres was analyzed. Thus, the PCL helix characterized with the highest adsorption of microspheres was subjected to nerve growth factor release studies, and finally incorporated into chitosan hydrogel deposit through the process of electrophoretic deposition. It was demonstrated by chemical and physical tests that the chitosan/polycaprolactone conduit meets the requirements imposed on peripheral nerve implants, particularly mimicking mechanical properties of surrounding soft tissue. Moreover, the conduit may support regrowing nerves for a prolonged period, as its structure and integrity persist upon incubation in lysozyme-contained PBS solution up to 28 days at body temperature. In vitro cytocompatibility toward mHippoE-18 embryonic hippocampal cells of the chitosan/polycaprolactone conduit was proven. Most importantly, the developed conduits stimulate axonal growth and support monocyte activation, the latter is advantageous especially at early stages of nerve regeneration. It was demonstrated that, through the described approach for controlling spatiotemporal release of nerve growth factors, these biocompatible structures adjusted to the specific peripheral nerve injury case can be manufactured.


Bilateral Sciatic Neuropathy after an Autologous Breast Reconstruction in a Massive Weight Loss Patient.
Perioperative compression neuropathy is a known potential complication of prolonged surgical procedures. Sciatic postoperative neuropathy has rarely been reported. We present a 34-year-old woman who underwent right breast reconstruction with supercharged (venous anastomosis) transverse rectus abdominis flap and developed bilateral sciatic compression neuropathy. Her history was remarkable for sleeve gastrectomy 2 years earlier resulting in 105 pound weight loss 1 year before breast reconstruction. During the procedure, the patient was in the supine position for 8 hours and in the semirecumbent position for an additional 2 hours with the torso flexed at 30 degrees and knees flexed at approximately 45 degrees in addition to standard padding. Postoperatively, the patient was found to have loss of sensation and motor paralysis distal to her knees bilaterally. Pain sensation was preserved distally and no other neurological abnormalities were noted. Laboratory tests, magnetic resonance imaging, electromyography, and nerve conduction studies all revealed no evidence of neurological lesions and peroneal or lumbosacral radiculopathy. Motor strength gradually returned to her lower extremities over 4-5 weeks, whereas sensory function continued to improve over 7 weeks. The patient had complete neurological recovery 2 months postoperatively.


Responses of regressor and progressor lines of chickens to intracerebral inoculations of Rous sarcoma virus.
Two-day-old chickens of the Arkansas B1 progressor (Pr) line and the B1 regressor (R) line were inoculated intracerebrally with three dilutions of Rous sarcoma virus. Chickens that died between 7 and 42 days postinoculation were examined for lesions attributable to Rous sarcomas. Mortality was 93% for the progressor chickens as compared with 65% for the regressor chicken. Macroscopic lesions were found on the head in 64 chickens, as hemorrhage in the brain in 38, on the heart in 15, on the liver in 9, and in the parenchyma of the brain in one chicken, from a total of 117 chickens inoculated. Surviving chickens were inoculated in the wingweb with Rous sarcoma virus. Of the progressor line chickens three of four developed tumors and two died. The third chicken exhibited abnormal neurological behavior. Of the regressor line, 15 of 20 were immune and of the five that developed tumors, four had complete regressions. The fifth chicken also showed neurological abnormality. The two chickens with neurological dysfunction were sacrificed, and their histopathology examinations revealed lesions in the brain with features belonging to Rous sarcomas, paralleling those reported for other types of sarcomas.


A refined method for the detection of baculovirus occlusion bodies in forest terrestrial and aquatic habitats.
A sensitive and efficient method was developed for the detection of genetically modified and wild-type baculovirus occlusion bodies (OB) in forest terrestrial and aquatic habitats. The protocol facilitates the analysis of a large number of samples collected and frozen to maintain viral integrity. Lyophilization was used to standardize the size of both field-collected soil samples and test substrates inoculated with OBs for the determination of minimum detection threshold. To simulate natural conditions, terrestrial test substrates were inoculated at a standardized moisture content determined using a soil pressure plate apparatus. OBs, extracted from lyophilized test substrates by washing, sieving and centrifugation, were subjected to alkaline lysis and viral DNA isolated using a purchased DNA purification kit. PCR amplified DNA was visualized using agarose gel electrophoresis. Minimum detection thresholds in terrestrial substrates were 10(3), 10(2), 10(2) and 10(1) OBs from 0.5 g of lyophilized L, F-H and mineral soil horizons, and 1.0 ml of leachate, respectively. Detection thresholds in aquatic substrates were 10(0) and 10(3) OBs from 1.0 ml of pond water and 1.0 g of bottom sediment, respectively.


The fertility-related concerns, needs and preferences of younger women with breast cancer: a systematic review.
Breast cancer is the most commonly diagnosed type of cancer in reproductive aged women. Adjuvant systemic therapy is recommended in most women and has been demonstrated to reduce the risk of recurrence and increase survival. However, there may be a negative impact of adjuvant systemic therapy on fertility as well as on subsequent quality of life. There are a number of fertility preservation options currently available and relevant information regarding these options should be provided prior to commencing adjuvant treatment. The aim of the review is to identify the fertility-related needs, concerns and preferences of young women with early breast cancer. The databases MEDLINE and EMBASE were searched from 1988 onwards using keywords, and examining reference lists. Of the 499 articles identified, 20 met eligibility criteria and were reviewed. Multiple fertility-related information needs specific to this group regarding menstrual changes and potential infertility attitudes to, and actual decisions made regarding, pregnancy breastfeeding and contraception emerged. Information on fertility-related decisions was rated as important, and the preferred methods for obtaining this information was consultation with a specialist or a decision aid early in the treatment plan. There is limited research about fertility-related needs, and even less on contraceptive preferences and the attitudes of health care providers towards fertility-related issues. No studies describing the development of tools to assist with decisions about fertility-related choices were identified. Young women with early breast cancer have specific fertility- and menopause-related needs and concerns, which are commonly not adequately addressed or discussed prior to commencing adjuvant therapy.


