Online Positive Affect Journaling in the Improvement of Mental Distress and Well-Being in General Medical Patients With Elevated Anxiety Symptoms: A Preliminary Randomized Controlled Trial.
Positive affect journaling (PAJ), an emotion-focused self-regulation intervention, has been associated with positive outcomes among medical populations. It may be adapted for Web-based dissemination to address a need for scalable, evidence-based psychosocial interventions among distressed patients with medical conditions. This study aimed to examine the impact of a 12-week Web-based PAJ intervention on psychological distress and quality of life in general medical patients. A total of 70 adults with various medical conditions and elevated anxiety symptoms were recruited from local clinics and randomly assigned to a Web-based PAJ intervention (n=35) or usual care (n=35). The intervention group completed 15-min Web-based PAJ sessions on 3 days each week for 12 weeks. At baseline and the end of months 1 through 3, surveys of psychological, interpersonal, and physical well-being were completed. Patients evidenced moderate sustained adherence to Web-based intervention. PAJ was associated with decreased mental distress and increased well-being relative to baseline. PAJ was also associated with less depressive symptoms and anxiety after 1 month and greater resilience after the first and second month, relative to usual care. Web-based PAJ may serve as an effective intervention for mitigating mental distress, increasing well-being, and enhancing physical functioning among medical populations. PAJ may be integrated into routine medical care to improve quality of life. ClinicalTrials.gov NCT01873599; https://clinicaltrials.gov/ct2/show/NCT01873599 (Archived by WebCite at http://www.webcitation.org/73ZGFzD2Z).


Evaluation of Cyclic Peptide Inhibitors of the Grb7 Breast Cancer Target: Small Change in Cargo Results in Large Change in Cellular Activity.
Grb7 is an adapter protein, overexpressed in HER2+ve breast and other cancers, and identified as a therapeutic target. Grb7 promotes both proliferative and migratory cellular pathways through interaction of its SH2 domain with upstream binding partners including HER2, SHC, and FAK. Here we present the evaluation of a series of monocyclic and bicyclic peptide inhibitors that have been developed to specifically and potently target the Grb7 SH2-domain. All peptides tested were found to inhibit signaling in both ERK and AKT pathways in SKBR-3 and MDA-MB-231 cell lines. Proliferation, migration, and invasion assays revealed, however, that the second-generation bicyclic peptides were not more bioactive than the first generation G7-18NATE peptide, despite their higher in vitro affinity for the target. This was found not to be due to steric hindrance by the cell-permeability tag, as ascertained by ITC, but to differences in the ability of the bicyclic peptides to interact with and penetrate cellular membranes, as determined using SPR and mass spectrometry. These studies reveal that just small differences to amino acid composition can greatly impact the effectiveness of peptide inhibitors to their intracellular target and demonstrate that G7-18NATE remains the most effective peptide inhibitor of Grb7 developed to date.


Ceramic surface preparations for resin bonding.
To evaluate the effects of hydrofluoric acid (HF) and acidulated phosphate fluoride (APF) primers on differently prepared leucite-containing feldspar ceramic surfaces. Discs of a leucite-containing feldspar ceramic were prepared following the manufacturer's instructions. Surfaces were either polished, grit blasted or prepared with a diamond bur and then subjected to a range of etching procedures using HF or APF. The surface topography was examined using scanning electron microscopy (SEM). Back-scattered imaging, EDS and X-ray diffraction (XRD) were used for microstructural and compositional analysis. The etching process with HF consisted of a preferential attack of the leucite phase relative to the glass but also removed all features of the previous surface preparation. In contrast, APF etching resulted in the formation of surface deposits, superimposed on the surface roughness created by the prior surface preparations. It was not possible to identify the deposits after APF etching using XRD.


To dialyze or not: the patient with metastatic cancer and AKI in the intensive care unit.
AKI severe enough to necessitate renal replacement therapy occurs in approximately 5% of patients admitted to the intensive care unit (ICU) and is associated with in-hospital mortality in excess of 50%. Complicating factors, such as cancer, can increase in-hospital mortality to 85%. Intensivists often expect that consulted nephrologists will provide dialysis when asked to do so, without considering whether it is likely to benefit the patient and therefore is medically and ethically appropriate. In this Attending Rounds, on the basis of the evidence and recommendations in Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis, a clinical practice guideline, a case of anuric AKI in the ICU is presented and analyzed. Woven into the discussion are insights from the clinical and ethics literature on this topic, along with the experience of the author. This Attending Rounds presents an approach to deciding when it is not appropriate to dialyze patients with AKI in the ICU.


The neurodevelopment of empathy in humans.
Empathy, which implies a shared interpersonal experience, is implicated in many aspects of social cognition, notably prosocial behavior, morality and the regulation of aggression. The purpose of this paper is to critically examine the current knowledge in developmental and affective neuroscience with an emphasis on the perception of pain in others. It will be argued that human empathy involves several components: affective arousal, emotion understanding and emotion regulation, each with different developmental trajectories. These components are implemented by a complex network of distributed, often recursively connected, interacting neural regions including the superior temporal sulcus, insula, medial and orbitofrontal cortices, amygdala and anterior cingulate cortex, as well as autonomic and neuroendocrine processes implicated in social behaviors and emotional states. Decomposing the construct of empathy into subcomponents that operate in conjunction in the healthy brain and examining their developmental trajectory provides added value to our current approaches to understanding human development. It can also benefit our understanding of both typical and atypical development.


Alterations in brain metabolism induced by chronic morphine treatment: NMR studies in rat CNS.
High-resolution (500 MHz) multiresonance/multinuclear proton (1H) nuclear magnetic resonance (NMR) spectroscopy was used to detect metabolic changes and cellular injury in the rat brain stem and spinal cord following chronic morphine treatment. Compensatory changes were observed in glycine, glutamate, and inositols in the brain stem, but not the spinal cord, of chronic morphine-treated rats. In spinal cord, increases were detected in lactate and N-acetyl-aspartate (NAA), suggesting that there is anaerobic glycolysis, plasma membrane damage, and altered pH preferentially in the spinal cord of chronic morphine-treated rats.


[Catalytic properties of dust as criteria of its occupational hazards].
The catalytic properties of fire clay (kaolin) and mullet dusts versus quartz, asbestos, and coal ones were studied. Kaolin and mullet were found to have different catalytic capacities mainly of forming free radicals. The dust of kaolin increased the level of superoxide anion radical and hydrogen peroxide in the granulocytic suspension and H2O2/O2 ratio to a lesser extent than that of mullet and quartz. Differences in the catalytic capacity of the examined dusts confirm the findings from the investigations of their effects on plasma lipid peroxidation (LPO). Kaolin and quartz were the least in elevating LPO. As compared with kaolin and quartz, the effects of mullet and asbestos were 2.5 and 6.5 higher, respectively. The substances were different in their genotoxicity.


Tunable optical properties of amorphous Tantala layers in a quantizing structure.
Plasma deposition techniques like ion-beam-sputtering (IBS) are state of the art to manufacture high quality optical components for laser applications. Besides the well optimized process and monitoring systems, the coating material selection is integral to achieve optimum optical performances. Applying the IBS technology, an approach is presented to create novel materials by the direct application of binary oxides in a quantizing structure. By reducing the physical thickness of the high refractive index material to a few nm, within a classical high-low index stack, the electron confinement can be changed. Optical characterizations of the manufactured samples with decreasing quantum well thicknesses result in an increasing blue shift of the absorption gap and offer a method to approximate the effective mass of the high refractive index material in conjunction with theoretical models. Laser-induced damage threshold tests of coating samples prepared with different well thicknesses indicate an increase of the measured threshold values with optical gap energy.


A theoretical study of the binding of phenothiazine derivatives to residues 82-93 of calmodulin.
A theoretical study was performed of the interaction of four phenothiazine derivatives, promethazine, promazine, trifluopromazine, and trifluoperazine, with a fragment (82-93) of calmodulin, held in the alpha-helical conformation. The computations were performed in the framework of the SIBFA 2 procedure (sum of interactions between fragments computed ab initio), which uses analytical formulas based on ab initio self-consistent field computations. The interaction energy is the sum of the intermolecular phenothiazine-oligopeptide interaction energy and of the separate intramolecular energy variations of the phenothiazine and of the side chains of the oligopeptide upon complex formation. The ordering of interaction energies of the four investigated phenothiazines parallels the ordering of their experimentally measured affinities for calmodulin, with a maximum affinity for trifluoperazine. The principal features of the trifluoperazine complex are a short hydrogen bond between the piperazinium proton and one anionic oxygen of Glu 87, and hydrophobic interactions between the piperazinium ring and Val 91 and between the methylene chain and Ala 88, together with partial insertion of the phenothiazine ring and the--CF3 substituent between Phe 89 and Phe 92.


From Black Boxes to Actionable Insights: A Perspective on Explainable Artificial Intelligence for Scientific Discovery.
The application of Explainable Artificial Intelligence (XAI) in the field of chemistry has garnered growing interest for its potential to justify the prediction of black-box machine learning models and provide actionable insights. We first survey a range of XAI techniques adapted for chemical applications and categorize them based on the technical details of each methodology. We then present a few case studies to illustrate the practical utility of XAI, such as identifying carcinogenic molecules and guiding molecular optimizations, in order to provide chemists with concrete examples of ways to take full advantage of XAI-augmented machine learning for chemistry. Despite the initial success of XAI in chemistry, we still face the challenges of developing more reliable explanations, assuring robustness against adversarial actions, and customizing the explanation for different applications and needs of the diverse scientific community. Finally, we discuss the emerging role of large language models like GPT in generating natural language explanations and discusses the specific challenges associated with them. We advocate that addressing the aforementioned challenges and actively embracing new techniques may contribute to establishing machine learning as an indispensable technique for chemistry in this digital era.


