Characteristics of medial-lateral postural control while exposed to the external perturbation in step initiation.
Controllability of posture in the medial-lateral direction is critical for balance maintenance, particularly in step initiation. The objective of the current study was to examine the effects of external perturbation and landing orientation on medial-lateral control stability in step initiation. Eleven young healthy participants stood on the force platform and waited for the instruction of taking a step while experiencing a pendulum perturbation applied at the lateral side of the right shoulder. Eight experimental conditions were conducted by two levels of step side (right or left), two levels of perturbation (with or without), and two levels of landing orientation (forward or diagonal). The center of pressure (COP), pelvic movements, and muscle activities were recorded and analyzed as the onset of COP and pelvic movement, the COP displacement, and cocontraction and reciprocal muscle activation pattern. The temporal events of COP and pelvic movement were not significantly different in all experimental conditions. However, COP and pelvic movement were significantly later in the diagonal condition. Most of the segments showed reciprocal muscle activation patterns in relation to the perturbation released time. Subsequently, all segments showed cocontraction muscle activation patterns, which was significantly affected by step side, perturbation, and orientation. The results suggest that how the CNS initiated a step was identical with the COP then pelvic movement. The outcome highlights the importance of external perturbation and foot landing orientation effects on postural adjustments, which may provide a different approach to help step initiation.


Apelin supports primary rat retinal Müller cells under chemical hypoxia and glucose deprivation.
Müller cells support the integrity of the blood-retinal barrier, whereas their dysfunction under pathological conditions may contribute to retinal edema formation. The apelin peptide, as the endogenous ligand of G protein-coupled receptor APJ, participates in numbers of physiological and pathological processes. Recent studies highlight its emerging role against ischemic injury. Our study aimed to investigate the potential neuroprotection of apelin for primary rat retinal Müller cells under hypoxia or glucose-deprivation (GD) by cell viability, migration and apoptosis, as well as apelin/APJ immunofluorescence labeling and mRNA expression. The results showed that exogenous apelin significantly stimulated Müller cells viability and migration under normal, hypoxic and glucose-free condition, also prevented apoptosis. Apelin immunoreactivities represented weak and diffuse staining in the cytoplasm, along with restricted nuclear APJ expression. They both appeared stronger immunoreactivities after 12h hypoxia. Under hypoxic stress, apelin mRNA expression began to increase at 6h (9.97 folds, p<0.01), and APJ mRNA also up-regulated (2h 6.50 folds, p<0.05; 4h 2.25 folds, p<0.05; 6h 14 folds, p<0.01), whereas they both down-regulated during 4-12h GD. Our results suggested that apelin induced the tolerance of Müller cells to hypoxia and GD. Its administration might be a promising protection for blood-retinal barrier to ischemia.


[Congenital cyst of the common hepatic duct. Adenocarcinoma of the gall bladder and of the stomach (author's transl)].
The authors report an unusual case of coexistence in the same patient of a congenital cyst of the common bile duct, a mucous adenocarcinoma of the stomach and a gall bladder adenocarcinoma. There was a favourable short term course after gastrectomy, cholecystectomy and resection of the cyst followed by bilio-digestive anastomosis on a long jejunal Y-shaped loop. The authors review recent literature.


Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice.
Cerebral ischemia induces the expression of several growth factors and cytokines, which protect neurons against ischemic insults. Recent studies showed that granulocyte colony-stimulating factor (G-CSF) has a neuroprotective effect through the signaling pathway for the antiapoptotic cascade. The current study was designed to assess the neuroprotective mechanisms of G-CSF in ischemia/reperfusion injury using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). Mice were subjected to ischemia/reperfusion and divided into two groups: those treated with G-CSF (G-CSF group) and vehicle (control group) (n = 35 in each group). Immunohistochemistry and immunoblotting for antiapoptotic protein, nitrotyrosine, and inducible nitrate oxide synthase (iNOS) were performed. G-CSF significantly reduced stroke volume (34%, P < 0.006). G-CSF upregulated Stat3, pStat3, and Bcl-2 (P < 0.05), and suppressed iNOS and nitrotyrosine expression. In EGFP chimera mice, G-CSF decreased the migration of Iba-1/EGFP-positive bone marrow-derived monocytes/macrophages and increased intrinsic microglia/macrophages at ischemic penumbra (P < 0.05), suggesting that bone marrow-derived monocytes/macrophages are not involved in G-CSF-induced reduction of ischemic injury size. Our study indicated that G-CSF exerts a neuroprotective effect through the direct activation of antiapoptotic pathway, and suggested that G-CSF is important for expansion of the therapeutic time window in patients with cerebral ischemia.