Small-volume resuscitation restores hemorrhage-induced microcirculatory disorders in rat pancreas.
Pancreatic hypoxia/ischemia, as a consequence of shock-induced microcirculatory failure, is considered a causative factor in the initiation and/or progression of pancreatic tissue injury. The aim of this study was to compare the effects of "small volume resuscitation" with conventional isovolemic colloid and hypervolemic crystalloid resuscitation on pancreatic microcirculation after hemorrhagic shock. Randomized, controlled intervention trial. University laboratory. Twenty-three male Sprague-Dawley rats anesthetized with á-chloralose mechanically and ventilated. Rats subjected to 1 hr of hemorrhagic shock (mean arterial pressure of 40 mm Hg) were resuscitated with lactated Ringer's solution (four-fold shed volume/20 mins), 10% hydroxyethyl starch (shed volume/5 mins), or 7.2% sodium chloride-10% hydroxyethyl starch (10% shed volume/2 mins). The microcirculation of pancreatic acinar tissue was studied by means of intravital fluorescence microscopy and laser Doppler flowmetry. At 1 hr after resuscitation, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux were found to be significantly increased when compared with those values in the shock state. However, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux did not completely return to preshock values, regardless of the type of fluid used for resuscitation. At 15 mins and 1 hr after resuscitation, shock-induced capillary perfusion failure (reduction of functional capillary density) was restored to 91% to 94% of baseline values in all groups. Pancreatic capillary narrowing, indicating microvascular endothelial cell swelling, was abolished by resuscitation with both isotonic hydroxyethyl starch and hypertonic hydroxyethyl starch (p<.05 vs. lactated Ringer's solution). Despite replacement of only 10% of actual blood loss, small-volume resuscitation with hypertonic hydroxyethyl starch is as effective as the ten-fold volume of isotonic hydroxyethyl starch and, due to prevention of microvascular endothelial cell swelling, superior to the 40-fold volume of isotonic lactated Ringer's solution in regard to restoration of the shock-induced microcirculatory disturbances of rat pancreatic acinar tissue.


Dynamically weighted clustering with noise set.
Various clustering methods have been applied to microarray gene expression data for identifying genes with similar expression profiles. As the biological annotation data accumulated, more and more genes have been organized into functional categories. Functionally related genes may be regulated by common cellular signals, thus likely to be co-expressed. Consequently, utilizing the rapidly increasing functional annotation resources such as Gene Ontology (GO) to improve the performance of clustering methods is of great interest. On the opposite side of clustering, there are genes that have distinct expression profiles and do not co-express with other genes. Identification of these scattered genes could enhance the performance of clustering methods. We developed a new clustering algorithm, Dynamically Weighted Clustering with Noise set (DWCN), which makes use of gene annotation information and allows for a set of scattered genes, the noise set, to be left out of the main clusters. We tested the DWCN method and contrasted its results with those obtained using several common clustering techniques on a simulated dataset as well as on two public datasets: the Stanford yeast cell-cycle gene expression data, and a gene expression dataset for a group of genetically different yeast segregants. Our method produces clusters with more consistent functional annotations and more coherent expression patterns than existing clustering techniques. Supplementary data are available at Bioinformatics online.


An experimental test of a model for repeated Ca2+ spikes in osteoblastic cells.
A model for cytosolic Ca2+ spikes is presented that incorporates continual influx of Ca2+, uptake into an intracellular compartment, and Ca(2+)-induced Ca2+ release from the compartment. Two versions are used. In one, release is controlled by explicit thresholds, while in the other, release is a continuous function of cytosolic and compartmental [Ca2+]. Some model predictions are as follows. Starting with low Ca2+ influx and no spikes: (1) induction of spiking when Ca2+ influx is increased. Starting with spikes: (2) increase in magnitude and decrease in frequency when influx is reduced; (3) inhibition of spiking if influx is greatly reduced; (4) decrease in the root-mean-square value when influx is increased; and (5) elimination of spiking if influx is greatly increased. Since there is good evidence that hyperpolarizing spikes reflect cytosolic Ca2+ spikes, we used electrophysiological measurements to test the model. Each model prediction was confirmed by experiments in which Ca2+ influx was manipulated. However, the original spike activity tended to return within 5-30 min, indicating a cellular resetting process.


Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat.
Repeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET). During ET, there is an imbalance in pro- and anti-inflammatory cytokine and chemokine production, leading to a dysregulated immune response. HIV-1 viral proteins are known to have an adverse effect on the immune system. However, the effects of HIV-1 viral proteins during ET have not been investigated. In this study, HIV-1 transgenic (HIV-1Tg) rats and control F344 rats (n = 12 ea) were randomly treated with 2 non-pyrogenic doses of LPS (LL) to induce ET, or saline (SS), followed by a high challenge dose of LPS (LL+L, SS+L) or saline (LL+S, SS+S). The gene expression of 84 cytokines, chemokines, and their receptors in the brain and spleen was examined by relative quantitative PCR using a PCR array, and protein levels in the brain, spleen, and serum of 7 of these 84 genes was determined using an electrochemiluminescent assay. In the spleen, there was an increase in key pro-inflammatory (IL1α, IL-1β, IFN-γ) and anti-inflammatory (IL-10) cytokines, and inflammatory chemokines (Ccl2, Ccl7, and Ccl9,) in response to LPS in the SS+L and LL+L (ET) groups of both the HIV-1Tg and F344 rats, but was greater in the HIV-1Tg rats than in the F344. In the ET HIV-1Tg and F344 (LL+L) rats in the spleen, the LPS-induced increase in pro-inflammatory cytokines was diminished and that of the anti-inflammatory cytokine was enhanced compared to the SS+L group rats. In the brain, IL-1β, as well as the Ccl2, Ccl3, and Ccl7 chemokines were increased to a greater extent in the HIV-1Tg rats compared to the F344; whereas Cxcl1, Cxcl10, and Cxcl11 were increased to a greater extent in the F344 rats compared to the HIV-1Tg rats in the LL+L and SS+L groups. Our data indicate that the continuous presence of HIV-1 viral proteins can have tissue-dependent effects on endotoxin-induced cytokine and chemokine expression in the ET state.


Experimental observations and numerical modelling of diffusion-driven crystallisation processes.
This paper reports experimental results and modelling on the crystallisation processes induced by counter diffusion method of a precipitant agent in a lysozyme protein solution. Comparison between experimental observations and numerical simulations in the presence of convection and sedimentation and without them (suppressed using gel) provides a validation of the model. Different values of the initial protein concentration are used, in order to investigate the effects of supersaturation conditions on the process, and in particular on nucleation. The model and the experimental approach may represent a useful methodology for the determination of the parameters and conditions that may lead to protein crystallisation. A Mach-Zehnder interferometer is used to monitor the transport dynamics in situ in the fluid phase by observing the compositional field. The effect of the solute transport gives rise to a "nucleation front" that propagates inside the protein solution. The crystal formation, caused by progressing of the front, results in a modulation in time and in space (similar to Liesegang patterns), due to the non-linear interplay among transport, crystal nucleation and growth. Both experimental observation and numerical modelling show spatial and size distributions of crystals that demonstrate comparable evidences of the phenomena.