Bicaval dual-lumen cannula for venovenous extracorporeal membrane oxygenation: Avalon© cannula in childhood disease.
Severe acute refractory respiratory failure is considered a life-threatening situation, with a high mortality of 40 to 60%. When conservative oxygenation methods fail, a lifesaving measure is the introduction of extracorporeal membrane oxygenation (ECMO). Venovenous ECMO (VV-ECMO) is a preferred modality of support for patients with refractory acute respiratory failure. Specifically, bicaval VV-ECMO is a well-recognized and validated therapy, where single or double periphery venous access is used for the insertion of two differently sized cannulas in order to achieve adequate blood oxygenation. Compared to venoarterial ECMO, in VV-ECMO, the rate of complications, such as thrombosis, bleeding, infection and ischemic events, is lower. On the other hand, the size and insertion location is an obstacle to patient mobilization. This is a considerable problem for patients where the time interval for lung recovery and the bridge to the transplantation is prolonged. To address this issue, a dual-lumen, single venovenous cannula was introduced. Here, by insertion of one single catheter in one target vessel, in a majority of cases in the right internal jugular vein, satisfactory oxygenation of the patient is achieved. In this form, the instituted VV-ECMO enables patient mobility, better physical rehabilitation and facilitates pulmonary extubation and toilet. However, relatively early, after the first short-term reports were published, a relatively high complication rate became evident. In the recent literature, the complication rate using actual commercially available double-lumen venovenous cannula ranges between 5 and 30%. These cases were mostly conjoined to the implantation phase or the early postoperative phase and vary between right heart perforation to migration of the cannula. This review focuses on complications allied to commercially available dual-lumen, single, venovenous cannula implantation, pointing out the critical segments of the implantation process and analyzing the structure of the device.


Safety profile and treatment response of everolimus in different solid tumors: an observational study.
Only few efforts have been taken to investigate the potential existence of disease-specific differences in the safety profile of everolimus. We analyze here the correlation between different patient and tumor characteristics on the safety profile of this molecule. Information on treatment response is also provided. Consecutive patients with metastatic renal cell carcinoma (mRCC), pancreatic neuroendocrine tumors (pNET) or biliary tract cancer were included in this retrospective study. All patients received everolimus 10 mg/day or 5 mg/day. Clinical assessments were performed every 3 weeks. In total, 98 patients were enrolled: 51 with mRCC, 25 with pNET and 22 with biliary tract cancer. The incidence of toxicities (any grade) was 76% with mRCC, 64% with pNET and 95% with biliary tract cancer. Patients with biliary tract cancer also presented a higher frequency of severe toxicities: 64 versus 18% with mRCC and 32% with pNET. Multivariate analysis disclosed that biliary tract cancer (odds ratio [OR]: 23.8; 95% CI: 6.0-117.8; p < 0.0001) is a predictive factor for the development of toxicities during everolimus treatment. No correlations between liver metastasis and toxicities were identified. Disease control rate (DCR) was 45% in mRCC patients, 96% in pNET and 50% for biliary tract cancer patients. pNET tumors were associated with a higher DCR than the mRCC and biliary tract cancer (OR vs mRCC: 66.7; 95% CI: 6.2-276.5; p = 0.004; OR vs biliary tract cancer: 2.6; 95% CI: 0.5-14.2; p = 0.025). This study suggests that the safety profile of everolimus is acceptable in patients with either mRCC or pNET. In addition, the onset of toxicities is associated with an improved DCR. In patients with biliary tract cancer, everolimus is safe but associated with a higher incidence of adverse events.


Hemodynamic evaluation before liver transplantation: insights into the portal hypertensive syndrome.
The cardiac hemodynamics of patients awaiting liver transplantation is complex. Coronary atherosclerosis, a hyperdynamic circulatory state and cirrhotic cardiomyopathy are present to a variable degree in this population. In this contribution to the Symposium on Portal Hypertension, we expand on our published experience with coronary angiography and cardiac hemodynamics at the time of evaluation of candidacy for liver transplantation in a cohort of 161 patients. Although we confirmed the relation of systemic hemodynamics with the degree of liver failure, we noted a higher prevalence of high output heart failure, defined as an increased left ventricular end-diastolic pressure in the setting of an elevated cardiac output, most notably in patients classified as Child C. Most patients with high pulmonary artery pressure also exhibited evidence of elevated left ventricle filling pressures. A low systemic vascular resistance, a marker of arterial vasodilatation, was similar in the presence of atherosclerosis, a condition where impaired vasorelaxation occurs as a result of endothelial dysfunction. The high prevalence of coronary artery disease in this series supports the observations that atherosclerosis is a major issue in the current population with cirrhosis awaiting liver transplantation. A lower sensitivity of noninvasive screening tools for the detection of coronary atherosclerosis is likely the result of the interaction of the hyperdynamic circulation with the performance of these tests.


Efavirenz induces neuronal autophagy and mitochondrial alterations.
Efavirenz (EFV) is a non-nucleoside reverse-transcriptase inhibitor in wide use for the treatment of human immunodeficiency virus infection. Although EFV is generally well tolerated, neuropsychiatric toxicity has been well documented. The toxic effects of EFV in hepatocytes and keratinocytes have been linked to mitochondrial perturbations and changes in autophagy. Here, we studied the effect of EFV on mitochondria and autophagy in neuronal cell lines and primary neurons. In SH-SY5Y cells, EFV induced a drop in ATP production, which coincided with increased autophagy, mitochondrial fragmentation, and mitochondrial depolarization. EFV-induced mitophagy was also detected by colocalization of mitochondria and autophagosomes and use of an outer mitochondrial membrane tandem fluorescent vector. Pharmacologic inhibition of autophagy with 3-methyladenine increased the cytotoxic effect of EFV, suggesting that autophagy promotes cell survival. EFV also reduces ATP production in primary neurons, induces autophagy, and changes mitochondrial morphology. Overall, EFV is able to acutely induce autophagy and mitochondrial changes in neurons. These changes may be involved in the mechanism leading to central nervous system toxicity observed in clinical EFV use.


Pseudohyperplastic squamous cell carcinoma of the penis associated with lichen sclerosus. An extremely well-differentiated, nonverruciform neoplasm that preferentially affects the foreskin and is frequently misdiagnosed: a report of 10 cases of a distinctive clinicopathologic entity.
We present 10 cases of well-differentiated, squamous cell carcinoma of the penis with pseudohyperplastic features. At presentation, the median age was 69 years. Seven of the tumors were multicentric, and the majority preferentially involved the foreskin inner mucosal surface. Grossly the tumors were typically flat or slightly elevated, white and granular, and measured approximately 2 cm. Characteristic histologic features included keratinizing nests of squamous cells with minimal atypia surrounded by a reactive fibrous stroma. In biopsies or individual areas of resected specimens, the differential diagnosis with pseudoepitheliomatous hyperplasia was difficult but when samples of adequate size were available, obvious evidence of infiltration was present. The adjacent squamous epithelium typically showed changes that are known to be associated with squamous cell carcinoma ranging from squamous hyperplasia to low-grade, and in a few cases high-grade, squamous intraepithelial lesions. Well-developed lichen sclerosus was seen in all cases. Patients were treated by circumcision or partial penectomy. With the exception of 1 patient who developed a glans recurrence 2 years after initial circumcision, follow-up after the initial surgical procedure has been uneventful. The majority of penile carcinomas with the high degree of differentiation seen in these cases are in the category of the verruciform tumors, either the verrucous or papillary carcinoma, not otherwise-specified subtypes. Experience with the cases reported in this series indicates that a subset of nonverruciform, often multicentric, tumors with a high degree of differentiation and pseudohyperplastic features occur and preferentially involve the foreskin. Because it was present in all cases, lichen sclerosus may play a precancerous role.


Structural mechanism of endonucleolytic processing of blocked DNA ends and hairpins by Mre11-Rad50.
DNA double-strand breaks (DSBs) threaten genome stability and are linked to tumorigenesis in humans. Repair of DSBs requires the removal of attached proteins and hairpins through a poorly understood but physiologically critical endonuclease activity by the Mre11-Rad50 complex. Here, we report cryoelectron microscopy (cryo-EM) structures of the bacterial Mre11-Rad50 homolog SbcCD bound to a protein-blocked DNA end and a DNA hairpin. The structures reveal that Mre11-Rad50 bends internal DNA for endonucleolytic cleavage and show how internal DNA, DNA ends, and hairpins are processed through a similar ATP-regulated conformational state. Furthermore, Mre11-Rad50 is loaded onto blocked DNA ends with Mre11 pointing away from the block, explaining the distinct biochemistries of 3' → 5' exonucleolytic and endonucleolytic incision through the way Mre11-Rad50 interacts with diverse DNA ends. In summary, our results unify Mre11-Rad50's enigmatic nuclease diversity within a single structural framework and reveal how blocked DNA ends and hairpins are processed.


Analysis of hsp 30, hsp 70 and ubiquitin gene expression in Xenopus laevis tadpoles.
Heat-induced accumulation of hsp 30 mRNA (1.1 kb) during early development of Xenopus laevis was first detectable at the tailbud stage (stage 30-34). This contrasts with heat-induced accumulation of hsp 70 mRNA (2.7 kb) and ubiquitin mRNA (size range = 1.7-3.1 kb), which was first detectable at the mid- to late-blastula stage. Continuous exposure of tadpoles to a 33 degrees C heat shock resulted in a coordinate, transient accumulation of hsp 30, hsp 70 and ubiquitin mRNA. A coordinate, temporal pattern was also observed for the decay of hsp 30, hsp 70 and ubiquitin mRNA in tadpoles recovering at 22 degrees C following a 1 h heat shock at 33 degrees C. Thus, while hsp 30 genes are regulated differently during development compared with hsp 70 and ubiquitin genes, these genes all exhibit a coordinate heat-inducible pattern of expression at the tadpole stage. Levels of alpha-cardiac actin mRNA remained unchanged during continuous heat shock and recovery experiments.


Reversal of insular and microstructural nerve abnormalities following effective surgical treatment for trigeminal neuralgia.
Classical trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder commonly associated with neurovascular compression at the trigeminal nerve root entry zone (REZ). Neurosurgical interventions can relieve TN pain, but the mechanisms underlying these effects are unknown. We determined whether the abnormalities we previously reported at the REZ of TN patients using diffusion tensor imaging (DTI) and brain gray matter (GM) analyses resolve after effective neurosurgical treatment. Twenty-five patients who underwent either microvascular decompression surgery or Gamma Knife radiosurgery for right-sided TN had magnetic resonance imaging scans before and after treatment and were compared with age-matched controls. Cortical thickness and voxel-based morphometry examined specific brain GM we previously reported as abnormal in TN. White matter metrics of fractional anisotropy (FA), mean, radial, and axial diffusivities (MD, RD, and AD, respectively) were extracted bilaterally from each trigeminal REZ. Before treatment, patients had widespread GM abnormalities including thinner ventral anterior insula (vAI) cortex, and REZ microstructural abnormalities (lower FA, and higher MD, RD, and AD) compared with controls. We considered a 75% reduction in pain as effective treatment. The right vAI was the only GM region that normalized toward the level of healthy controls after effective treatment. At the REZ, effective treatment reversed FA, MD, RD, and AD abnormalities and was correlated with pain relief after treatment. These results demonstrate that treatment can effectively resolve pain by normalizing REZ abnormalities, which may influence vAI abnormalities. Future studies should consider DTI as an adjunct to assess the patient outcome and subtle microstructural changes after treatment.