Gene-environment interactions between CD14 C-260T and endotoxin exposure on Foxp3+ and Foxp3- CD4+ lymphocyte numbers and total serum IgE levels in early childhood.
Innate immune system stimuli, such as endotoxin, seem to affect allergy risk. Previously, we described gene-environment interactions between the endotoxin receptor polymorphism C-260T of the CD14 gene and endotoxin exposure on total serum IgE level; however, the mechanism of this interaction is not known. To examine whether this gene-environment interaction affects early CD4(+)Foxp3(-) or CD4(+)Foxp3(+) lymphocyte numbers. Participating children were part of a birth cohort in the Detroit metropolitan area. Participants were genotyped for the CD14 C-260T polymorphism. Endotoxin exposure was estimated from dust measured in the home when children were 6 months old. Intracellular Foxp3 protein expression, a regulatory T-cell marker, was used to characterize CD4(+) lymphocytes in blood samples collected at the age of 12 months; total serum IgE level was also measured at this time. Because race/ethnicity may confound or modify genetic associations, all analyses were stratified by race/ethnicity. We observed a significant gene-environment interaction between CD14 C-260T genotype and endotoxin exposure on CD4(+) lymphocyte numbers, particularly CD4(+)Foxp3(-) lymphocytes. Stratified analyses suggest effect modification by race/ ethnicity on CD4(+)Foxp3(+) lymphocyte numbers, with a significant interaction in African American children but not in white children. The interaction between CD14 C-260T genotype and endotoxin exposure on total IgE levels was opposite that observed for CD4(+) lymphocyte numbers, suggesting reciprocal relationships. A gene-environment interaction between endotoxin and CD14 C-260T genotype on IgE levels may be the result of an upstream, opposing effect on CD4(+)Foxp3(+) and CD4(+)Foxp3(-) lymphocyte numbers. Race/ethnicity may affect which of these cell populations is affected by this gene-environment interaction.


Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway?
We previously made the hypothesis that STING contributes to COVID-19. The present review detail new arguments for over-activation of STING pathways in COVID-19, following the description of hyper-coagulability and Kawasaki-like diseases in children. Indeed, Kawasaki disease is induced by overreaction of innate cells following exposition to various viruses, including herpes viruses which trigger STING. It predisposes to diffuse vasculitis and aneurysms, whereas STING is over-expressed in arterial aneurisms. The redness at the inoculation site of bacillus Calmette-Guérin, a specific feature of Kawasaki disease, is reproduced by activation of the STING pathway, which is inhibited upstream by aspirin, intravenous immunoglobulins, and Vitamin-D. SARS-CoV2 binding to ACE2 can lead to excessive angiotensin II signaling, which activates the STING pathway in mice. Over-activation of the STING-pathway promotes hyper-coagulability through release of interferon-β and tissue factor by monocytes-macrophages. Aspirin and dipyridamole, besides their anti-platelet activity, also reduce tissue factor procoagulant activity, and aspirin inhibits the STING pathway upstream of STING. Aspirin and dipyridamole may be used, in combination with drugs blocking downstream the activation of the STING pathway, like inhibitors of IL-6R and JAK/STAT pathways. The risk of bleeding should be low as bleeding has not been reported in severe COVID-19 patients.


Involvement of an FtsH homologue in the assembly of functional photosystem I in the cyanobacterium Synechocystis sp. PCC 6803.
The Synechocystis sp. PCC 6803 genome encodes four putative homologues of the AAA protease FtsH, two of which (slr0228 and sll1463) have been subjected to insertional mutagenesis in this study. Disruption of sll1463 had no discernible effect but disruption of slr0228 caused a 60% reduction in the abundance of functional photosystem I, without affecting the cellular content of photosystem II or phycobilisomes. Fluorescence and immunoblotting analyses show reductions in PS I polypeptides and possible structural alterations in the residual PS I, indicating an important role for slr0228 in PS I biogenesis.


Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P synthase.
Myo-inositol exerts behavioral effects in animal models of psychiatric disorders and is effective in clinical trials in psychiatric patients. Interestingly, epi-inositol exerts behavioral effects similar to myo-inositol, even though epi-inositol is not a substrate for synthesis of phosphatidylinositol. We postulated that the behavioral effects of epi-inositol may be due to its effects on gene expression. Yeast INO1expression was measured in northern blots. INM1 was determined by beta-galactosidase activity in a strain containing the fusion gene INM1-lacZintegrated into the genome. Epi-inositol affects regulation of expression of the INO1 gene (encoding inositol-1-P synthase), even though it cannot support growth of an inositol auxotroph (suggesting that, as in mammalian cells, it is not incorporated into phosphatidylinositol). Like myo-inositol, although to a lesser extent, epi-inositol causes a significant reduction in INO1 expression, and reverses the lithium- or valproate-induced increase in INO1 expression. However, it does not affect regulation of INM1 (encoding inositol monophosphatase), the expression of which is up-regulated by myo-inositol. The observed regulatory effects of epi-inositol on expression of the most highly regulated gene in the inositol biosynthetic pathway may help to explain how this inositol isomer can exert behavioral effects without being incorporated into phosphatidylinositol.


[Stable postoperative phase after total artificial heart-replacement in animal-experiments (author's transl)].
Presented are results of an analysis of more than 30000 data which were sampled in seven long-surviving calves after total artificial heart-replacement (more than 35 days survival). The continuity of 24 types of data (hemodynamic, labor- and physical data) are transformed for every animal in time-equidistant datafields and after this an average continuity for all seven animals is calculated and plotted. Twenty days after the operation the data have reached the preoperative values in nearly all cases, indicating a stable phase starting, according to the clinical condition of the animals.