Effective Prevention of Proximal Junctional Failure in Adult Spinal Deformity Surgery Requires a Combination of Surgical Implant Prophylaxis and Avoidance of Sagittal Alignment Overcorrection.
Propensity score matched analysis of a multi-center prospective adult spinal deformity (ASD) database. Evaluate if surgical implant prophylaxis combined with avoidance of sagittal overcorrection more effectively prevents proximal junctional failure (PJF) than use of surgical implants alone. PJF is a severe form of proximal junctional kyphosis (PJK). Efforts to prevent PJF have focused on use of surgical implants. Less information exists on avoidance of overcorrection of age-adjusted sagittal alignment to prevent PJF. Surgically treated ASD patients (age ≥18 yrs; ≥5 levels fused, ≥1 year follow-up) enrolled into a prospective multi-center ASD database were propensity score matched (PSM) to control for risk factors for PJF. Patients evaluated for use of surgical implants to prevent PJF (IMPLANT) versus no implant prophylaxis (NONE), and categorized by the type of implant used (CEMENT, HOOK, TETHER). Postoperative sagittal alignment was evaluated for overcorrection of age-adjusted sagittal alignment (OVER) versus within sagittal parameters (ALIGN). Incidence of PJF was evaluated at minimum 1 year postop. Six hundred twenty five of 834 eligible for study inclusion were evaluated. Following PSM to control for confounding variables, analysis demonstrated the incidence of PJF was lower for IMPLANT (n = 235; 10.6%) versus NONE (n = 390: 20.3%; P < 0.05). Use of transverse process hooks at the upper instrumented vertebra (HOOK; n = 115) had the lowest rate of PJF (7.0%) versus NONE (20.3%; P < 0.05). ALIGN (n = 246) had lower incidence of PJF than OVER (n = 379; 12.0% vs. 19.2%, respectively; P < 0.05). The combination of ALIGN-IMPLANT further reduced PJF rates (n = 81; 9.9%), while OVER-NONE had the highest rate of PJF (n = 225; 24.2%; P < 0.05). Propensity score matched analysis of 625 ASD patients demonstrated use of surgical implants alone to prevent PJF was less effective than combining implants with avoidance of sagittal overcorrection. Patients that received no PJF implant prophylaxis and had sagittal overcorrection had the highest incidence of PJF. 3.


Acute Neuromuscular and Microvascular Responses to Concentric and Eccentric Exercises With Blood Flow Restriction.
Lauver, JD, Cayot, TE, Rotarius, TR, and Scheuermann, BW. Acute neuromuscular and microvascular responses to concentric and eccentric exercises with blood flow restriction. J Strength Cond Res 34(10): 2725-2733, 2020-The purpose of this study was to investigate the effects of the addition of blood flow restriction (BFR) during concentric and eccentric exercises on muscle excitation and microvascular oxygenation status. Subjects (N = 17) were randomly assigned to either a concentric (CON, CON + BFR) or eccentric (ECC, ECC + BFR) group, with one leg assigned to BFR and the other to non-BFR. Surface electromyography and near-infrared spectroscopy were used to measure muscle excitation and microvascular deoxygenation (deoxy-[Hb + Mb]) and [total hemoglobin concentration] during each condition, respectively. On separate days, subjects completed 4 sets (30, 15, 15, 15) of knee extension exercise at 30% maximal torque, and 1 minute of rest was provided between the sets. Greater excitation of the vastus medialis was observed during CON + BFR (54.4 ± 13.3% maximal voluntary isometric contraction [MVIC]) and ECC + BFR (53.0 ± 18.0% MVIC) compared with CON (42.0 ± 10.8% MVIC) and ECC (46.8 ± 9.6% MVIC). Change in deoxy-[Hb + Mb] was greater during CON + BFR (10.0 ± 10.4 μM) than during CON (4.1 ± 4.0 μM; p < 0.001). ECC + BFR (7.8 ± 6.7 μM) was significantly greater than ECC (3.5 ± 4.7 μM; p = 0.001). Total hemoglobin concentration was greater for ECC + BFR (7.9 ± 4.4 μM) compared with ECC (5.5 ± 3.5 μM). The addition of BFR to eccentric and concentric exercises resulted in a significant increase in metabolic stress and muscle excitation compared with non-BFR exercise. These findings suggest that although BFR may increase the hypertrophic stimulus during both modes of contraction, BFR during concentric contractions may result in a greater stimulus.


Assessment of recording bias in pregnancy studies using health care databases: An application to neurologic conditions.
Pre-existing conditions are imperfectly recorded in health care databases. We assessed whether pre-existing neurologic conditions (epilepsy, multiple sclerosis [MS]) were differentially recorded in the presence of major obstetric outcomes (Caesarean delivery, preterm delivery, preeclampsia) in delivery records. We also evaluated the impact of differential recording on measures of frequency and association between the conditions and outcomes. The 2011-2014 Truven Health MarketScan® Commercial Claims Dataset was used to identify pregnancies. We calculated the relative recording of epilepsy and MS at delivery hospitalization compared with a 270-day pre-delivery window both overall and by the presence of major obstetric outcomes. We estimated risk ratios for the association between epilepsy and MS with the outcomes for each ascertainment window. We identified 909 065 pregnancies in women continuously enrolled from 270-days before the delivery date. Of women with epilepsy identified in the pre-delivery window, 73% had the condition coded at delivery. For MS, the proportion was 60%. MS recording at delivery did not vary by obstetric outcomes, however, delivery-coded epilepsy was less likely confirmed in the pre-delivery window in the presence of preeclampsia. Generally, the period of ascertainment did not meaningfully impact risk ratios, however, the risk ratio for preeclampsia associated with epilepsy was 1.67 (95% CI 1.47, 1.90) when epilepsy was ascertained at delivery and 1.26 (95% CI 1.07, 1.48) when epilepsy was ascertained in the pre-delivery window (heterogeneity, P = .007). Ascertainment of epilepsy and MS in delivery hospitalization records underestimated prevalence. However, the window of recording generally did not impact risk ratio estimates of associations with obstetric outcomes.


Minimal access compared to sternotomy for aortic root and arch surgery.
Partial upper sternotomy is an established technique for aortic valve surgery in numerous centers. Based on the favorable results, this access can be extended for more complex procedures. We assessed the outcomes of aortic root and arch surgery through partial versus full sternotomy. From January 2013 to December 2020, 100 patients underwent proximal aortic surgery. The minimal access approach was used in 73 patients. Operative variables and outcomes were retrospectively analyzed and compared between both groups. There was no significant difference in cross-clamping and extracorporeal circulation times, as well as no difference in postoperative acute renal failure, stroke, myocardial infarction, and re-exploration for bleeding. However, there was a significant difference in favor of partial upper sternotomy in red blood cell transfusion (0 vs. 234 mL; p = 0.01), postoperative drainage volume (300 vs. 750 mL; p < 0.001), ventilation time (median 3 vs. 24 h; p < 0.001), sepsis (1 [1.4%] vs. 4 [14.8%]; p = 0.02), intensive care unit (median 2 vs. 4 days; p = 0.002) and hospital stay (median 7 vs. 10 days; p < 0.001). Only one patient required intraoperative conversion due to massive bleeding. There was no difference in 30-day mortality between both groups. The partial upper sternotomy approach is safe and feasible for aortic root and arch surgery with morbidity and mortality rates similar to full sternotomy, with the advantages of less blood loss and transfusions need, faster extubation, and shorter length of hospital stay.