Effects of maternal sensitivity on low birth weight children's academic achievement: a test of differential susceptibility versus diathesis stress.
Differential Susceptibility Theory (DST) postulates that some children are more affected - for better and for worse - by developmental experiences, including parenting, than others. Low birth weight (LBW, 1,500-2,499 g) may not only be a predictor for neurodevelopmental impairment but also a marker for prenatally programmed susceptibility. The aim was to test if effects of sensitive parenting on LBW and very LBW (VLBW, <1,500 g) versus normal birth weight (NBW, ≥2,500 g) children's academic achievement are best explained by a differential susceptibility versus diathesis-stress model of person-X-environment interaction. Nine hundred and twenty-two children ranging from 600 g to 5,140 g birth weight were studied as part of a prospective, geographically defined, longitudinal investigation of neonatal at-risk children in South Germany (Bavarian Longitudinal Study). Sensitive parenting during a structured mother-child interaction task was observed and rated at age 6 years. Academic achievement was assessed with standardized mathematic, reading, and spelling/writing tests at age 8 years. Maternal sensitivity positively predicted the academic achievement of both LBW (n = 283) and VLBW (n = 202) children. Confirmatory-comparative and model-fitting analysis (testing LBW vs. NBW and VLBW vs. NBW) indicated that LBW and VLBW children were more susceptible than NBW to the adverse effects of low-sensitive, but not beneficial effects of high-sensitive parenting. Findings proved more consistent with the diathesis stress than differential-susceptibility model of person-X-environment interaction: LBW and VLBW children's exposure to positive parenting predicted catch-up to their NBW peers, whereas exposure to negative parenting predicted much poorer functioning.


Markers for the identification of late breast cancer recurrence.
Postmenopausal women with early breast cancer are at an ongoing risk of relapse, even after successful surgery and treatment of the primary tumor. The treatment of breast cancer has changed in the past few years because of the discovery of prognostic and predictive biomarkers that allow individualized breast cancer treatment. However, it is still not clear how to identify women that are at high risk of a late recurrence. Clinical parameters are good prognostic markers for early recurrence, but only nodal status and, to a lesser extent, tumor size have proven to be strong prognostic markers for late recurrence. Multi-gene signatures have become widely used for the prediction of overall recurrence risk and tailoring administration of adjuvant chemotherapy, but only a few have been shown to be prognostic for late (distant) relapse. There is a need to accurately identify women who may benefit from extended endocrine therapy but also those who may be spared any additional treatment. Recent results from large clinical trials have shown that the research is going in the right direction, and these results might help to optimize extended endocrine therapy for patients with early breast cancer. However, further research is needed to select individual biomarkers or multi-gene signatures that offer identification of late recurrence specifically and thus justify routine use of these tests in the clinical setting.


A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B.
A clinical isolate of Candida albicans was identified as an erg5 (encoding sterol C22 desaturase) mutant in which ergosterol was not detectable and ergosta 5,7-dienol comprised >80% of the total sterol fraction. The mutant isolate (CA108) was resistant to fluconazole, voriconazole, itraconazole, ketoconazole, and clotrimazole (MIC values, 64, 8, 2, 1, and 2 microg ml(-1), respectively); azole resistance could not be fully explained by the activity of multidrug resistance pumps. When susceptibility tests were performed in the presence of a multidrug efflux inhibitor (tacrolimus; FK506), CA108 remained resistant to azole concentrations higher than suggested clinical breakpoints for C. albicans (efflux-inhibited MIC values, 16 and 4 microg ml(-1) for fluconazole and voriconazole, respectively). Gene sequencing revealed that CA108 was an erg11 erg5 double mutant harboring a single amino acid substitution (A114S) in sterol 14alpha-demethylase (Erg11p) and sequence repetition (10 duplicated amino acids), which nullified C22 desaturase (Erg5p) function. Owing to a lack of ergosterol, CA108 was also resistant to amphotericin B (MIC, 2 microg ml(-1)). This constitutes the first report of a C. albicans erg5 mutant isolated from the clinic.


An in vitro comparison of surface strain patterns in cementless femoral arthroplasty.
A hypothesis associated with applications of contemporary cementless pressfit femoral stem designs is that stems which uniformly fit the proximal medullary canal of the femur will result in load transmission patterns which approximate those of a normal femur. The objective of this study was to examine biomechanical variables such as implant/bone fit and the associated load transmission patterns of the proximal femur before and after cementless femoral arthroplasty utilizing the technique of reflection photoelasticity. Harris-Galante (Zimmer), S-ROM (Joint Medical Products), and INFINITY prostheses were implanted in cadaveric femora and subjected to conditions simulating single-limb stance loading. The bone/implant constructs were later transversely sectioned and fit was analyzed. Insertion and subsequent loading of both prothesis types resulted in a large decrease in strain in the medial calcar of each intact control. Visual examination of the Harris-Galante prosthesis under polarized light revealed patchy, localized areas of high strain along the proximal region. In contrast, the modular prostheses displayed more uniform and diffuse strain profiles with minimal regions of localized strain. In all cases, the surface strain patterns produced by cementless femoral arthroplasty correlated with the pattern and degree of implant/bone fit.


An adaptive resource-allocating network for automated detection, segmentation, and classification of breast cancer nuclei topic area: image processing and recognition.
This paper presents a unified image analysis approach for automated detection, segmentation, and classification of breast cancer nuclei using a neural network, which learns to cluster shapes and to classify nuclei. The proposed neural network is incrementally grown by creating a new cluster whenever a previously unseen shape is presented. Each hidden node represents a cluster used as a template to provide faster and more accurate nuclei detection and segmentation. Online learning gives the system improved performance with continued use. The effectiveness of the resulting system is demonstrated on a task of cytological image analysis, with classification of individual nuclei used to diagnose the sample. This demonstrates the potential effectiveness of such a system on diagnostic tasks that require the classification of individual cells.


Substrate turnover by transporters curtails synaptic glutamate transients.
Although inhibitors of glutamate transport prolong synaptic currents at many glutamate synapses, the cause of the current prolongation is unclear. Transport inhibitors may prolong synaptic currents by simply interfering with synaptic glutamate binding to transporters, by inhibiting substrate translocation, or by promoting accumulation of ambient glutamate, which may act cooperatively at receptors with synaptic glutamate. We show that reversal of the membrane potential of astrocytes surrounding the synapse prolongs synaptic currents but does not decrease the apparent affinity of transporters or significantly alter glutamate-dependent kinetics of macroscopic transporter currents in excised membrane patches. Positive membrane potentials do not affect binding of a nontransported glutamate analog, nor do positive membrane potentials alter the number of transporters available to bind analog. We also test the hypothesis that glutamate accumulation during uptake inhibition by transporter substrates is the direct cause of synaptic current prolongations. Transporter substrates elevate ambient glutamate near synapses by fostering reverse transport of endogenous glutamate. However, increases in ambient glutamate cannot account for the prolongations of synaptic currents, because a nonsubstrate transport inhibitor does not foster reverse uptake yet it prolongs synaptic currents. Moreover, exogenous glutamate does not mimic synaptic current prolongations induced by substrate inhibitors. These results provide strong support for a major role of substrate translocation in determining the time course of the glutamate concentration transient at excitatory synapses.


Surgical reconstruction of acquired spastic foot and ankle deformity.
With the aging population and improved methods of emergency transport, the number of surviving stroke and brain injury patients continues to increase. Aggressive rehabilitation of appropriate candidates is justified. In the period of spontaneous recovery, efforts are made to prevent fixed contractures using passive mobilization, splinting, nerve blocks, and electrical stimulation. If deformity persists and the patient is no longer recovering, operative management can help alleviate the functional and hygiene problems associated with these limb deformities.


Survivin-driven and fiber-modified oncolytic adenovirus exhibits potent antitumor activity in established intracranial glioma.
The poor prognosis of patients with malignant gliomas necessitates the development of novel therapies. Virotherapy, using genetically engineered adenovectors that selectively replicate in and kill neoplastic cells, represents one such strategy. In this study, we examined several oncolytic vectors with modified transcriptional and transductional control of viral replication. First, we incorporated the survivin promoter (S) to drive E1A gene expression. We then modified the adenovirus serotype 5 (Ad5) fiber protein via genetic knob switching or incorporation of peptide ligands to target the following glioma-associated receptors: the Ad3 attachment protein, or CD46, alpha(v) beta(3)/alpha(v)beta(5) integrins, or heparan sulfate proteoglycans. The three conditionally replicative adenoviruses, CRAd-S-5/3, CRAd-S-RGD, and CRAd-S-pk7, were then examined in vitro with respect to transduction efficiency and tissue specificity. The most promising virus was then tested in vivo for evidence of tumor growth inhibition. CRAd-S-pk7 provided the highest level of viral replication and tumor oncolysis in glioma cell lines. At the same time, we observed minimal viral replication and toxicity in normal human brain. Injection of CRAd-S-pk7 inhibited xenograft tumor growth by more than 300% (p < 0.001). Sixty-seven percent of treated mice with intracranial tumors were long-term survivors (>110 days; p < 0.005). Analysis of tumor tissue indicated increased adenoviral infectivity, decreased mitotic activity, and enhanced tumor apoptosis. These findings demonstrate the effectiveness of CRAd-S-pk7 and provide the rationale for further development of this novel oncolytic virus for glioma gene therapy.