The common consensus criteria have high predictive values for long-term postoperative acromegaly remission.
The aim of this work was to retrospectively study the long-term reliability of the common consensus endocrinological criteria for the assessment of postoperative remission of acromegaly. In 96 consecutive patients, surgical remission of acromegaly following transsphenoidal surgery was considered to be present when, without adjuvant treatment, 3 months postoperatively there was no clinical evidence of persisting disease, and, according to the common consensus criteria for acromegaly remission, GH was suppressed to < 1 μg/l during the oral glucose tolerance test (OGTT) and insulin like growth factor-1 (IGF-1) was within normal limits. The results of the second postoperative week, 3 months postoperative, and the most recent follow-up OGTT and IGF-1 measurements were used to calculate the positive and negative predictive values of the following endocrinological criteria of acromegaly remission: the common consensus criteria for acromegaly remission, GH suppression to < 1 μg/l during OGTT and IGF-1 within normal limits. Sensitive IRMA (≤ 0.3 μg/l) and RIA (≤ 32 μg/l) assays for GH and IGF-1 were used. The surgical remission rate of acromegaly was 72.9%. At a median follow-up of 5.06 years, the recurrence rate of acromegaly was 2.08%. Overall, the common consensus criteria for acromegaly remission were the most reliable tests, with the following positive and negative predictive values at 2 weeks postoperatively, 3 months postoperatively and at the most recent follow-up: 68%, 100% and 100%, and 98%, 100% and 100%, respectively. The negative likelihood ratio confirmed that the test qualities of the common consensus criteria for acromegaly remission were superior to the other tests. The common consensus criteria were the most reliable tests for the diagnosis of postoperative acromegaly remission. The positive and negative predictive values of the common consensus criteria for acromegaly remission increased from the second postoperative week to 3 months postoperatively, thereafter reliably indicating the long-term results of transsphenoidal surgery.


Estimation of hydrodynamic shear stresses developed on human osteoblasts cultured on Ti-6Al-4V and strained by four point bending. Effects of mechanical loading to specific gene expression.
The aim of the present investigation was to study the effects of mechanical strain on the orthopedic biomaterial Ti-6Al-4V-osteoblast interface, using an in vitro model. Homogeneous strain was applied to Human Bone Marrow derived Osteoblasts (HBMDOs) cultured on Ti-6Al-4V, at levels which are considered physiological, by a four-point bending mechanostimulatory system. A simple model for the estimation of maximum hydrodynamic shear stresses developed on cell culture layer and induced by nutrient medium flow during mechanical loading, as a function of the geometry of the culture plate and the load characteristics, is proposed. Shear stresses were lower than those which can elicit cell response. Mechanical loading was found that contributes to the regulation of osteoblast differentiation by influencing the expression of the osteoblast-specific transcription factor Cbfa1, both at the mRNA and protein level, and also the osteocalcin expression, whereas osteopontin gene expression was unaffected by mechanical loading at all experimental conditions.


Injection of prototypic celiac anti-transglutaminase 2 antibodies in mice does not cause enteropathy.
Celiac disease is an autoimmune enteropathy driven by dietary intake of gluten proteins. Typical histopathologic features are villous flattening, crypt hyperplasia and infiltration of inflammatory cells in the intestinal epithelium and lamina propria. The disease is hallmarked by the gluten-dependent production of autoantibodies targeting the enzyme transglutaminase 2 (TG2). While these antibodies are specific and sensitive diagnostic markers of the disease, a role in the development of the enteropathy has never been established. We addressed this question by injecting murine antibodies harboring the variable domains of a prototypic celiac anti-TG2 immunoglobulin into TG2-sufficient and TG2-deficient mice evaluating for celiac enteropathy. We found no histopathologic abnormalities nor clinical signs of disease related to the injection of anti-TG2 IgG or IgA. Our findings do not support a direct role for secreted anti-TG2 antibodies in the development of the celiac enteropathy.


Growth-stimulatory action of plasma membrane-associated growth factor. A synergistic effect with platelet-poor plasma.
Growth factor activity was partially purified from mouse liver plasma membranes and its growth-stimulatory action on cultured mouse fibroblasts was studied. The plasma membrane-associated growth factor (PMGF) was unable to support the proliferation of mouse fibroblasts in monolayer when added as the sole source of growth factor. However, it stimulated the growth of fibroblasts in the presence of CM-Sephadex-treated human platelet-poor plasma (h-CMP) which by itself is not growth-stimulatory. The stimulation of DNA synthesis in quiescent fibroblasts was also observed upon the addition of PMGF and h-CMP. Under the same conditions, both platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) showed the same effect as did PMGF. The synergistic action of h-CMP with PMGF on quiescent cells was partially reproduced by insulin at microgram quantities or by insulin-like growth factor I(IGF-I) at nanogram quantities. Thus, the data presented here indicates that the action of PMGF is similar to that of the family of growth factors termed 'competence factor', and distinct from that of plasma growth factors termed 'progression factor'.


Pesticide-induced decrease in rat testicular steroidogenesis is differentially prevented by lipoate and tocopherol.
We have previously demonstrated that the sub-chronic administration of low doses of Toc or α-Toc, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5 weeks) provoked severe oxidative stress (OS) in testicles. These effects were also reflected in plasma. Lipoic acid (LA) and α-tocopherol are considered as antioxidants due to their ability to neutralize reactive oxygenated species (ROS) and reset endogenous antioxidant levels. To investigate the possible protective effect on reproductive function, LA and Toc (i.p. 25, 50 and 100mg/kg) were administered simultaneously with the pesticide mixture (PM) for 5 weeks. Both drugs prevented OS and the damage to proteins and lipids caused by PM in a dose-dependent manner. The PM-induced increase levels of prostaglandins E2 and F2α was completely restored by LA but not by Toc. Similarly, only LA was able to restore the inhibition of testosterone production, the decrease of 3β- and 17β-hydroxysteroid dehydrogenases activities, and the elevation of gonatropins (FSH and LH) levels produced by PM. Furthermore, LA was more efficient than Toc in normalizing the histological alterations produced by PM administration, suggesting that pesticides act though other mechanisms that generate oxidative stress. In our experimental model LA displayed a higher protective role against pesticide-induced damage than that observed by Toc administration. Our results suggest that LA administration is a promising therapeutic strategy for coping with disorders suspected to be caused by OS generators - such as pesticides - in male reproductive system.