Factors associated with the recruitment and retention of dentists in the public sector.
There is an increasing demand for public dental services in Australia, with many community dental clinics unable to meet this demand because of an inadequate number of dentists in the workforce. The aim of this study was to identify factors contributing to the recruitment and retention of dentists in the public sector. A postal questionnaire survey of 180 dentists (response rate 75.6 percent) working in the Victorian public sector was undertaken to investigate the characteristics of public sector dentists, job satisfaction, remuneration, perceptions of public dentistry, future career intentions, and issues that relate to recruitment and retention of staff. Victorian public dentists' main reason for entering the public sector was to work in a community-based setting in a supportive and mentored environment. The main factors related to dentists leaving the public sector were poor remuneration, lack of clinical experience, and frustration with administrative policies. Victoria's oral health workforce shortages in the public sector are mainly attributed to retention issues. The potential for mentoring and a desire for helping those in need were factors attracting dentists to work in the public sector. There was a disproportionate number of female dentists in the public sector compared with the general population, and female dentists had a lower mean salary than male dentists regardless of experience. A range of factors were associated with retention, and gradual frustration because of poor remuneration and lack of professional autonomy were significant reasons for the decision to leave the public sector.


[The application of bacterophages in laboratory diagnostic of cholera.]
The capacity of cholera agent to develop, during the seventh pandemic, the forms differing by attribute of resistance to bacteriophage determines overall complexity of solving problem of their phage-diagnostics. The search of new races of diagnostic cholera phages is actual and in the first instance relates to necessity of confirmation of specific characteristics of cholera agent by efficient, simple and reliable mode. Thereupon, the target was established to search new race of cholera phages being active in relation to phage-resistant to commercial medication of diagnostic phage of strains of cholera comma bacilli of biovar El-Tor. The study used 131 museum resistant to diagnostic cholera phages strain Vibrio cholerae El Tor separated from various sources in 2001-2014. The activity of 25 cholera phages in relation to sampled strains was verified. The most promising for constructing phage medication are three bacteriophages with spectrum of lytic activity as 44%, 53% and 56% correspondingly. Out of number of selected strains only 20 cultures (15%) maintained resistance to all phages. The estimated bacteriophages have different spectrum of lytic activity in relation to cholera comma bacilli El Tor. The new avirulent test-strain was to be found for reproduction and control of cholera diagnostic bacteriophage. So, non-toxigenic culture Vibrio cholerae El Tor 19546 was used. The analysis of received results demonstrated that analyzed cholera phages with high lytic activity can be used in diagnostics of phage-resistant strains of cholera comma bacilli. The actuality of application of phage-diagnostic technique lies in the fact that it requires no expensive equipment and large material expenses.


Analysis of CRE-mediated recombination driven by myosin light chain 1/3 regulatory elements in embryonic and adult skeletal muscle: a tool to study fiber specification.
An increasing number of genes have been implicated in skeletal muscle fiber diversity. To study the contribution of diverse genetic elements to the regulation of fiber-type composition, we generated a transgenic mouse in which CRE recombinase expression is driven by muscle-specific regulatory sequences of the myosin light chain 1/3 locus (MLC). Using ROSA26 conditional reporter mice, we detected expression of the MLC-Cre transgene starting from embryonic day 12.5 (E12.5). By E15, recombination was detected in all muscle-derived structures. Immunohistochemical analysis revealed CRE activity was restricted to fast-twitch (type II) and excluded from slow-twitch (type I) fibers of skeletal muscle. The MLC-Cre transgenic mouse can be used in conjunction with conditional alleles to study both developmental patterning and maintenance of fast fiber-type phenotypes.


Heating characteristics of the TRIPAS hyperthermia system for deep seated malignancy.
A deep heating hyperthermia device TRIPAS (a triapplicator system) consisting of three independent, dielectrically loaded horn applicators operating in phase at 300 MHz was investigated. The heating characteristics produced by this hyperthermia system were analyzed by means of thermochromic liquid-crystal cards and a modified CDRH (Center for Devices and Regulatory Health) elliptical phantom. Both homogenous and inhomogeneous phantoms were used, simulating high and low permittivity tissues (muscle and lung). These equivalent tissues were made of polyacrylamide gel. The semiquantitative heating pattern analysis showed a central heating of 1/3 of maximum heating at a depth of 10 cm in both homogenous (muscle) and heterogenous (muscle/fat) phantoms. Also more uniform temperature/SAR distributions were generated in muscle equivalent material than those in lung.


Hepatosplenic Cat-Scratch Disease in Children and the Positive Contribution of 18F-FDG Imaging.
Two patients were referred to our hospital because of suspected malignancy. In patient 1, a 4-year-old boy, a F-FDG PET scan showed an enlarged liver with multiple FDG-positive nodular lesions. In patient 2, a 16-year-old boy, a FDG PET-(low-dose) CT showed an enlarged liver and spleen with multiple nodular lesions and a solitary hypodense nodule adjacent to the pancreatic head. The lesions were thought to originate from infectious disease or lymphoma. Polymeric chain reaction (PCR) on a liver biopsy was positive for Bartonella henselae. Both patients were treated with antibiotics and recovered completely.


Casein kinase 2 Is activated and essential for Wnt/beta-catenin signaling.
Wnt/beta-catenin signaling is essential to early development. Activation of Frizzled-1 by Wnts induces nuclear accumulation of beta-catenin and activation of Lef/Tcf-dependent gene expression. Casein kinase 2 has been shown to affect Wnt/beta-catenin signaling. How casein kinase 2 exerts an influence in Wnt signaling is not clear; casein kinase 2 has been reported to be constitutively active (i.e. not regulated). Herein we show to the contrary that casein kinase 2 activity is rapidly and transiently increased in response to Wnt3a stimulation and is essential for Wnt/beta-catenin signaling. Chemical inhibition of casein kinase 2 or suppression of its expression blocks Frizzled-1 activation of Lef/Tcf-sensitive gene expression. Treatment with pertussis toxin or knock down of Galpha(q) or Galpha(o) blocks Wnt stimulation of casein kinase 2 activation, as does suppression of the phosphoprotein Dishevelled, demonstrating that casein kinase 2 is downstream of heterotrimeric G proteins and Dishevelled. Expression of a constitutively active mutant of either Galpha(q) or Galpha(o) stimulates casein kinase 2 activation and Lef/Tcf-sensitive gene expression. Thus, casein kinase 2 is shown to be regulated by Wnt3a and essential to stimulation of the Frizzled-1/beta-catenin/Lef-Tcf pathway.


Data-Independent Acquisition Mass Spectrometry To Quantify Protein Levels in FFPE Tumor Biopsies for Molecular Diagnostics.
Mass spectrometry-based protein quantitation is currently used to measure therapeutically relevant protein biomarkers in CAP/CLIA setting to predict likely responses of known therapies. Selected reaction monitoring (SRM) is the method of choice due to its outstanding analytical performance. However, data-independent acquisition (DIA) is now emerging as a proteome-scale clinical assay. We evaluated the ability of DIA to profile the patient-specific proteomes of sample-limited tumor biopsies and to quantify proteins of interest in a targeted fashion using formalin-fixed, paraffin-embedded (FFPE) tumor biopsies ( n = 12) selected from our clinical laboratory. DIA analysis on the tumor biopsies provided 3713 quantifiable proteins including actionable biomarkers currently in clinical use, successfully separated two gastric cancers from colorectal cancer specimen solely on the basis of global proteomic profiles, and identified subtype-specific proteins with prognostic or diagnostic value. We demonstrate the potential use of DIA-based quantitation to inform therapeutic decision-making using TUBB3, for which clinical cutoff expression levels have been established by SRM. Comparative analysis of DIA-based proteomic profiles and mRNA expression levels found positively and negatively correlated protein-gene pairs, a finding consistent with previously reported results from fresh-frozen tumor tissues.