Hypoxia-inducible factor-1α protects cervical carcinoma cells from apoptosis induced by radiation via modulation of vascular endothelial growth factor and p53 under hypoxia.
The aim of the study was to assess the role of irradiation in the expression of HIF-1a, VEGF, and P53 in human cervical carcinoma cells under a simulated hypoxia environment. The tetrazolium-based colorimetric cellular assay (MTT) and flow cytometry (FCM) were used to detect the growth inhibition rates of HeLa cells in different groups. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to observe gene and protein expression of HIF-1α, VEGF, and P53. The effect of HIF-1α on radioresistance and expression of VEGF and P53 were confirmed with the HIF-1α siRNA in vivo and in vitro. Hypoxic conditions enhanced the radiation resistance dependent on HIF-1α by elevating the expression of VEGF and inhibiting the expression of p53. After transfection of HIF-1α siRNA, MTT assay showed the survival rates were increased in the cells receiving irradiation under hypoxia. The expression of VEGF decreased significantly more than that of cells transfected with sense oligodeoxynucleotides, while an opposite result was found in the expression of P53 protein in the same X-ray dose (p<0.05). In vivo, the radioresistance of HIF-1α was consistent with the results in vitro. In the future, we might inhibit human cervical cancer progression and enhance the radiosensitivity by inhibiting HIF-1α to reduce VEGF and increase P53 expression. The challenge is how to use this information to optimize cancer therapy.


Testicular torsion in undescended testis: A persistent challenge.
To evaluate the management and outcomes of patients who presented with torsion of an undescended testis and review the reported series in the literature. The case records of 13 patients operated for testicular torsion involving undescended testis were retrospectively reviewed. The medical records included age at presentation, medical history, physical examination, operative findings and the results of follow-up. The diagnosis of torsion of undescended testis was made clinically and confirmed by inguinal exploration. In six cases the testis was preserved and orchiopexy was performed, while in seven cases orchidectomy was performed due to testicular gangrene in six patients and testicular tumor discovered peroperatively in one case. Mean duration of symptoms at time of surgery in the orchiopexy group was 6.5 h and in the orchidectomy group was 21.2 h. From six patients treated by orchiopexy, two patients suffered from testicular atrophy at a mean of 24 months. Testicular torsion in undescended testis is still diagnosed with delay which may affect testicular salvage. The importance of examination of external genital organs is highlighted which should be routinely included by emergency physicians in physical examination for abdominal or groin pain.


Assessment of impacts of public health interventions on the SARS epidemic in Beijing in terms of the intervals between its symptom onset, hospital admission, and notification.
To assess the impacts of public health interventions on the outbreak of SARS in Beijing by analyzing the intervals between symptom onset, hospital admission and notification of its cases. Data of SARS cases reported from the Beijing Municipal Centers for Disease Prevention and Control (BCDC) were collected and analyzed by descriptive epidemiology. In the early epidemic period, the intervals between the disease onset and the hospital admission seemed irregular, so was the intervals between the hospital admission and the notification. After the middle ten days of April, the intervals turned out to be more regular, and the disordered situation in terms of the hospital admission and the case notification was gradually brought under control. Public health interventions against SARS has revealed positive impacts on SARS control program in Beijing. The timing and sensitivity of epidemic information reporting systems has been greatly improved in Beijing as a result of successful fight against this disease.


[Physiologic regeneration and functional activity of hepatocytes in normobaric hypoxia].
It was studied the effects of dosed normobaric hypoxia during 14 and 28 days on physiological regeneration and functional activity liver of parenhima fenomenas of adult rats. It was shown that after completion of experiment at rats increase sizes nucleus, the area of cytoplasm decrease, and also is increase the hepatocytes amount on tissue area unit. Concentration albumin increased after 14 days ofnormobaric hypoxia. Activity alanine aminotranferease increased and aspartate aminotransferase activity decreased after 28 days of dosed normobaric hypoxia. Thus our study suggested that normobaric hypoxia stimulante morphological marcers functional action and regenerator liver ability.


A Randomized Trial of Effects of Alcohol on Cytochrome P450 Eicosanoids, Mediators of Inflammation Resolution, and Blood Pressure in Men.
Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress, and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2 -isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs), and specialized pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Normotensive men (n = 22) were randomly allocated to drink RW (375 ml/d) or the equivalent volume of dealcoholized red wine (DRW) or water for 4 weeks in a 12-week, 3-period crossover trial. BP, heart rate, 20-HETE, F2 -isoprostanes, and SPM were measured at baseline, 4, 8, and 12 weeks. Drinking RW increased BP (p < 0.05), plasma and urinary 20-HETE (p < 0.05), plasma F2 -isoprostanes (p < 0.0001), and the SPMs 18-hydroxyeicosapentaenoic acid (18-HEPE) from EPA, and resolvin D1 (RvD1) and 17R-resolvin D1 (17R-RvD1) from DHA (all p < 0.05) compared with DRW and water. EETs and high-sensitivity C-reactive protein were unaffected by RW. Plasma 18-HEPE was positively related to urinary 20-HETE (p < 0.008) only after RW. This study has shown that men consuming moderate-to-high alcohol as RW for 4 weeks had increased BP, 20-HETE, and oxidative stress, as well as specific SPM that resolve inflammation. These paradoxical findings require further studies to determine whether alcohol stimulates different CYP450 enzymes and whether the findings can be replicated in females.


Nanoscale friction and wear of a polymer coated with graphene.
Friction and wear of polymers at the nanoscale is a challenging problem due to the complex viscoelastic properties and structure. Using molecular dynamics simulations, we investigate how a graphene sheet on top of the semicrystalline polymer polyvinyl alcohol affects the friction and wear. Our setup is meant to resemble an AFM experiment with a silicon tip. We have used two different graphene sheets, namely an unstrained, flat sheet, and one that has been crumpled before being deposited on the polymer. The graphene protects the top layer of the polymer from wear and reduces the friction. The unstrained flat graphene is stiffer, and we find that it constrains the polymer chains and reduces the indentation depth.


The health of Australian baby boomers.
The large baby boomer cohort is beginning to reach retirement age. This paper reviews recent Australian literature on baby boomers' health and health behaviours. Databases were searched for peer-reviewed literature and the Internet for online studies and reports. The boomers can expect an increased life span compared to those in later life now. Boomers' health behavioural risks include physical inactivity, low vegetable consumption, obesity and rising medical risk due to increasing prevalence of diabetes. Their health will impact on workforce participation and retirement timing. There is substantial scope for health improvement and consequent quality of life as boomers age. However, little is known about health decision-making, inequalities between social groups and health information sources. Future research can yield a better understanding of the health trajectories of baby boomers in order to plan for health and service needs for an ageing Australia.


[The meaning of ostomy care among nurses: a case study].
This study aimed to identify how nurses working in a hospital interpret ostomy care. The case-study methodology was used. The obtained results originated four categories: the patient needs special care, it is necessary to provide orientation, in order to provide orientation, the nurse needs..., the recognition of difficulties in delivering special care. These categories express that the care given to ostomy patient by the nurses is not appropriate due to the lack of specific knowledge.


Impaired neutrophil functions in patients with leukocytoclastic vasculitis.
Leukocytoclastic vasculitis (LV) is characterized by segmental inflammation of small blood vessels, resulting in ischemic damage to the surrounding tissue. It is considered to be related to a type III hypersensitivity reaction, although the exact etiologic mechanism is not clear. The purpose of this study was to evaluate neutrophil functions in patients with LV in order to understand their role in the pathogenesis of the disease. Neutrophil functions were examined in 25 LV patients. The patients were divided into two groups: Group A consisted of 14 patients with drug-induced LV and Group B consisted of 11 patients where LV was induced by other factors. Both groups of patients showed significantly reduced chemotaxis and phagocytosis. Superoxide generation was significantly lower (P < 0.001) only in neutrophils from patients in Group A: 5.8 +/- 0.5 nmoles O2/10(6) cells/min compared to 9.08 +/- 0.8 nmoles O2/10(6) cells/min in the controls. Preincubation on normal neutrophils with the patients' sera caused an increase in their superoxide generation in accordance with the high IL-8 levels in these sera. Neutrophil functions were significantly impaired in patients with LV. It is likely that factors present in LV plasma may chronically activate neutrophils, so that they become refractory to further stimulation. Our study showed that neutrophil superoxide generation is low only in drug-induced LV; this test may assist in distinguishing such patients from those with LV induced by other causes.


Expression of DNAJA1 in bovine muscles according to developmental age and management factors.
We have recently shown that the expression of the DNAJA1 gene encoding a heat shock protein (Hsp40) is a negative marker of meat tenderness in Charolais bulls. To acquire knowledge on the regulation of DNAJA1 expression, we analysed the abundance of DNAJA1 transcripts and protein during development and according to management factors (e.g. feeding treatments, growth path and stress status) in different bovine muscles during postnatal life. We report here a developmental expression profile for DNAJA1 with decreased levels of transcript and protein during the progression of myogenesis. During postnatal life, we found the highest expression of DNAJA1 in the most oxidative muscles. No effect was detected for dietary treatment (pasture v. maize-based diet), growth path (compensatory growth after a restriction period) or pre-slaughter stress status. Therefore, the genetic background and muscle type could be considered as the main factors regarding the level of DNAJA1. Integration of the knowledge gained from this study should help to predict muscle metabolic properties and the ability of the live animals to give high sensory quality meat.


Nasal Ventilation Mask for Prevention of Upper Airway Obstruction in Patients With Obesity or Obstructive Sleep Apnea.
This project aimed to develop and implement a nasal ventilation mask (NVM) guideline to reduce the incidence of airway obstruction in outpatients undergoing endoscopy procedures. An observational design was used to evaluate implementation of an NVM guideline as the oxygen delivery method for this patient population. An evidence-based guideline for NVM use was developed for patients with obstructive sleep apnea (OSA) and/or an elevated body mass index (BMI) above 35 kg/m² undergoing esophagogastroduodenoscopy and/or colonoscopy procedures at an outpatient endoscopy clinic. Patients receiving moderate or deep sedation for esophagogastroduodenoscopy, colonoscopy, or both procedures who had a BMI of at least 35 kg/m² and/or an OSA diagnosis were observed for oxygen desaturation, airway maneuvers, and use of airway adjuncts. Intraoperatively, the group of patients who wore an NVM compared with the group that did not wear an NVM had 3 times greater chance of having at least one occurrence of an oxygen saturation less than or equal to 90% and almost 4 times greater chance of having an oxygen desaturation 5% or greater of baseline oxygen saturation. The NVM offers supportive ventilation and the ability to provide positive pressure assistive breaths, both of which are beneficial to the increasingly obese population.