Pathology of the adult respiratory distress syndrome.
Despite the wide range of insults that can lead to the development of ARDS, a common sequence of pathologic changes can be identified in the lung. These changes can be divided into three phases: the acute, or exudative, phase (up to 6 days), in which hyaline membranes are a characteristic feature; the subacute, or proliferative, phase (4 to 10 days), in which metaplasia of the alveolar lining cells and early evidence of fibrosis are seen; and the chronic phase (8 days and on), when organizing fibrosis is a major finding. Structural changes of chronic pulmonary hypertension are also found in the patients with ARDS of longer duration. The mechanism by which these pulmonary changes occur is unknown. Studies of experimental models of ARDS may offer the best opportunity to elucidate the mechanisms. For example, a single infusion of E. coli endotoxin into sheep mimics the pathophysiologic changes of ARDS, offering a model for study of the initial insult on the lung. In addition, animals exposed to high concentrations of oxygen also show morphologic changes similar to those seen in patients with ARDS. Whether the hyperoxia is responsible for such changes, or whether it potentiates the injury induced by some other insult, is not certain.


Antibacterial activity and phytochemical components of leaf extract of Calpurnia aurea.
Local Ethiopians use Calpurnia aurea to treat skin infections. However, there is no adequate scientific confirmation. The aim of this study was to evaluate the antibacterial activities of the crude and the fractionated extracts of C. aurea leaves against different bacterial strains. The crude extract was made by maceration. The Soxhlet extraction method was used to obtain fractional extracts. The antibacterial activity against gram positive and gram negative American Type Culture Collection (ATCC) strains was performed using the agar diffusion technique. The minimum inhibitory concentration was determined through the microtiter broth dilution method. Preliminary phytochemical screening was done using standard techniques. The largest yield was obtained from ethanol fractional extract. Except for chloroform, which provided a relatively low yield when compared to petroleum ether, increasing the polarity of the extracting solvent improved the yield. The crude extract, solvent fractions, and the positive control showed inhibitory zone diameter, while the negative control did not. When used at a concentration of 75 mg/ml, the crude extract had similar antibacterial effects as gentamicin (0.1 mg/ml) and the ethanol fraction. The 2.5 mg/ml crude ethanol extract of C. aurea suppressed the growth of Pseudomonas aeruginosa, Streptococcus pneumoniae, and Staphylococcus aureus, according to the MIC values. The extract of C. aurea was more effective in inhibiting P. aeruginosa than the other gram-negative bacteria. Fractionation enhanced the antibacterial effect of the extract. All fractionated extracts showed the highest inhibition zone diameter against S. aureus. Petroleum ether extract had the greatest inhibition zone diameter against all bacterial strains. The non-polar components were more active compared to the more polar fractions. The phytochemical components discovered in the leaves of C. aurea included alkaloids, flavonoids, saponins, and tannins. Among these, the tannin content was remarkably high. The current results could provide a rational support for the traditional use of C. aurea to treat skin infections.


Functional neuroanatomical networks associated with expertise in motor imagery.
Although numerous behavioural studies provide evidence that there exist wide differences within individual motor imagery (MI) abilities, little is known with regards to the functional neuroanatomical networks that dissociate someone with good versus poor MI capacities. For the first time, we thus compared, through functional magnetic resonance imaging (fMRI), the pattern of cerebral activations in 13 skilled and 15 unskilled imagers during both physical execution and MI of a sequence of finger movements. Differences in MI abilities were assessed using well-established questionnaire and chronometric measures, as well as a new index based upon the subject's peripheral responses from the autonomic nervous system. As expected, both good and poor imagers activated the inferior and superior parietal lobules, as well as motor-related regions including the lateral and medial premotor cortex, the cerebellum and putamen. Inter-group comparisons revealed that good imagers activated more the parietal and ventrolateral premotor regions, which are known to play a critical role in the generation of mental images. By contrast, poor imagers recruited the cerebellum, orbito-frontal and posterior cingulate cortices. Consistent with findings from the motor sequence learning literature and Doyon and Ungerleider's model of motor learning [Doyon, J., Ungerleider, L.G., 2002. Functional anatomy of motor skill learning. In: Squire, L.R., Schacter, D.L. (Eds.), Neuropsychology of memory, Guilford Press, pp. 225-238], our results demonstrate that compared to skilled imagers, poor imagers not only need to recruit the cortico-striatal system, but to compensate with the cortico-cerebellar system during MI of sequential movements.


Microglial ontogeny, diversity and neurodevelopmental functions.
Microglia are instrumental to the development, function, homeostasis and pathologies of the central nervous system. These brain-resident macrophages arise early in embryogenesis and seed the developing brain, where they differentiate in response to cues provided by their neural niche. Throughout life, microglia regulate the neural tissue through a variety of cellular functions influenced by intrinsic and extrinsic factors. Despite their importance, we are only starting to uncover how microglia colonize the brain, adopt distinct functional states during development and the long-term impact of early alteration of their functions. This review highlights the latest knowledge on the ontogeny of microglia, their developmental trajectory and emerging roles. Characterizing these processes will be critical for our understanding of both brain physiology and pathologies.