Electrochemically induced cascade reaction for the assembly of libraries of biologically relevant 1,4-benzoxazine derivatives.
The scope and mechanism of an electrochemically induced cascade reaction, which leads to highly substituted 1,4-benzoxazine derivatives, have been explored through the variation of the structure of the o-azaquinone mediator. This reaction sequence, wherein both cycloaddition partners are generated in situ, at room temperature, under metal-free conditions, allows the regiospecific inverse-electron-demand Diels-Alder (IEDDA) reaction of an o-azaquinone heterodiene and a secondary alkylenamine dienophile, two chemically nonaccessible unstable entities. The cascade reaction was found to be general with electron-poor o-azaquinone entities generated from substituted 2-aminoresorcinol substrates. In the case of o-aminophenol derivatives which lack the 2-hydroxyl group, the generated o-azaquinone species failed to catalyze the oxidation of the amine to the corresponding imine, precursor of the enamine dienophile, because the absence of an intramolecular hydrogen bond at the origin of a highly reactive Schiff base cyclic transition state. To overcome this problem, a tandem oxidation-IEDDA reaction, in which the o-azaquinone is generated in the presence of a preformed enamine, has been developed as an alternative. These one-pot methodologies, which offer the opportunity to introduce variations in both cycloaddition partners, should be particularly useful for the development of libraries of biologically relevant 1,4-benzoxazine derivatives.


Identification of intermediately virulent Rhodococcus equi isolates from pigs.
We recently reported the existence of Rhodococcus equi isolates with at least three virulence levels, isolated from AIDS patients: virulent R. equi having 15- to 17-kDa antigens that kills mice with 10(6) cells, intermediately virulent R. equi having a 20-kDa antigen that kills mice with 10(7) cells, and avirulent R. equi that does not kill mice with 10(8) cells or more (S. Takai, Y. Imai, N. Fukunaga, Y. Uchida, K. Kamisawa, Y. Sasaki, S. Tsubaki, and T. Sekizaki, J. Infect. Dis. 172:1306-1311, 1995). Virulent R. equi having the 15- to 17-kDa antigens has been isolated frequently from horses and their environment, but the source of intermediately virulent R. equi having the 20-kDa antigen is poorly understood. There are many reports of the isolation of R. equi from the lymph nodes of pigs with and without lesions resembling those of tuberculosis. Therefore, we analyzed antigens of R. equi isolates from the submaxillary lymph nodes of pigs by immunoblotting with monoclonal antibodies against these virulence-associated antigens. Immunoblots of whole-cell antigen preparations of R. equi pig isolates revealed the presence of the 20-kDa antigen in almost all the pig isolates studied, and these isolates were intermediately virulent for mice. We also demonstrated that the expression of the 20-kDa antigen and its pathogenicity in mice were associated strongly with the presence of five large, distinct plasmids of 70 to 95 kb; two of the five plasmids from pig isolates were the same sizes as those from human isolates. These results suggest that R. equi having the 20-kDa antigen exists in the submaxillary lymph nodes of pigs and that the source of infection in some human cases might be associated with pigs and their environment.


Diode-pumped, continuous-wave Tm:YAIO3 laser.
A continuous-wave, diode-pumped, room-temperature Tm:YAlO3 laser was built, characterized, and compared with a theoretical model. Spectroscopic parameters of the laser crystal, such as the pump band ((3)H4 manifold) lifetime, the upper laser level ((3)F4 manifold) lifetime, and the absorption coefficient were measured. The experimental data were used to calculate the quantum efficiency of Tm self-quenching of the (3)H4 manifold.


Membrane properties of isolated winter wheat cells in relation to icing stress.
Isolated cell preparations of winter wheat (Triticum aestivum L.) were utilized to examine the effect of ice encasement at -1 degrees C and exposure to ethanol on metabolic and biochemical properties of cells. Following icing and ethanol treatments, passive efflux of amino acids increased gradually with duration of exposure to the stress, and closely paralleled the decline in viability of cells. In contrast, uptake of (86)Rb declined much more rapidly than viability following exposure to icing or ethanol. Electron spin resonance spectroscopy studies revealed no significant change in molecular ordering within the cell membranes following icing or exposure to ethanol, whereas a small but significant increase in order was detected in the noniced controls. O(2) consumption by isolated cells declined only gradually due to icing and ethanol treatments, and remained relatively high even when cell viability was severely reduced. These results indicate that the plasma membrane is a primary site of injury during ice encasement and that damage to the ion transport system is the earliest manifestation of this injury.


Comparing cost per use of 3M Cavilon No Sting Barrier Film with zinc oxide oil in incontinent patients.
This study compares the total cost of treatment, skin-condition management and prevention of skin breakdown of perianal/buttock skin in incontinent patients receiving 3M Cavilon No Sting Barrier Film (Cavilon NSBF) and zinc oxide oil. This single-centre open-label prospective randomised study involved 40 patients with at least moderate skin damage resulting from incontinence. Patients were randomised to receive either zinc oxide oil or Cavilon NSBF and were treated for 14 days. The study products and other treatment-related products used were recorded, as was the time needed to cleanse the application site and apply the product. Use of both products resulted in an improvement in skin condition after 14 days, but this was significantly better with Cavilon NSBF than zinc oxide oil. Cavilon NSBF was more cost-effective as fewer applications were required, less time was spent applying the skin barrier product and faster healing rates were achieved. The cost-effectiveness ratio per treatment group showed an improvement of one point in the total score of the skin-assessment scale costs: 28.36 Euro for Cavilon NSBF versus 98.06 Euro for zinc oxide oil. Both products resulted in an improvement in skin condition after 14 days, but Cavilon NSBF was found to be more cost-effective. This study was supported by an educational grant from 3M.


Environmental stress responses in Lactobacillus: a review.
Environmental stress responses in Lactobacillus, which have been investigated mainly by proteomics approaches, are reviewed. The physiological and molecular mechanisms of responses to heat, cold, acid, osmotic, oxygen, high pressure and starvation stresses are described. Specific examples of the repercussions of these effects in food processing are given. Molecular mechanisms of stress responses in lactobacilli and other bacteria are compared.