Congestive heart failure associated with hyperthyroidism in cats.
Hyperthyroidism was diagnosed in 4 cats with congestive heart failure. Dyspnea and anorexia were observed in 3 of the 4 cats. In each cat, a holosystolic left and/or right apical heart murmur was auscultated. In 3 cats, a prominent extra heart sound (gallop rhythm) was auscultated. All cats had a palpably large thyroid lobe(s) and weight loss. The laboratory and ECG changes were similar to those reported for feline hyperthyroidism. Moderate-to-severe pleural effusion and cardiomegaly were detected via radiography in all cats. Some cats had radiographic signs of pulmonary venous engorgement and pulmonary edema. Echocardiography revealed cardiac dilatation and low left ventricular shortening fraction (wall motion) in all cats. Three cats responded initially to cardiac drugs and propylthiouracil or thyroidectomy. One of these died later, presumably from an adverse reaction to propylthiouracil, and the others died from recurrent congestive heart failure (1) or postoperative cardiac arrest (1). One cat did not respond to treatment, and died 2 days after diagnosis.


Phenotypic expression of the Pseudomonas syringae pv. syringae 61 hrp/hrm gene cluster in Escherichia coli MC4100 requires a functional porin.
Plants, in general, appear to be able to detect the presence of incompatible Pseudomonas syringae strains by a hypothetical cell-cell recognition process to initiate inducible defense mechanisms that contribute to disease resistance. A 25-kb hrp/hrm gene cluster isolated from P. syringae pv. syringae 61(pHIR11) enables Escherichia coli to elicit a hypersensitive response (HR), a plant response generally considered to be a manifestation of recognition and resistance. To identify the nature of the HR-eliciting signal produced by E. coli cells carrying pHIR11, bacterial surface features were surveyed by immunological and biochemical procedures. No immunoreactive epitopes or outer membrane proteins were detected that were associated with expression of the P. syringae pv. syringae 61 hrp/hrm cluster in E. coli MC4100. Phenotypic expression of the P. syringae pv. syringae 61 hrp/hrm cluster in E. coli MC4100, however, was found to be dependent upon ompC and ompF, which control outer membrane permeability to hydrophilic solutes. The results suggest that deployment of the HR-eliciting signal occurs via outer membrane porins and imply that a low-molecular-weight, hydrophilic factor mediates signal exchange between the bacterium and the responding plant cell.


Gender differences in rates of depression, PTSD, pain, obesity, and military sexual trauma among Connecticut War Veterans of Iraq and Afghanistan.
The current wars in Iraq and Afghanistan have led to an increasing number of female veterans seeking medical and mental healthcare in the Department of Veterans Affairs (VA) healthcare system. To better understand gender differences in healthcare needs among recently returned veterans, we examined the prevalence of positive screenings for depression, posttraumatic stress disorder (PTSD), military sexual trauma (MST), obesity, and chronic pain among female and male veterans of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) receiving care at the VA Connecticut Healthcare System. We performed a retrospective, cross-sectional data analysis of OEF/OIF veterans at VA Connecticut who received services in either Primary Care or the Women's Health Clinic between 2001 and 2006. In this study, 1129 electronic medical records (1032 men, 197 women) were examined. Female veterans were more likely to screen positive for MST (14% vs. 1%, p < 0.001) and depression (48% vs. 39%, p = 0.01) and less likely to screen positive for PTSD (21% vs. 33%, p = 0.002). There was no significant gender difference in clinically significant pain scores. Men were more likely than women to have body mass index (BMI) >30 kg/m(2) (21% vs. 13%, p = 0.008). These results suggest that important gender differences exist in the prevalence of positive screenings for MST, depression, obesity, and PTSD. As the VA continues to review and improve its services for women veterans, clinicians, researchers, and senior leaders should consider innovative ways to ensure that female veterans receive the health services they need within the VA system.


Different nitrogen sources modulate activity but not expression of glutamine synthetase in arbuscular mycorrhizal fungi.
Glutamine synthetase (GS) is a central enzyme of nitrogen metabolism that allows assimilation of nitrogen and biosynthesis of glutamine. We isolated the cDNA encoding GS from two arbuscular mycorrhizal fungi, Glomus mosseae (GmGln1) and Glomus intraradices (GiGln1). The deduced protein orthologues have a high degree of similarity (92%) with each other as well as with GSs from other fungi. GmGln1 was constitutively expressed during all stages of the fungal life cycle, i.e., spore germination, intraradical and extraradical mycelium. Feeding experiments with different nitrogen sources did not induce any change in the mRNA level of both genes independent of the symbiotic status of the fungus. However, GS activity of extraradical hypahe in G. intraradices was considerably modulated in response to different nitrogen sources. Thus, in a N re-supplementation time-course experiment, GS activity responded quickly to addition of nitrate, ammonium or glutamine. Re-feeding with ammonium produced a general increase in GS activity when compared with hyphae grown in nitrate as a sole N source.


Intracellular Flow Cytometric Measurement of Extracellular Matrix Components in Porcine Intervertebral Disc Cells.
The objective of this study was to develop and demonstrate the utility of a novel method of evaluating intracellular levels of extracellular matrix (ECM) components in intervertebral disc (IVD) cells using flow cytometry. By using this method, this study discriminated between cell populations in porcine IVD and examined the response of IVD cells to monolayer cultures, a traditional method of cell expansion, by measuring phenotypic attributes of ECM component production. It was found that monolayer cultures affected collagen production of IVD cells while there were differences in collagen type II production between the cells isolated from the annulus fibrosus (AF) and nucleus pulposus (NP) regions of IVD. Size distributions of fresh and cultured cells were also presented while the relationships between cell size and intracellular collagen level revealed heterogeneous cell populations in AF and NP regions. Furthermore, this study showed that the intracellular collagen signals of IVD cells were significantly enhanced by the treatments of Brefeldin-A and ascorbic acid. This suggests that Brefeldin-A and ascorbic acid could be used to increase the sensitivity of flow cytometric analysis on intracellular collagen levels by maximizing collagen accumulation inside cells. Since a unique feature of the flow cytometric screening tool is the ability to discriminate between various cell populations in a single sample, the flow cytometric method developed in this study may have the potential to identify specific collagen-producing cell populations from tissues or cell cultures.


Axillary basal cell carcinoma.
Basal cell carcinoma (BCC) rarely occurs in the axilla. Only 18 cases have been reported in the world literature. To report our institution's 11-year experience with axillary BCC. A review of patient charts and biopsy specimens is given. We report 14 patients with 15 axillary BCCs. The average patient age was 65.6. The average lesion size was 10.8 mm. Nine patients had a personal history of skin cancer at sun-exposed sites. One patient had basal cell nevus syndrome. A history of ionizing radiation and severe sunburn involving the axilla was each seen in separate patients. No other predisposing factors for developing BCC were identified, such as immune suppression or a history of other malignancies. Histologic subtypes of all tumors were considered less aggressive, and only one tumor recurred. Axillary BCC is rare. Factors other than ultraviolet radiation likely contribute to the development of BCC, especially at sun-protected sites. Performing a periodic and complete cutaneous examination that includes sun-protected sites is important, especially in patients who have a history of skin cancer.


Staff Knowledge, Attitudes, and Practices Regarding Nicotine Dependence Differ by Setting.
This study examined smoking-related knowledge, beliefs, self-efficacy, smoking cessation practices, and barriers to providing smoking cessation services in a workforce sample. The 11 participating clinics (N=335 staff) included substance abuse treatment and HIV care clinics categorized into three types: Veterans Affairs Medical Center (VAMC) clinics, hospital-based clinics, and community-based clinics. Staff in both VAMC and hospital-based settings shared characteristics that may predict smoking-related knowledge, beliefs, and practices (higher education level, low smoking rates, fewer staff in recovery, and location in hospital-affiliated environments where there was greater emphasis on physical health). However, staff in VAMC settings outperformed those in both hospital-based and community-based clinic settings on measures of smoking-related knowledge, beliefs, self-efficacy, and practices. Well-developed procedures to support VAMC clinicians in addressing smoking may account for these findings. Findings suggest that both reductions in staff smoking, and development and implementation of smoking policy are needed to support staff in better addressing nicotine dependence in community-based treatment settings.


DEVELOPMENT AND VALIDATION OF A NEW LAPAROSCOPIC ENDOTRAINER FOR NEONATAL SURGERY AND REDUCED SPACES.
Pediatric laparoscopy box with sliding tray. Pediatric procedures have the difficulty of being performed in reduced spaces. Training in reduced spaces has proven to be different in complexity compared to adult laparoscopic endotrainers. To develop and validate a new neonatal/reduced-space endotrainer. The simulator was tested and assessed by users with different skill levels and experience in laparoscopic pediatric surgery through an 8-item questionnaire. Construct validity was determined by evaluating the performance of each subject on nine exercises. A 10.5 x 10 x 18 cm acrylic simulator was created, with an internal working surface of 9 x 9 cm. An HD camera was incorporated, with a 0-180° range of movement. All exercises of a Basic Laparoscopic Training Program were adapted on a scale of 1:0.5 to fit in. From 49 participants, 42 (85.71%) answered the survey; 80.5% considered that the simulator reproduces similar conditions to procedures performed in children under one year of age; 61.1% thought that the simulator represents a difficulty identical to procedures performed in newborns; 73.7% considered that the neonatal simulator is more complicated than the adult simulator. Experts showed significantly better performance in all proposed exercises. The simulator has a high-quality image and design that allows training with basic tasks. The endotrainer permitted to discriminate between these different skill levels and was well evaluated by users with diverse surgical experience.


[Lysosomal cationic proteins in neutrophilic granulocytes during phagocytosis and inflammation].
Literature and experimental data are reviewed on functional properties of cation proteins in neutrophil granulocytes under conditions of phagocytosis and inflammation. These proteins are not only effective antimicrobial agents but they regulate a lot of protective-adaptational reactions responsible for development of human and animal unspecific resistance.