Influence of individual differences in Behavioral Inhibition System on the magnitude and time course of the fear-potentiated startle.
Previous research has shown that the startle reflex is potentiated during experimentally induced anxiety (fear-potentiated startle). In the present study, the magnitude and time course of the startle blink reflex were examined among 35 undergraduates scoring one standard deviation above (n = 14) or below (n = 21) the mean in a self-report measure of sensitivity to punishment (SP) in a paradigm involving the anticipation of electric shocks. Contrary to our predictions, SP did not relate to differences in the magnitude or in the time course of fear-potentiated startle. Our data do not support an association between this individual differences variable and the fear-potentiated startle.


Comparative Analysis of Costs of Caring for Inpatient COVID-19 Patients and Non-COVID-19 Patients at One Academic Center.
The coronavirus disease 2019 (COVID-19) pandemic has created a significant financial burden on the US healthcare system. The purpose of this study was to compare the costs of caring for patients admitted with COVID-related illness versus non-COVID patients. We hypothesized that the average daily costs of hospitalization would be higher among COVID patients compared with non-COVID patients. This was a retrospective cohort study. Data were downloaded for patients who were admitted at Atrium Wake Forest Baptist Hospital from January 1, 2020 through February 28, 2021. The study population was dichotomized by COVID and non-COVID patients, and the average daily hospital cost was calculated. Multivariate adjusted linear regression models were used to calculate additional "average daily cost" comparisons. The COVID group was slightly older (mean age 61.0 vs 58.0 years), with longer mean length of stay (6.12 vs 4.95 days) and higher mean average daily direct cost ($1504.01 vs $1341.30) when compared with the non-COVID group, respectively (P < 0.001). After adjusting for various patient characteristics, the direct inpatient cost was $123.00 (95% confidence interval 74.4-171.5) higher per day in patients with COVID-19 (P < 0.0001). When indirect costs are considered, the combined indirect and direct cost may be four times greater. The average daily direct hospital cost is higher among patients with COVID compared with non-COVID-related illness. Many reasons contributed to this cost difference, including decreased nurse staffing ratios, lower physician censuses, and needed infrastructure changes. Studies with a larger sample size and more precise comparable study groups are warranted to validate our findings.


Infusion of human insulin-like growth factor I (IGF-I) into malnourished rats reduces hepatic IGF-I mRNA abundance.
To determine whether the serum level of IGF-I influences its hepatic synthesis through negative feedback regulation, we infused 200 micrograms/d of human IGF-I subcutaneously into young male rats eating either an energy-restricted or ad lib diet. In energy-restricted rats, a two-fold increase in serum IGF-I concentration produced a 41% increase in growth rate at the end of one week, and a 30% decrease in steady state hepatic IGF-I mRNA and 56% drop in serum GH at the end of two weeks. In ad lib fed rats, the increased serum IGF-I concentration neither enhanced growth rate nor significantly reduced hepatic IGF-I mRNA abundance or serum GH levels. These data suggest that the abundance of hepatic IGF-I mRNA in energy-restricted rats is controlled, in part, by serum IGF-I levels via negative feedback regulation.


How far can hydroxyl radicals travel? An electrochemical study based on a DNA mediated electron transfer process.
Using photocatalytic reactive nanoparticles and DNA composite modified gold electrodes, exploiting the sensitivity of DNA-mediated electron transfer to base pair stacking, we examined the effects of DNA oxidation damage by photocatalytically generated hydroxyl radicals (˙OH) on charge transfer efficiency and proposed an electrochemical technique to read the effective diffusing distance of ˙OH.


Pulmonary calcifications in a child with renal failure.
A chronically azotemic 2 6/12 boy developed diffuse, bilateral pulmonary calcification. The radiographic features and pathologic mechanism of such pulmonary calcification is discussed.


Protecting the oral mucosa in patients with oral tongue squamous cell carcinoma treated postoperatively with intensity-modulated radiotherapy: a randomized study.
Is the severity of acute oral mucositis in patients who receive postoperative intensity-modulated radiotherapy (PO-IMRT) for oral tongue squamous cell carcinoma (SCC) reduced by sparing the oral mucosa outside of the planning target volume (PTV)? Prospective, randomized trial. Forty-eight patients with oral tongue SCC who received PO-IMRT at our institution were randomized to two groups: the oral-sparing (OR-SP) group and oral-unsparing (OR-USP) group. For the OR-SP group (n = 24), the oral mucosa outside of the PTV was spared. Furthermore, the mucosa including the bilateral cheeks, upper lip, and lower lip was defined as the united site and given <32 Gy. For the OR-USP group (n = 24), none of the oral mucosa was protected. The severity of clinical acute mucositis in each patient was assessed weekly during PO-IMRT until completely healed. Oral mucositis was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Dosimetry and therapeutic measures related to acute mucositis between the two groups were compared. During PO-IMRT, no patient experienced grade 4+ acute mucositis in any oral site. Compared to the OR-USP group, there was less grade 2 and 3 mucositis in the united site of the OR-SP group (0% and 25% vs. 45.8% and 54.2%, respectively; P = .000). Also, the mean dose to the united site was significantly lower with OR-SP compared to OR-USP (41.8 ± 7.4 Gy vs. 58.8 ± 2.2 Gy; P = .000). The OR-SP group was associated with significant reductions in the use of analgesics (P = .043) and intravenous antibiotics (P = .039). No recurrences were detected in the vicinity of the spared oral mucosa (the united site) during a median follow-up time of 30 months. OR-SP PO-IMRT for patients with oral tongue SCC resulted in a significant decrease in the severity of acute mucositis and improved quality of life. The sparing of the oral mucosa outside of the PTV is safe and does not compromise oncologic outcomes.