What the radiologist should know about postoperative MDCT evaluation of a patient treated with cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy.
Cytoreductive surgery (CRS), often associated with hyperthermic intraperitoneal chemotherapy (HIPEC), is now a well-recognised treatment for most peritoneal malignancies in selected patients. As imaging is frequently performed postoperatively, radiologists are increasingly confronted with postoperative multidetector-row computed tomography (MDCT) examinations in these cases. In this article, after briefly describing the procedures that are currently being performed for the treatment of peritoneal metastases, the normal postoperative MDCT changes that may be encountered after these procedures are described. We then highlight complications that may arise after CRS, depending on the surgery performed, and those related to HIPEC, and illustrate their MDCT features.


Differential expression of the Sesbania rostrata leghemoglobin glb3 gene promoter in transgenic legume and non-legume plants.
The involvement of the Sesbania rostrata glb3 gene promoter NICE (nodule-infected cell expression) element in root-enhanced expression of 5'-Srglb3-uidA-3'nos chimeric gene was investigated in transgenic Nicotiana tabacum plants. The full-length wild-type Srglb3 promoter directed root meristem-enhanced expression in transgenic tobacco plants. The expression pattern of nine selected Srglb3 promoter mutations in the NICE element was examined in transgenic tobacco plants and compared with the pattern observed in nodules of transgenic Lotus corniculatus plants. The results suggest that the highly conserved motifs in the NICE element play an important role in expression in roots of non-legume plants.


Electrophysiological mapping of embryonic mouse hearts: mechanisms for developmental pacemaker switch and internodal conduction pathway.
Understanding sinoatrial node (SAN) development could help in developing therapies for SAN dysfunction. However, electrophysiological investigation of SAN development remains difficult because mutant mice with SAN dysfunctions are frequently embryonically lethal. Most research on SAN development is therefore limited to immunocytochemical observations without comparable functional studies. We applied a multielectrode array (MEA) recording system to study SAN development in mouse hearts acutely isolated at embryonic ages (E) 8.5-12.5 days. Physiological heart rates were routinely restored, enabling accurate functional assessment of SAN development. We found that dominant pacemaking activity originated from the left inflow tract (LIFT) region at E8.5, but switched to the right SAN by E12.5. Combining MEA recordings and pharmacological agents, we show that intracellular calcium (Ca(2+))-mediated automaticity develops early and is the major mechanism of pulse generation in the LIFT of E8.5 hearts. Later in development at E12.5, sarcolemmal ion channels develop in the SAN at a time when pacemaker channels are down-regulated in the LIFT, leading to a switch in the dominant pacemaker location. Additionally, low micromolar concentrations of tetrodotoxin (TTX), a sodium channel blocker, minimally affect pacemaker rhythm at E8.5-E12.5, but suppress atrial activation and reveal a TTX-resistant SAN-atrioventricular node (internodal) pathway that mediates internodal conduction in E12.5 hearts. Using a physiological mapping method, we demonstrate that differential mechanistic development of automaticity between the left and right inflow tract regions confers the pacemaker location switch. Moreover, a TTX-resistant pathway mediates preferential internodal conduction in E12.5 mouse hearts.


In Ssarch of new anti-bacterial target genes: a comparative/structural genomics approach.
We outline a joint academic/industrial (CNRS/AVENTIS) functional genomics project aiming at the discovery of new anti-bacterial gene targets. Starting from all publicly available bacterial genomes, a subset of the most evolutionary conserved protein-coding genes has been identified. We retained genes with clear homolog in E. coli and at least one gram-positive bacterium among B.subtilis, M. tuberculosis, L. lactis or S. pyogenes. This subset was further reduced to genes encoding non-membrane proteins of unknown or hypothetical functions. The 221 E. coli Open Reading Frames (ORFs) identified through this comprehensive bioinformatic analysis are now submitted to a systematic 3-D structure determination protocol including cloning, protein expression and purification, crystallisation and X-ray diffraction. Our strategy was designed to focus on promising wide-spectrum targets as well as original biochemical pathways. Bioinformatics is used throughout all phases of project, including the initial large-scale comparative genomics analyses, the purification/expression and crystallisation stages for the detection of helpful sequence-specific features (e.g. cofactor binding motifs, non-structured N- or C- term extremities, etc ), and finally for the interpretation of the structures in conjunction with multiple sequence alignments for the identification of key residues, interaction areas on molecular surfaces, and overall function predictions.


The evolving roles of Operating Department Practitioners in contemporary healthcare: A service evaluation.
A mixed method study was undertaken to capture quantitative and qualitative data in relation to the contemporary roles and skills of Operating Department Practitioners. The data provide evidence that Operating Department Practitioners take opportunities to widen their knowledge skills and practice, with over 37% of the sample completing a mentorship qualification and 14% having completed or studying towards a postgraduate or Master's Degree. The study provides evidence of the development in the roles of the Operating Department Practitioner and suggests that Operating Department Practitioners offer an eclectic mix of skills which are delivered in a variety of clinical settings. It is recognised that Operating Department Practitioners have the potential to further improve patient safety and service delivery in roles other than those historically associated with the profession.


Outcomes of multimodality breast screening for women at increased risk of familial breast cancer.
While population-based breast screening for women over the age of 50 years is a generally accepted and proven health strategy, the role of breast screening specifically among women at high risk of familial breast cancer has remained controversial. Indeed, there are very few services specifically offering a breast-screening program for women at high risk of familial breast cancer. In 1999 a Familial Breast Cancer Screening Clinic (FBCSC) was established at the North Brisbane BreastScreen Queensland Service to provide a regular multimodality screening program utilizing clinical breast examination, breast ultrasound, and mammography for women at higher risk of hereditary breast cancer and with entry into the program commencing from the age of 30 years. Since its inception, a total of 2440 women have participated in the FBCSC. A total 7051 breast-screening examinations have been performed on these participants, with 53 breast cancers being diagnosed, including 8 in situ ductal carcinomas, 38 invasive ductal carcinomas, and 7 invasive lobular carcinomas. The mean size of the cancers was 16 mm (range = 1-45 mm), and of the 45 invasive cancers, 60% were less than or equal to 15 mm in size. The overall axillary node positive rate was 24.5% (13/53). The invasive cancer detection rate for first-round screening was 8.3 cancers per 1000 women screened, with 5.2 cancers per 1000 women detected on subsequent round screening. The results from this service demonstrate that multimodality screening for women at high risk of familial breast cancer and including women of younger age is effective and appropriate, with very acceptable cancer detection rates and pathological cancer characteristics being observed consistent with early-stage detection. The colocated siting of this service within a BreastScreen Queensland facility has proven to be efficient and cost effective.