[Evaluation of the functional activity of peritoneal macrophages using the tetrazolium test].
The redox activity of peritoneal macrophages has been evaluated in the modified NBT test using tetranitro blue tetrazolium. This method permits the calculation of the total amount of peritoneal macrophages and the determination of their glass adherence per cent and their cytochemical activity value. The advantages of this method over the study of the phagocytic activity by means of phage T2 is shown.


[The presence and vector role of Culex bitaeniorhynchus in New Caledonia].
Culex bitaeniorhynchus, reported from New Caledonia after a single collection of larvae in Noumea in 1952, has been found in two other localities, on the south-west and on the north-east coasts. The morphological features show some differences between the local population and the forms from the Oriental Region. Adults have been caught during the hot and rainy season, by light traps mainly. The females have been very rarely collected on human bait. Though found naturally infected by dengue 4 virus, that species is not likely to have an epidemiological importance in New Caledonia. It seems doubtful that it has been imported recently.


Experimental toxoplasmosis in broiler chicks.
To evaluate chicken toxoplasmosis both as an economic and a public health subject, 84 broiler chicks of a commercial strain, 30 days old, were distributed into seven groups of 12 birds (three replications of four chicks) experimentally infected with three developing T. gondii stages of the P strain as follows: tachyzoites, intravenous (two groups: 5.0 x 10(5) and 5.0 x 10(6)), cysts, per os (two groups: 1.0 x 10(2) and 1.0 x 10(3)) and oocysts, per os (three groups: 5.0 x 10(2), 5.0 x 10(3) and 5.0 x 10(4)). Twelve chicks received only a placebo (control group). During the next 30 days the following parameters were estimated: productivity (weight gain and feed conversion), clinical signs, including rectal temperature and parasitemia (bioassay). No clinical signs suggesting toxoplasmosis were seen and no statistical differences on productivity standards were found in comparison between inoculated and control chicks. However, fowls inoculated with tachyzoites and oocysts occasionally showed hyperthermia. Some haematological changes were detected in fowls inoculated with T. gondii. Anatomo-histopathological changes were not observed. From 14 parasitemias detected, 35.7% appeared on the 5th day after inoculation and 57.1% of them resulted from oocysts inoculation. After 30-35 days all birds were slaughtered: fragments from 12 organs or tissues from each of them were subjected to artificial peptic digestion and after that injected into T. gondii antibody-free mice (IIFR). T. gondii was detected in brain (12), pancreas (five), spleen (five), retina (five), kidney (two), heart (four), proventriculus (three), liver (two), intestine (two), lung (one), and skeletal muscle (one). Similar to observations with parasitemia, from 42 T. gondii isolations, 59.5% came from chicks which had received oocysts. It can thus be inferred that the developing form, expelled by cats, is the most important for T. gondii chicken infection and that brain is the most infected organ in birds. Attention must be paid to the potential importance of chicken meat in public health, since T. gondii was isolated from skeletal and heart muscles.


Percutaneous endoscopic gastrostomy site metastases in head and neck cancer: use of FDG PET-CT.
To retrospectively evaluate the utility of positron emission tomography-computed tomography (PETCT) in the diagnosis of percutaneous endoscopic gastroscopy (PEG) site metastases in head and neck cancer. From the database of 250 patients of head and neck cancer who were referred for PET-CT over 2 years (from January 2005 to January 2007), 6 patients who had PEG tube placement were considered for the study. Imaging was performed on a GE Discovery ST PET-CT system after intravenous injection of 370 MBq (10 mCi) of < sup > 18 < /sup > F-fluorodeoxyglucose (FDG). Intense FDG uptake with an associated soft tissue mass was seen at the PEG site in 3 patients and mild uptake was seen in 2 patients. Biopsy revealed PEG site metastases in 2 patients, abscess in 1 patient, and granulation tissue in 1 patient. Intense uptake with an associated soft tissue mass suggested the diagnosis of metastasis. Stranding of the peristomal fat seen on the CT component of the PET-CT indicated an infective/inflammatory pathology. PET-CT findings showed local recurrence in 3 patients and disseminated metastases (excluding the PEG site) in 1 patient. The functional information provided by PET combined with the morphologic detail of CT can improve characterizing of the stoma site abnormality and help in distinguishing recurrence from infective/inflammatory changes. Whole body combined PET-CT is a useful modality for evaluating gastrostomy site metastases and for detecting coexisting local recurrences and distant metastases in head and neck cancer patients. In addition it can detect early asymptomatic recurrences at the gastrostomy site.


Design and application of a novel high precision and low cost electronic tachogenerator for sensor-based brushless direct current motor drivers.
This study presents a precise speed control method for Brushless Direct Current (BLDC) Motors using an electronic tachogenerator (ETg) instead of an electro-mechanical tachogenerator. Most commonly used three-phase BLDC motors have three position sensors for rotor position data to provide commutation among stator windings. Aforementioned position sensors are usually Hall-effect sensors delivering binary-high and binary-low data as long as the motor rotates. These binary sets from three Hall-effect sensors can be used as an analogue rotor speed signal for closed loop applications. Each position sensor signal is apart from 120 electrical degrees. By using an electronic circuitry, a combination of position sensor signals is converted to the analogue signal providing an input to a PI speed controller. To implement this, a frequency to voltage converter has been used in this study. Then, the analogue speed signal has been evaluated as rotor speed data in comparison with the reference speed. So, an ETg system has been successfully achieved in place of an electro-mechanical tachogenerator for BLDC motor speed control. The proposed ETg has been tested under various speed conditions on an experimental setup. Employed tests and obtained results show that the proposed low-cost speed feedback sub-system can be effectively used in BLDC motor drive systems. Through the proved method and designed sub-system, a new motor controller chip with a speed feedback capability has been aimed.


Writing treatment for severe aphasia: who benefits?
Writing treatment that involved repeated copying and recall of target words was implemented with 8 individuals with severe aphasia in order to discern the best candidates for the treatment. Four of the 8 participants had strong positive responses to the copy and recall treatment (CART), relearning spellings for 15 targeted words during 10 to 12 weeks of treatment and up to 5 additional words during a month-long homework-based program. Of the 4 other participants, 3 learned the spellings of some target words but failed to reach criterion, and 1 had a poor treatment outcome. Insights regarding possible factors that limited success were gained by examination of individual responses to treatment as well as performance on the pretreatment assessments of semantic, phonological, and orthographic processes. Among the factors associated with success were (a) consistent, accurate completion of daily homework, (b) a relatively preserved semantic system, (c) the ability to discern words from nonwords, and (d) adequately preserved nonverbal visual problem-solving skills. Aphasia severity and minimal pretreatment spelling abilities did not necessarily limit the response to treatment. Participants with positive treatment outcomes demonstrated improved spelling of target words following repeated copying within a single treatment session, and accurately completed daily writing homework. Thus, pretreatment assessment and stimulability within initial treatment sessions provided indications of likely outcome.


Understanding Aboriginal Models of Selfhood: The National Empowerment Project's Cultural, Social, and Emotional Wellbeing Program in Western Australia.
Culturally safe and responsive interventions that acknowledge Aboriginal models of selfhood are needed. Such interventions empower Aboriginal peoples and communities by increasing self-determination over individual and community social and emotional wellbeing (SEWB). In response to this need, the National Empowerment Project developed the Cultural, Social, and Emotional Wellbeing Program (CSEWB). The CSEWB aims to strengthen SEWB and cultural identity and subsequently reduce psychological distress in Aboriginal peoples. An Aboriginal Participatory Action Research approach ensured community ownership and engagement. Seven research questions and a culturally modified adaption of the Most Significant Change technique informed a thematic analysis of the evaluation content. Aboriginal adults (n = 49; 53% ≥50 years, 66% female, 34% male) from three Western Australian urban communities participated in the program evaluation workshops. Participants reported the benefits of enhanced SEWB and reduced psychological distress. This research reaffirms the need for culturally safe programs that acknowledge social determinants of health and are guided by the SEWB framework. Long-term commitment from the government is needed to support such programs.


Predictive factors for time to remission and recurrence in patients treated for acute mania: health outcomes of manic episodes (HOME) study.
To determine the time to remission and recurrence in patients treated for acute mania and the predictive factors associated with these outcomes. This observational study, conducted in Turkey from April 2003 to January 2005, included patients with a DSM-IV diagnosis of bipolar I disorder, acute manic or mixed episode who were eligible to have an oral medication initiated or changed for the treatment of the episode. The patients were followed-up for 12 months. A total of 584 patients (mean ± SD age = 33.9 ± 11.2, 55.2% outpatients) were enrolled in 53 centers. Eighty-five percent of patients had a manic episode at baseline, with a mean ± SD duration of 21.6 ± 24.4 days. The baseline mean ± SD Clinical Global Impressions scale for use in bipolar disorder and Young Mania Rating Scale (YMRS) scores were 4.9 ± 0.9 (median = 5.0) and 33.2 ± 9.3 (median = 33), respectively. 539 patients achieved remission and, of those, 141 patients had recurrence. One-year remission and recurrence rates were 99.0% and 35.7%, respectively. Mean ± SD times to remission and recurrence in descriptive statistics were 80.9 ± 73.8 (median = 50) and 159.0 ± 95.5 (median = 156) days, respectively. In Cox regression analysis, psychiatric comorbidities (p = .048), a higher YMRS score (p < .001), and a higher number of previous depressive episodes (p = .009) were statistically significant predictors of a longer time to reach remission. Index episodes of longer duration (p = .033) and mixed type (p = 0.49) were significant predictors of a shorter time to recurrence. Confounding factors like concomitant treatment, comorbidities, and lack of blinding and randomization were other limitations. Predictors for a longer time to remission were psychiatric comorbidities, a higher YMRS score, and a higher number of previous depressive episodes. Predictors for a shorter time to recurrence were episodes of longer duration and mixed type.


Observations and management of fractures of the proximal phalanx in young Thoroughbreds.
A retrospective study of 119 cases of fracture of the proximal phalanx is described. The short incomplete sagittal fracture (split pastern) was most common and carried a good prognosis for a return to racing following conservative treatment. Longer incomplete fractures also had a good prognosis but complete fractures, either through the lateral cortex of the proximal phalanx or through the bone into the proximal interphalangeal joint, required internal fixation. Careful assessment of these and comminuted fractures was essential before surgery was undertaken. Most comminuted fractures were treated with a view to the animal retiring to stud rather than racing again. Humane destruction was considered to be justifiable for such fractures in colts or geldings of no stud value or if the fracture was severely comminuted.