Reconstruction of lower eyelid and periorbital district: an orbicularis oculi myocutaneous flap.
The upper eyelid has long been considered a good source of skin graft, but it is infrequently used as a unipedicled flap, based either medially or laterally, to reconstruct the skin of the lower eyelid. Here we describe a procedure in which we use the upper eyelid skin and underlying orbicularis muscle as a myocutaneous flap to reconstruct the lower eyelid and periorbital region.


Staining of the Ca2+-binding proteins, calsequestrin, calmodulin, troponin C, and S-100, with the cationic carbocyanine dye "Stains-all".
The Ca2+-binding proteins, calsequestrin, calmodulin, troponin C, and S-100, have all been shown to stain dark blue or purple with the cationic carbocyanine dye "Stains-all", while most proteins stain red or pink. Stains-all staining of these Ca2+-binding proteins was 50-100% more intense than Coomassie blue staining, and the blue stained calsequestrin and troponin C could be detected in muscle extracts. Densitometric scans of Stains-all-stained gels revealed that interaction of the dye with Ca2+-binding proteins changed the absorption spectrum of the dye. The dye-protein complex absorbed maximally at 615 nm, reflecting a state that results from the binding of individual dye molecules at anionic sites. Stains-all also interacted with undenatured Ca2+-binding proteins in aqueous solution forming a complex absorbing maximally at 600 nm. A simple assay for Ca2+-binding proteins has been developed using this property. These results suggest that the interaction of the dye with anionic sites within these Ca2+-binding proteins produces the dye-protein complex which absorbs at 600-615 nm. Stains-all staining of these Ca2+-binding proteins will be useful in their identification and purification from various tissues. It might also be a valuable tool in the identification of potential Ca2+-binding proteins.


Penetration analysis of elements and bioleaching treatment of spent refractory for recycling.
Acidithiobacillus ferrooxidans ATCC23270 and Acidithiobacillus thiooxidans TM-32 were used for bioleaching of spent refractories of aluminium and copper melting furnaces for their recycling. Firstly, penetration of elements into aluminium melting furnace refractory was investigated and it was found that up to 7 cm from surface was contaminated. Comparison on leaching efficiency by the strains ATCC23270 and TM-32 found that the strain ATCC23270 could treat larger amount of the refractories than the strain TM-32 could do. In the experiment of bioleaching of spent refractory aluminium melting furnace by the strain ATCC23270, high leaching efficiency were obtained on Al, Si, and Ca, and extremely low leaching performance was, however, shown on the rest of elements i.e., Na, Mn, and Zn. Under the strain TM-32 use, relatively high leaching performance was recognized on Al, Si, Ca, Na, Mn, and Zn. In the experiment of bioleaching for spent refractory copper melting furnace, almost the same leaching trends were shown on Cu, Zn, Al, and Si under the strains ACTT23270 and TM-32 uses.


Teacher practices as predictors of children's classroom social preference.
Students who do not get along with their peers are at elevated risk for academic disengagement and school failure. Research has predominantly focused on factors within such children that contribute to their peer problems. This study considers whether teacher practices also predict social preference for children in that classroom. Participants were 26 elementary school teachers and 490 students in their classrooms followed for one school year. Results suggested that teachers who favored the most academically talented students in the fall had classrooms where children had lower average social preference in the spring after statistical control of children's fall social preference and externalizing behavior problems. Teachers who demonstrated emotionally supportive relationships with students in the fall had classrooms where children had greater possibility of changing their social preference from fall to spring. Although children with high externalizing behaviors tended to experience declining social preference over the course of the school year, teachers' learner-centered practices attenuated this progression. However, teachers' favoring of the most academically talented accentuated the negative relation between externalizing behaviors and social preference. Implications for school psychology practitioners are discussed.


Dissociation of active from immobility components of sexual behavior in female rats by central 6-hydroxydopamine: implications for CA involvement in sexual behavior and sensorimotor responsiveness.
Ovariectomized female rats were given a hormone treatment (2 X 8 micrograms/kg estradiol benzoate) that normally supports only low levels of lordosis responding and no soliciting behavior in tests with sexually active males. When subjected to an intraventricular 6-hydroxydopamine (6-OHDA) procedure (with pargyline pretreatment) that produced 85% and 95% depletions of caudate dopamine and cortical norepinephrine respectively, these females exhibited a dramatic increase in the intensity and frequency of lordotic responding but no soliciting behavior over 3 weekly tests. The increase in lordosis was not due to a drug- or stress-induced release of adrenal progesterone, since dexamethasone suppressed the progesterone levels, as documented by radioimmunoassay, but not the higher receptivity of 6-OHDA treated females. In other ovariectomized females given a hormone regimen (2 X 50 micrograms/kg estradiol benzoate plus 500 micrograms progesterone) that supported maximal levels of lordosis and soliciting, the same 6-OHDA treatment prolonged the average duration of lordosis while actually decreasing the incidence and duration of soliciting. The hypothesis is put forward that the differential effects of interfering with catecholamine, and more likely dopamine function on the soliciting and lordosis components of female sexual behavior might best be understood as a dissociation between mutually antagonistic behavior patterns such that responsiveness involving active orientation and forward locomotion is suppressed, whereas responses requiring immobility are augmented.