Loss- and gain-of-function mutations in the F1-HAMP region of the Escherichia coli aerotaxis transducer Aer.
The Escherichia coli Aer protein contains an N-terminal PAS domain that binds flavin adenine dinucleotide (FAD), senses aerotactic stimuli, and communicates with the output signaling domain. To explore the roles of the intervening F1 and HAMP segments in Aer signaling, we isolated plasmid-borne aerotaxis-defective mutations in a host strain lacking all chemoreceptors of the methyl-accepting chemotaxis protein (MCP) family. Under these conditions, Aer alone established the cell's run/tumble swimming pattern and modulated that behavior in response to oxygen gradients. We found two classes of Aer mutants: null and clockwise (CW) biased. Most mutant proteins exhibited the null phenotype: failure to elicit CW flagellar rotation, no aerosensing behavior in MCP-containing hosts, and no apparent FAD-binding ability. However, null mutants had low Aer expression levels caused by rapid degradation of apparently nonnative subunits. Their functional defects probably reflect the absence of a protein product. In contrast, CW-biased mutant proteins exhibited normal expression levels, wild-type FAD binding, and robust aerosensing behavior in MCP-containing hosts. The CW lesions evidently shift unstimulated Aer output to the CW signaling state but do not block the Aer input-output pathway. The distribution and properties of null and CW-biased mutations suggest that the Aer PAS domain may engage in two different interactions with HAMP and the HAMP-proximal signaling domain: one needed for Aer maturation and another for promoting CW output from the Aer signaling domain. Most aerotaxis-defective null mutations in these regions seemed to affect maturation only, indicating that these two interactions involve structurally distinct determinants.


Effects of iodine deficiency on thyroid hormone metabolism and the brain in fetal rats: the role of the maternal transfer of thyroxin.
Thyroid hormones, thyroxin (T4) and 3,5,3'-triiodothyronine (T3), of maternal origin, are available to the mammalian embryo early in development. However, after the onset of fetal thyroid function, they are of both fetal and maternal origin. Maternal T4 has a protective effect on the fetal brain in cases of congenital hypothyroidism. In severe iodine deficiency, maternal T4 is low, although T3 is normal; the developing embryo is markedly T4-deficient; and T3 deficiency increases with gestational age. In contrast to mechanisms in the hypothyroid fetus from a normal mother, the low T4 of the iodine-deficient mother prevents any protective effects on the fetal brain. Thyroid hormone deficiency of the iodine-deficient fetus, including the brain, is more severe and prolonged than it is in the cases of maternal or fetal thyroid failures. These findings may help to explain the relationship between severe maternal hypothyroxinemia and the severe central nervous system damage of the neurological endemic cretin.


Effect of liposomal composition on photoactivated liposome fusion.
Bennett and O'Brien [(1995) Biochemistry 34, 3102] showed that the ultraviolet light exposure of two-component large unilamellar liposomes (LUV) composed of a 3:1 molar mixture of dioleoylphosphatidylethanolamine (DOPE) and 1,2-bis[10-(2'-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphatidyl- choline (bis-SorbPC) facilitated liposome fusion. The rate and extent of liposome fusion was dependent on the extent of photopolymerization, the temperature, and the pH. Examination of the temperature dependence of fusion of photolyzed and unphotolyzed liposomes demonstrated that an enhancement of the rate of fusion occurred in the temperature range associated with the initial appearance of precursors to the inverted cubic (QII) phase [Barry et al. (1992) Biochemistry 31, 10114]. Here, the effect of the molar lipid ratio of the DOPE/bis-SorbPC liposomes on the temperature for the onset of fusion, i.e. the critical fusion temperature, was characterized by changing the relative amounts of unreactive polymorphic lipid and reactive lamellar lipid. In each case, photopolymerization of bis-SorbPC lowered the critical fusion temperature by ca. 15-20 degrees C. The photoreaction of the bis-SorbPC-containing LUV yields cross-linked poly-SorbPC, enhancing the lateral separation of the DOPE and the polylipid and causing isothermal induction of liposome fusion by lowering the temperature for the onset of fusion. Evidence is presented to support the hypothesis that the critical temperature for fusion of two LUV populations depends on the molar ratio of the monomeric lipids in heterodimers of the two LUV. This analysis indicates that the photopolymerization of appropriately designed LUV can decrease the critical fusion temperature from above to below 37 degrees C.


Conserved arginine residues in synaptotagmin 1 regulate fusion pore expansion through membrane contact.
Synaptotagmin 1 is a vesicle-anchored membrane protein that functions as the Ca2+ sensor for synchronous neurotransmitter release. In this work, an arginine containing region in the second C2 domain of synaptotagmin 1 (C2B) is shown to control the expansion of the fusion pore and thereby the concentration of neurotransmitter released. This arginine apex, which is opposite the Ca2+ binding sites, interacts with membranes or membrane reconstituted SNAREs; however, only the membrane interactions occur under the conditions in which fusion takes place. Other regions of C2B influence the fusion probability and kinetics but do not control the expansion of the fusion pore. These data indicate that the C2B domain has at least two distinct molecular roles in the fusion event, and the data are consistent with a model where the arginine apex of C2B positions the domain at the curved membrane surface of the expanding fusion pore.


Determination of 142 pesticides in fruit- and vegetable-based infant foods by liquid chromatography/electrospray ionization-tandem mass spectrometry and estimation of measurement uncertainty.
A liquid chromatographic/electrospray ionization-tandem mass spectrometric method was developed and validated to determine 142 pesticides in fruit- and vegetable-based infant foods, including apples, apples and bananas, pears, bananas, apple juice, peas, sweet potatoes, creamed corn, squash, and carrots. Pesticides were extracted from infant foods by using the procedure known as the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. Quantification was based on matrix-matched standard calibration curves with the use of an isotopically labeled standard or a chemical analogue as the internal standard to obtain method accuracy. The method performance parameters, including overall recovery, intermediate precision, and measurement uncertainty, were evaluated on the basis of a nested design. The performance results were calculated by using a compiled SAS program that provided a semiautomated procedure for handling a large number of calculations in a few seconds. In general, the overall recoveries, for spiking levels of 10, 50, and 80 microg/kg, fell in a range of 81-110%, intermediate precisions were <20%, and measurement uncertainties were <40%. Chlorimuron-ethyl, ethofenprox, haloxyfop, naptalam, primisulfuron-methyl, pyridalyl, pyridate, quizalofop, and tebufenozide were the method problematic pesticides that had large measurement uncertainty (>40%) due to low recovery andlor poor repeatability. The method provided an analytical range of 1-100 microg/kg with the lowest concentration level at 1 microg/kg for all pesticides (signal-to-noise ratio of >10), except for aclonifen at 5 microg/kg.


Phytostabilization potential of Jatropha curcas L. in polymetallic acid mine tailings.
Greenhouse pot experiments were conducted to determine the growth response, metal tolerance, and phytostabilization potential of Jatropha curcas L The plants were grown on different degrees of multi-metal contaminated acid mine soils (T0, control; T1, moderately and T2, highly contaminated soils) with or without limestone amendments. The order of metal accumulation in J. curcas was roots>stems>leaves. The higher tolerance index (>90%) with no phytotoxic symptoms and growth reduction in T1 showed that this plant has the ability to tolerate polymetallic acid mine tailings. Further, various enzymatic and non-enzymatic antioxidants also actively involved in metal defense mechanism in J. curcas. On the other hand, to alleviate the predominant phytoavailable toxic metals such as Al, Cu, and Pb, different rates (0.1, 0.25, 0.50, and 1%) of limestone amendments were added in both T1 and T2 soils. The growth performance of J. curcas was improved due to the increase in soil pH and decrease in phytoavailable soil A1 (95%), Zn (approximately 75%), and Cu (approximately 65%) contents at 0.50% of lime addition. Based on the inherent tolerance ability of J. curcas in existing adverse environmental conditions without liming, it could be used as a suitable candidate for phytostabilization in acid mine tailings.