Adrenergic modulation of choroidal blood flow in the rabbit.
To determine whether the choroidal pressure-flow is altered by the alpha-adrenergic antagonist, phentolamine, or the beta-adrenergic antagonist, propranolol. In two groups of pentobarbital- anesthetized rabbits, the choroidal pressure-flow relationships were determined by raising the intraocular pressure (IOP) at mean arterial pressure (MAP) of 50, 60, 70, and 80 mm Hg before and after phentolamine (0.5 mg/kg, intravenously, n=7) and propranolol (0.25 mg/kg intravenously, n=7) administration. Hydraulic occluders on the thoracic aorta and inferior vena cava were used to control MAP, which was measured in the central ear artery. The eye was cannulated with two 23-gauge needles, one to manipulate the ocular volume and the other to measure the IOP. Choroidal blood flow was measured by laser Doppler flowmetry with a probe positioned over the posterior retina. The protocol consisted of setting the MAP, then infusing saline into the eye at 30 microliters/minute until the IOP increased from baseline to 100 mm Hg. At the MAP of 70 mm Hg, alpha-adrenergic blockade caused an upward shift in the choroidal pressure-flow relationship; beta-blockade shifted the relationship downward. In the pentobarbital-anesthetized rabbit, alpha- and beta- adrenergic blockade cause choroidal vasodilation and vasoconstriction, respectively. Results indicate the presence of alpha- and beta-adrenergic receptors in the rabbit choroid and a tonic level of adrenergic vascular tone in this preparation.


An overview of delayed passive eruption.
The condition of delayed or altered passive eruption exists in adults when the gingival unit remains positioned on the convex prominence of the enamel rather than at or in proximity to the cementoenamel junction. Treatment protocol is based on periodontal, esthetic, and prosthetic considerations. In addition, the gingival/osseous relationship becomes important for proper diagnosis and treatment. The purpose of this article is to increase awareness of the pathognomonic signs and symptoms of delayed passive eruption so that appropriate treatment can be rendered.


[Examination of the postoperative change of pedicled pericardial fat pad for reinforcement of bronchial sutures by computed tomography].
A pedicled pericardial fat pad (PPFP) is often used in pulmonary resection to reinforce bronchial sutures. Here, we assessed the significance of PPFP by serial chest computed tomography (CT). Ten cases in which bronchial stump were covered with a PPFP in the past 6 years were reviewed. The procedures were pneumonectomy (3), lobectomy (6), and a segmentectomy. According to the CT value evaluated serially PPFP was recognized as fat tissue until 1~2 postoperative months. No cases of bronchopleural fistulae was encountered in this series. The coverage of the sutures with the PPFP was thought to contribute to the prevention of bronchial fistula by staying around bronchial stump for at least 1 to 2 months.


Age estimation in the combined long bones and ribs by histomorphometry: Past, present, and future.
Numerous age estimation methods in unidentified bone have been a long time developing for application in forensic anthropology. The histomorphometric technique is one of the alternative methods that relied upon the evaluation of the cortical bone microstructure over the lifespan as a result of the remodeling process in bone. Remodeling is a sophisticated event occurring from the coupled function of bone formation and resorption cells for maintaining mineral homeostasis and repairment of microdamage in bone tissue. Products derived from remodeling are primary changes in the osteon or haversian system in various regions in the cortical bone, including periosteum, endosteum, and trabecular bone. Throughout life, bone remodeling rate with osteon alteration can be predictable. In the forensic field, histological methods are getting more attention due to the unavailability of macroscopic methods. Histomorphometry approach can be accomplished in fragmentary or incomplete bone remains indicating the limited use of gross morphological methods. In addition, the microscopic methods can aid to increase the more accuracy of analyses and diminish the biased subjective assessment for determining age. Most histomorphometry method utilizes a cross-section of the midshaft of the long bones including the mandible, rib, and clavicle. This review provides the basic knowledge of bone biology and anatomy, several age-estimating methods of histology, and crucial factors for age methods. Studies regarding overall age determination methods from the past until now contribute to obtaining more benefits for developing methods of histomorphometry using human bone in forensic identification.


Bacterial degradation of diphenylmethane, a DDT model substrate.
A strain of Hydrogenomonas was isolated by elective culture in a solution with diphenylmethane, an analogue of DDT, as the sole carbon source. Constitutive enzymes effected the oxidation and fission of one of the benzene rings of diphenylmethane, and phenylacetic acid was found as a major degradation product. Small amounts of phenylglyoxylic and benzoic acids were also generated from diphenylmethane by the bacterium. Phenylacetic acid, which contains the second benzene ring of diphenylmethane, was metabolized by inducible enzymes.


The Cambridge glioma trial of misonidazole and radiation therapy with associated pharmacokinetic studies.
Fifty-five patients with grade 3 and 4 supratentorial astrocytomas, were randomized into a three-limb study. Patients in group 1 received 5656 rads in 28 fractions in 5 1/2 weeks (202 rads daily). Group 2 received 4352 rads in 12 unequal fractions in 4 weeks (294 rads each Monday and Wednesday and 500 rads on Fridays). Group 3 received the same radiation as in group 2 but were given 3 g/m2 oral misonidazole 4 hours before the 500-rad fraction, i.e., once a week for 4 weeks. The radiation dosage in each group was equal to 1702 ret. At 9 months after the last treatment there were no differences in survival between the treatment groups. No cases of peripheral neuropathy were seen and the plasma misonidazole t1/2 of 8.6 +/- 0.62 (S.D.) hours were low. Investigations into the possible cause of this are presented. It is thought that microsomal enzyme induction by the anticonvulsants phenobarbitone and phenytoin resulted in increased O-demethylation of the misonidazole. Clinical data to confirm this view are presented. Current MRC protocols of misonidazole studies on gliomas and carcinomas of the cervix and head and neck are summarized.


Optimization of Titanium Dental Mesh Surfaces for Biological Sealing and Prevention of Bacterial Colonization.
Titanium dental meshes have a wide application in order to ensure the retention of calcium phosphate-based biomaterials to regenerate bone tissue. These meshes are temporary and must grow a soft tissue to prevent bacterial colonization and provide stability. In this work, we aimed to optimize the roughness of the meshes to obtain a good biological seal while maintaining a behavior that did not favor bacterial colonization. To this end, six types of surfaces were studied: machined as a control, polished, sandblasted with three different alumina sizes and sintered. The roughness, contact angles and biological behavior of the samples using fibroblast cultures at 7, 24 and 72 h were determined as well as cytotoxicity studies. Cultures of two very common bacterial strains in the oral cavity were also carried out: Streptococcus sanguinis and Lactobacillus salivarius. The results showed that the samples treated with alumina particles by sandblasting at 200 micrometers were the ones that performed best with fibroblasts and also with the number of bacterial colonies in both strains. According to the results, we see in this treatment a candidate for the surface treatment of dental meshes with an excellent performance.


Stabilization of mitochondrial function by chlorogenic acid protects against kainic acid-induced seizures and neuronal cell death in rats.
The current study investigated the effect of chlorogenic acid, a polyphenolic compound found in numerous plant products, on a kainic acid-induced seizure rat model and its potential mechanism. Rats were administered chlorogenic acid (10 and 50 mg/kg) intraperitoneally for 30 min before kainic acid (15 mg/kg) intraperitoneal administration. Pretreatment with chlorogenic acid decreased the seizure score, increased the latency to onset of the first seizure, and decreased the mortality rate. Chlorogenic acid pretreatment also resulted in a significant reduction in glutamate elevation and neuronal death in the hippocampus of kainic acid-treated rats. In addition, electron microscopy revealed that kainic acid-induced changes in hippocampal mitochondrial structure were prevented by chlorogenic acid pretreatment. Additionally, the levels of mitochondrial function-related proteins, including sirtuin 3, Complex I, glutamate dehydrogenase 1 and ATP synthase, were increased, and the level of the mitochondrial damage marker cytochrome C was decreased in the hippocampus of chlorogenic acid/kainic acid rats. Furthermore, the expression of mitochondrial biogenesis-related proteins [AMP-activated protein kinase (AMPK), sirtuin1, and peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α)] and mitophagy-related proteins [phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), Parkin, and microtubule-associated protein 1 light chain 3 (LC3)] was decreased in the hippocampus of kainic acid-treated rats, which was reversed by chlorogenic acid pretreatment. These observations reveal the marked neuroprotective potential of chlorogenic acid against kainic acid-induced neurotoxicity and seizures through prevention of glutamate increase and preservation of AMPK/sirtuin 1/PGC-1α-mediated mitochondrial biogenesis and PINK1/Parkin-induced mitophagy to maintain adequate mitochondrial homeostasis and function.


Transgenic mice overexpressing the growth-hormone-releasing hormone gene have high concentrations of tachykinins in the anterior pituitary gland.
According to recent reports, substance P (SP) is localized in the anterior pituitary gland within subsets of thyrotropes and somatotropes, although earlier electron-microscopic studies described the presence of this tachykinin in mammotropes and gonadotropes. Transgenic mice overexpressing the growth-hormone-releasing hormone (GHRH) gene have markedly enlarged pituitary glands, due to hyperstimulation of the somatotropes. Therefore, we speculated that if somatotropes are able to synthesize tachykinins, these peptides should be greatly increased in the anterior pituitary of transgenic GHRH mice. We found that, in accordance with our working hypothesis, both SP and neurokinin A (NKA) were markedly increased in the anterior pituitary gland of male and female transgenic mice, compared with their respective normal controls. In male transgenic mice, NKA was 13.6- and SP 20.2-fold higher than in the anterior pituitary from normal mice. In female transgenic mice, NKA was 40- and SP 100-fold higher than in the anterior pituitary from normal female mice. In male transgenic mice, NKA and neuropeptide K (NPK) contents in the anterior pituitary showed no significant changes between 26 and 50 days of age but significantly increased between 50 days and 5 months of age. The concentration of NKA in the anterior pituitary did not show significant differences between 26 days and 5 months of age, but NPK concentrations in the anterior pituitary significantly decreased with age. In female transgenic mice, NKA content and concentration in the anterior pituitary increased after 35 days of age, but NPK concentrations significantly decreased after 26 days of age. Triiodothyronine markedly decreased anterior pituitary tachykinins, but ovariectomy and estrogen administration failed to significantly affect tachykinin concentrations in the anterior pituitary of transgenic mice. Tachykinin immunostaining was detected in some somatotropes, but tachykinins were also present in cells that were not GH positive. These findings indicate that hyperstimulated somatotropes contain increased stores of tachykinins and that these cells are a source of tachykinins in the anterior pituitary. Tachykinin stores in the anterior pituitary of transgenic mice were affected by thyroid hormones but seem to be insensitive to estrogens. The GHRH transgenic mice may be an interesting model to study the regulation of tachykinin stores in the anterior pituitary gland.