Effectiveness and methods of cryotherapy in reducing swelling after total knee arthroplasty: A systematic review on randomized controlled trials.
This study aims to investigate the effect and methods of cryotherapy in reducing swelling after total knee arthroplasty. Systematic review. We searched PubMed, Embase, CINAHL, Cochrane Library, KoreaMed, KERIS and National Science Digital Library for randomized controlled trials on 19 August 2021. This systematic review was conducted according to the PRISMA 2009 checklist. A total of eight randomized controlled trials were systematically reviewed to determine the effect and methods of cryotherapy on reducing postoperative swelling. The effects were not significantly different in six studies. Application time per cryotherapy session was 10-20 min when using an ice pack and up to 48 h when using an automated device. The duration ranged from 2 days to 1 week or until discharge, and the frequency varied from 2 to 72 times per day.


Gemcitabine plus celecoxib (GECO) in advanced pancreatic cancer: a phase II trial.
Single agent gemcitabine (GEM) is the standard treatment of pancreatic adenocarcinoma. Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. Recent studies in human pancreatic tumor cell lines suggest an involvement of COX-2 in tumor-dependent angiogenesis and provide the rational for inhibition of the COX pathway as an effective therapeutic approach. The aim of this study is to evaluate the toxicity and activity of gemcitabine plus celecoxib. Forty-two consecutive patients with histologically or cytologically confirmed pancreatic adenocarcinoma entered the trial. Twenty-six patients (pts) were metastatic, 16 pts had locally advanced disease. The schedule consisted of GEM 1,000 mg/m2 (as a 30 min iv infusion) on days 1, 8 every 3 weeks and celecoxib 400 mg bid. Four pts (9%) achieved a partial response and 26 (62%) had stable disease, gaining a total disease control in 30 pts (71% [95% CI, 58-84%]). Overall clinical benefit response was experienced by 23 pts (54.7% [95%CI, 38.6-70.1%]). Neither grade 4 neutropenia nor grade 3-4 thrombocytopenia was observed. Grade 3 neutropenia was detected in 19% of pts. Grade 3 non-hematological toxicity was as follows: hepatic toxicity 7%, nausea 2.3%. Three pts (7%) and 5 pts (12%) had respectively a minimum creatinine increase and edema. Median survival was 9.1 months (95% CI, 7.5-10.6 months). GEM in combination with celecoxib showed low toxicity, good clinical benefit rate and good disease control. Further clinical investigation is warranted.


[Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area].
To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area. The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes. Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in <1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05). The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.


The effect of psychotherapeutic interventions on positive and negative affect in depression: A systematic review and meta-analysis.
Depression is a mental disorder characterized by high and dysregulated negative affect in addition to diminished positive affect. To our knowledge, there has been no systematic review of the impact of psychotherapeutic interventions on these affective dimensions. Two comprehensive literature searches for all randomized controlled trials of psychotherapy in adults with depression were performed. The first from 1996 to December 31, 2014 and the second from January 1, 2015 to December 31, 2015. The primary outcome was the mean score of positive and negative affect. Depressive symptoms were measured to be included as a predictor in the meta-regression analyses. Ten studies with 793 adults with depression were included. All studies assessed positive and negative affect. Psychotherapeutic interventions resulted in significantly increased positive affect (g=0.41; 95% CI: 0.16-0.66 p=0.001), and significantly decreased negative affect (g=0.32; 95% CI: 0.15-0.78, p=0.001) in depressed adults. Because of the small number and substantial heterogeneity of the existing studies the meta-regression analyses produced conflicting results. As a consequence, we were unable to sufficiently demonstrate whether NA and depressive symptoms are in fact correlated or not. Given the small number and heterogeneity of the included studies, the findings should be considered with caution. Psychotherapeutic interventions demonstrate low to moderate effects in enhancing positive and reducing negative affect in depressed adults.


Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: A large, multicenter retrospective analysis.
Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.


Comparison of four basic models of indirect pharmacodynamic responses.
Four basic models for characterizing indirect pharmacodynamic responses after drug administration have been developed and compared. The models are based on drug effects (inhibition or stimulation) on the factors controlling either the input or the dissipation of drug response. Pharmacokinetic parameters of methylprednisolone were used to generate plasma concentration and response-time profiles using computer simulations. It was found that the responses produced showed a slow onset and a slow return to baseline. The time of maximal response was dependent on the model and dose. In each case, hysteresis plots showed that drug concentrations preceded the response. When the responses were fitted with pharmacodynamic models based on distribution to a hypothetical effect compartment, the resulting parameters were dose-dependent and inferred biological implausibility. Indirect response models must be treated as distinct from conventional pharmacodynamic models which assume direct action of drugs. The assumptions, equations, and data patterns for the four basic indirect response models provide a starting point for evaluation of pharmacologic effects where the site of action precedes or follows the measured response variable.


Behavioural studies of spatial vision in cats reared with convergent squint: is amblyopia due to arrest of development?
Visual acuity and contrast sensitivity were measured behaviourally in normal adult cats and cats reared with monocular convergent squint from 3, 6, 8, 12, and 24 weeks of age. The visual acuity of the squinting eye was significantly lower than that of the non-squinting eye in cats with squint from 3, 6, and 8 weeks of age. No significant difference in acuity between eyes was found in the 12- and 24-week squinting cats and in the controls. Contrast thresholds at all spatial frequencies tested (range 0.13--2.0 c/degrees) were higher in the squinting eye than in the non-squinting eye of cats with squint from 3 and 6 weeks of age, but differences were greater at the higher spatial frequencies. In the 8-week squinting cat, contrast thresholds were increased only at higher spatial frequencies. No significant differences in contrast sensitivity were found in the cat with squint from 24 weeks of age and in the controls. The degree of disturbance of spatial vision in squinting cats was most related to the age at onset of the squint, i.e., the earlier the onset, the more profound the amblyopia. The period of susceptibility extended from about 3 to 12 weeks of age. When compared with data on the development of visual acuity in kittens, the pattern of results from the present study suggests that convergent squint can arrest the development of spatial vision.