CQA 206-291: a novel dopamine agonist in the treatment of Parkinson's disease.
The antiparkinsonian efficacy and tolerability of CQA 206-291, a novel ergoline derivative with potent dopamine agonist properties, were studied during 2 months of treatment in 72 parkinsonian patients. In 36 de novo patients (patients who have not previously been treated with levodopa or dopamine agonists), CQA 206-291 was studied in an open design, while in 36 levodopa-treated patients, CQA 206-291 was studied in a randomized, double-blind, parallel-group, placebo-controlled design. CQA 206-291 induced in both groups a significant antiparkinsonian effect with an effective dose range of 5-30 mg/day. The spectrum of adverse events was similar to what is commonly observed with dopamine agonists. Further studies are required to assess the putative therapeutic advantages of CQA 206-291 when compared to other antiparkinsonian drugs.


The effects of vitamin D deficiency on mandibular bone structure: a retrospective radiological study.
The aim of the study was to evaluate the effects of vitamin D deficiency on the mandibular bone structure by fractal analysis and panoramic morphometric indices. Ninety participants were divided into three groups as 30 individuals with severe vitamin D deficiency, 30 individuals with vitamin D deficiency, and 30 individuals with vitamin D sufficiency. Fractal dimension analysis (FD), panoramic mandibular index (PMI), mandibular cortical index (MCI), and mandibular cortical thickness measurement (CTM) were evaluated on panoramic radiographs. FD values of the patients with vitamin D deficiency were found to be statistically lower than the patients with vitamin D sufficiency (p < 0.05). FD value of supracortical area above the angulus mandible (FD2) in patients with severe vitamin D deficiency was significantly lower than FD values (p = 0.002). There was no statistically significant difference between the groups in the CTM (p > 0.05). PMI was significantly lower in patients with severe vitamin D deficiency (p < 0.001). There was a significant difference in MCI values between the groups (p < 0.05). Vitamin D deficiency causes a decrease in bone mineral density in the mandible, and an increase in alveolar porosity. FD analysis and radiomorphometric indices in panoramic radiographs can be used to assess osteoporotic changes in patients with vitamin D deficiency.


Surveillance for MDR-TB: is there an obligation to ensure treatment for individuals identified with MDR-TB?
This article raises ethical issues that result if individuals, during the course of research to measure the prevalence of drug-resistant tuberculosis, are identified with the disease but are not provided with or referred for appropriate treatment. It draws attention to and applauds recently published World Health Organization guidelines on the subject. Questions posed are: 1) Should treatment be provided for individuals identified through surveillance projects for MDR-TB, whatever their purpose (specific research or 'routine' national prevalence studies)? 2) If treatment availability is a problem, who is responsible for assuring this?


[Characteristics of the aged surgery patient].
In 32 old people selected at random (16 men and 16 women) indicators of the water and mineral salt balance were investigated as well as renal and hepatic functions, nutritional status, serum insulin, thyroxine and triiodothyronine and in 12 also changes after operation. The findings indicate that it is necessary to ensure clinical and biochemical monitoring as well as proper preparation of old people for a planned surgical operation. Old people must be always considered critical patients and it is important to provide extra preoperative and postoperative care.


Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial.
Beneficial effects of tranexamic acid (TA) have been established in surgery and trauma. In ongoing postpartum haemorrhage (PPH), a moderate reduction of blood loss was observed in a previously published randomized controlled trial. Analysis of haemostasis parameters obtained from samples collected as part of this study are presented. Women with PPH >800 ml after vaginal delivery were assigned to receive either TA (4 g over 1 h, then 1 g per h over six h) (TA) or not (H). A non-haemorrhagic group (NH), <800 ml blood loss, was included as postpartum reference. At four time-points (enrolment, +30 min, +2 h, +6 h), haemostasis was assessed. Haemostasis assays were performed blinded to group allocation. Data were expressed as median [interquartiles] and compared with non-parametric tests. In H compared with NH group, D-dimers increase (3730 ng ml(-1) [2468-8493] vs 2649 [2667-4375]; P=0.0001) and fibrinogen and factor II decrease were observed at enrolment and became maximal 2 h later. When comparing TA to H patients, the increase in Plasmin-Antiplasmin-complexes at +30 min (486 ng ml(-1) [340-1116] vs 674 [548-1640]; P=0.03) and D-dimers at +2 h (3888 ng ml(-1) [2688-6172] vs 7495 [4400-15772]; P=0.0001) was blunted. TA had no effect on fibrinogen decrease. This study provides biological evidence of an early increase in D-dimers and plasmin-antiplasmin complexes associated with active post-partum haemorrhage and its attenuation by the early use of a clinically effective high dose of TA, opening the perspective of dose ranging studies to determinate the optimal dose and timing in this setting. ISRCTN09968140.


[Mobilizing community around the lack of preventive measures against crime among 10- and 11-year-old children].
Originality and relevance are not the only factors in the success of innovative programs. Community consensus, expertise and credibility of staff, and evaluative approaches are important as well. Virgule ("Comma"), a program aimed at helping 10- and 11-year-olds who are first offenders, has these characteristics. The temporary hitch in the youth's life is viewed not as a definitive failure but as an opportunity for change. This is Virgule's philosophy: "Changing a period into a comma means changing a difficulty into a reason for progress."


Distribution of ICAM-1 within decidua and placenta and its gestational age-associated changes.
Intercellular adhesion molecule 1 (ICAM-1), a ligand of leukocyte function associated antigen 1 (LFA-1), is present on many cells, including monocyte/macrophages. ICAM-1 is considered to play an important role in the induction and maintenance of inflammatory responses by permitting leukocyte adhesion. Its expression is inducible on endothelial and epithelial cells exposed to various inflammatory cytokines (preceding expression of HLA-DR) and is maturation dependent in certain cell lines. The distribution of ICAM-1 in decidua and placenta was evaluated using peroxidase-antiperoxidase immunohistochemistry. In decidua of first and third trimesters, scattered ICAM-1-staining cells were observed. In placentas of first and third trimesters, all types of trophoblasts stained negatively for ICAM-1. Prior to 10 weeks of gestation, the villous stroma was uniformly ICAM-1 and HLA-DR unreactive. Beginning in the chorionic plate at approximately 10 weeks, scattered ICAM-1-positive stromal cells were observed, whereas stromal cells of the terminal villi revealed no ICAM-1. By 14-16 weeks, approximately 40-50% of the terminal villous stromal cells were ICAM-1 staining. This parallels the 40-50% of the villous stromal cells that share other immunohistochemical markers, such as EB-11, with monocyte/macrophages. The lack of functional maturation of the villous stromal macrophage may explain the rarity of chronic villitis early in gestation.