Scalable, sustainable cost-effective surgical care: a model for safety and quality in the developing world, part III: impact and sustainability.
The Guwahati Comprehensive Cleft Care Center (GCCCC) utilizes a high-volume, subspecialized institution to provide safe, quality, and comprehensive and cost-effective surgical care to a highly vulnerable patient population. The GCCCC utilized a diagonal model of surgical care delivery, with vertical inputs of mission-based care transitioning to investments in infrastructure and human capital to create a sustainable, local care delivery system. Over the first 2.5 years of service (May 2011-November 2013), the GCCCC made significant advances in numerous areas. Progress was meticulously documented to evaluate performance and provide transparency to stakeholders including donors, government officials, medical oversight bodies, employees, and patients. During this time period, the GCCCC provided free operations to 7,034 patients, with improved safety, outcomes, and multidisciplinary services while dramatically decreasing costs and increasing investments in the local community. The center has become a regional referral cleft center, and governments of surrounding states have contracted the GCCCC to provide care for their citizens with cleft lip and cleft palate. Additional regional and global impact is anticipated through continued investments into education and training, comprehensive services, and research and outcomes. The success of this public private partnership demonstrates the value of this model of surgical care in the developing world, and offers a blueprint for reproduction. The GCCCC experience has been consistent with previous studies demonstrating a positive volume-outcomes relationship, and provides evidence for the value of the specialty hospital model for surgical delivery in the developing world.


From Focused Thought to Reveries: A Memory System for a Conscious Robot.
We introduce a memory model for robots that can account for many aspects of an inner world, ranging from object permanence, episodic memory, and planning to imagination and reveries. It is modeled after neurophysiological data and includes parts of the cerebral cortex together with models of arousal systems that are relevant for consciousness. The three central components are an identification network, a localization network, and a working memory network. Attention serves as the interface between the inner and the external world. It directs the flow of information from sensory organs to memory, as well as controlling top-down influences on perception. It also compares external sensations to internal top-down expectations. The model is tested in a number of computer simulations that illustrate how it can operate as a component in various cognitive tasks including perception, the A-not-B test, delayed matching to sample, episodic recall, and vicarious trial and error.


Severe mechanical dyssynchrony causes regional hibernation-like changes in pigs with nonischemic heart failure.
Sustained left ventricular (LV) dyssynchrony can lead to heart failure (HF) in the absence of coronary artery stenosis. We tested whether myocardial hibernation underlies the LV functional impairment caused by high-frequency pacing, an established model of nonischemic dilated cardiomyopathy. Regional LV contractile and perfusion reserve were assessed by magnetic resonance imaging, respectively, as end-systolic wall thickening (LVESWT) and myocardial perfusion reserve index (MPRI) at rest and during low-dose dobutamine stress (LDDS, 10 microg.kg.min intravenously for 10minutes) in failing minipigs (n=8). LV tissue was analyzed for glycogen deposits and other molecular hallmarks of hibernation. LDDS caused a marked increase in LVESWT (27+/-2.98 vs. 7.15+/-3 %, P < .05) and MPRI (2.1+/-0.5 vs. 1.3+/-0.3 P < .05) in the region that was activated first (pacing site) compared with the opposite region. Myocardial glycogen content was markedly increased in the pacing site (P < .05 vs. opposite region). In addition, gene expression of glycogen phosphorylase was reduced in pacing site compared with opposite regions (0.71+/-0.1 vs. 1.03+/-0.3, P < .05), whereas that of hexokinase type II was globally reduced by 83%. The combination of high heart rate and sustained dyssynchronous LV contraction causes asymmetrical myocardial hibernation, in absence of coronary artery stenosis.


Multifocal early gastric cancer in a patient with autoimmune atrophic gastritis and iron deficiency anaemia.
Autoimmune atrophic gastritis (AMAG) is characterised by the presence of parietal cell antibodies (PCA) and occurs in the gastric corpus. Pernicious anaemia (PA) is regarded as the most distinct feature and sequela of AMAG and is associated with the presence of PCA in about 60 - 90 % of cases. AMAG is considered as an independent risk factor for the development of gastric cancer. Interestingly, the risk to progress from metaplasia to neoplasia and ultimately invasive cancer has exclusively been described in patients with PA. However, AMAG can also occur in the absence of PA, sometimes even in association with other haematological manifestations such as iron deficiency anaemia (IDA). This is the first report of a patient with AMAG associated with IDA and the development of multifocal early gastric cancer only three years after initial diagnosis. Furthermore, our patient showed an atypical morphological distribution pattern of atrophic mucosa with involvement of both the gastric corpus and the antrum. H. pylori infection as a cause for the involvement of the antrum could be repeatedly excluded by breath test, histology and serological testing for H. pylori antibodies. In summary, the presence of IDA together with an atypical distribution pattern of AMAG may represent predictors for the individual risk to progress to gastric cancer and should be taken into account in surveillance strategies.


[Enterosorbent SKN in the combined rehabilitative treatment of patients who have had a myocardial infarct].
A study of 34 patients with 2-3 months history of myocardial infarction revealed that 10-day course of treatment with SKN enterosorbent resulted in normalization of lipid peroxidation and several indices of lipid metabolism. These changes were in a part of the patients accompanied by an increase of tolerance to physical load and reduced requirement of the myocardium in oxygen.


Prolonged progressive calcaneal bone loss despite early weightbearing rehabilitation in patients surgically treated for Achilles tendinosis.
We prospectively evaluated areal bone mineral density (BMD) of the calcaneus and calf-muscle strength (concentric and eccentric plantar flexion peak torque in Nm) in 10 recreational athletes (5 males and 5 females), mean age 40.9 years (range 26-55), who were selected to undergo surgical treatment for chronic Achilles tendinosis localized at the 2-6 cm level. Surgery was followed by immobilization in a plaster cast for 2 weeks, followed by flexibility training and slowly progressing strength training and weight-bearing activity. One patient was excluded after week 0 because of a new injury. Seven patients were back to their preinjury activity at the 26-week control, and eight patients at the 52-week control postoperatively. BMD in the calcaneus and calf-muscle strength on the injured and noninjured side was measured preoperatively (week 0) and postoperatively (weeks 2, 6, 16, 26, and 52). There were no significant differences in BMD between the injured and noninjured side at weeks 0, 2, and 6, but at weeks 16, 26, and 52, BMD was significantly (P < 0.05) lower (11.5%, 18.4%, and 16.4%, respectively) in the calcaneus of the injured side. Concentric and eccentric plantar flexion strength were significantly lower on the injured side preoperatively. Eccentric, but not concentric plantar flexion strength had recovered compared with the noninjured side 1 year postoperatively. Calf-muscle strength was not related to bone mass in the calcaneus. As a comparison, we used a group of 11 recreational athletes (10 males and 1 female), with a mean age of 46.1 years (range 28.9-58.5) who had been surgically treated for chronic Achilles tendinosis at the 2-6 cm level 39.5 +/- 11.8 months ago. In this group, there was no significant difference in BMD of the calcaneus between the injured and noninjured side. It seems that there was a delayed and prolonged calcaneal bone loss despite early weightbearing loading in patients surgically treated for chronic Achilles tendinosis at the 2-6 cm level. Around that time, when the Achilles tendon had healed (4-6 months) and the athletes returned to their sports, the calcaneal bone had a relatively low BMD and might possibly be vulnerable to heavy loadings. There were no signs of recovery 1 year postoperatively, but in a comparison group there were no significant side-to-side differences 39.5 months postoperatively.


Differential effects of doxorubicin and docetaxel on nitric oxide production and inducible nitric oxide synthase expression in MCF-7 human breast cancer cells.
Anthracyclines and docetaxel are frequently used agents in the chemotherapy of breast cancer. In this study we examined the role of inducible nitric oxide synthase (iNOS) expression during the cytotoxicity of these drugs in the MCF-7 breast cancer cell line. Cell viability and cytotoxicity were evaluated by the trypan blue dye exclusion method. Apoptosis and necrosis were determined by the acridine orange/ethidium bromide dye method. The percentage of apoptotic cells was significantly higher with doxorubicin. However, total cytotoxic cell numbers were higher in the docetaxel group compared with doxorubicin, with respect to the control. Most of the cells were seen to be necrotic with the dye method. Cell extracts during the apoptotic process were applied to immunoblot by anti-iNOS monoclonal antibodies. While there was an increase in iNOS expression during docetaxel induced-cytotoxicity, a significant decrease in iNOS expression was detected during doxorubicin-induced cytotoxicity. The Griess method was used for detection of nitrate levels. It was compatible with immunoblot results. These data open a window for further studies to understand the mechanism underlining the cytotoxicity of docetaxel and doxorubicin.


Adverse reactions to food in New Zealand children aged 0-5 years.
The aim of this study was to describe parent/caregiver-reported adverse reactions to food in children aged 0-5 years in New Zealand. A cross-sectional survey was undertaken in clinics conducted by the Royal New Zealand Plunket Society, which is the major healthcare provider for New Zealand's Well Child programme. Parents/caregivers of 110 (65%) children participated. Of the 44 children who experienced an adverse reaction to food, only four were clinically evaluated and had undergone diagnostic testing. Two other children were hospitalised following systemic symptoms. Neither was tested for food allergy. 18 (16%) children had physician diagnosed eczema. Within the limitations of this small study, the data indicated adverse reactions to foods are a public health concern in New Zealand and may be under investigated even in children with severe symptoms. These children remain at increased risk of continued morbidity. Based on this preliminary study further research on food allergy in New Zealand is warranted.