New method of simulation to evaluate the sensitivity to oxidation of lubricating oils: an aging cell coupled with fourier transform infrared spectroscopy.
This study presents a new method for evaluating the oxidation of lubricating oils. An aging cell adapted to a Fourier transform infrared (FT-IR) spectrometer allows the continuous and direct study of the oxidative aging of base oils. During the test, oxidation bands appeared in the spectra (carbonyl bands around 1730 cm(-1)). The graphic representation of the carbonyl band modification--using a spectroscopic index--makes it possible to monitor the evolution of the lubricant composition. Comparing the oxidation constants, determined from the kinetic plots of several base oils, makes it possible to evaluate their relative sensitivity.


Platelet alpha granule depletion: findings in patients with prosthetic heart valves and following cardiopulmonary bypass surgery.
The alpha granule content of platelets, as indicated by the amount of beta-thromboglobulin (beta-TG) in lysed platelet rich plasma was measured to determine whether platelet stimulation resulted in a circulating population of granule-depleted platelets. In 101 normal controls, with a mean platelet count of 242.6 +/- 6.5 X 10(9)/1, the mean platelet beta-TG content was 55.9 +/- 1.2 ng/10(6) platelets. There was a significant reduction in both these parameters (mean platelet count 195.5 +/- 5.8 X 10(9)/1 (P less than 0.001), mean platelet beta-TG 50.0 +/- 1.2 ng/10(6) platelets (P less than 0.01)) in 74 patients with prosthetic cardiac valves. In 24 patients, cardiopulmonary bypass surgery caused a much greater reduction in median platelet count from 210 X 10(9)/1 to 11.1 X 10(9)/1, two hours after surgery (P less than 0.001) but no overall change in platelet beta-TG. However, five patients who experienced diffuse haemorrhage in the postoperative period had a lower median platelet beta-TG (35.5 ng/10(6) platelets) than the other 19 patients (51.0 ng/10(6) platelets) (P less than 0.05).


Prenatal closure of abdominal defect in gastroschisis: case report and review of the literature.
With the routine use of fetal imaging studies during prenatal care, increased numbers of unusual intrauterine events are now detected. Prenatal closure of the abdominal defect in gastroschisis is an example. We report a 34 5/7-week stillborn who had prenatal closure of a ventral abdominal wall defect, which had been seen earlier on fetal ultrasound examination. Two ultrasound examinations performed at 15 1/7 weeks and 19 1/7 weeks showed a mass of exteriorized bowel that herniated through the abdominal defect, just to the right of the umbilical cord. At 30 1/7 weeks, no exteriorized bowel was seen, but thickened and dilated intraabdominal bowel was identified. No abdominal defect or exteriorized bowel was found at autopsy. There was a severely dilated proximal jejunum with the absence of the rest of the small intestine and the right side of the colon. The remaining left side of the colon was small and blind proximally. Six similar isolated examples have been reported since 1991. Prenatal closure of an abdominal defect was associated with long-segment atresia of the midintestine in each case. We believe that the spontaneous closure of this abdominal defect was associated with atresia and resorption of exteriorized bowel. It is likely some of the cases of long-segment atresia may in fact be associated with closed gastroschisis.


Lipotoxicity as a trigger factor of renal disease.
In the last few decades, rapid changes in lifestyle have led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance, dyslipidemia, type 2 diabetes and kidney disease. The surplus of calories is normally stored as triglycerides in adipose tissue. However, excess lipids can also accumulate ectopically in other organs, including the kidney, contributing to their damage through toxic processes named lipotoxicity. The kidney is negatively affected by dyslipidemia, lipid accumulation and changes in circulating adipokines that bring about alterations in renal lipid metabolism and promote insulin resistance, generation of reactive oxygen species and endoplasmic reticulum stress, ultimately leading to alterations in the glomerular filtration barrier and renal failure. This review focuses on the pathogenic molecular mechanisms associated with renal lipotoxicity, and presents new insights about potential new therapeutic targets and biomarkers such as microRNAs and long non-coding RNAs, of relevance for the early detection of lipid-associated kidney disease.


The Albumin to Globulin Ratio Performs Well for Diagnosing Periprosthetic Joint Infection: A Single-Center Retrospective Study.
Accurate diagnosis of the periprosthetic joint infection (PJI) remains a challenge for surgeons. The purpose of this study was to assess the value of albumin to globulin ratio (AGR) and globulin (GLB) for diagnosing PJI. A total of 182 patients undergoing revision after arthroplasty were included and divided into 2 groups, 61 in knee group (PJI: 38; non-PJI: 23) and 121 in hip group (PJI: 26; non-PJI: 95). We used receiver operating characteristic curves to determine the diagnostic value of AGR, GLB, inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]). The receiver operating characteristic curves showed the areas under the curve of AGR, GLB, ESR, and CRP in the knee group were 0.940, 0.928, 0.867, and 0.848, respectively, and they were 0.855, 0.831, 0.886, and 0.912 in the hip group. The optimal predictive cut-off values for AGR in knee and hip groups were 1.375 and 1.295, respectively. The sensitivity and specificity of AGR, respectively, were 94.7% and 87.0% (knee group) and 84.6% and 75.8% (hip group) for diagnosing PJI. The sensitivity of "AGR or ESR" and specificity of "AGR and GLB" in the knee group were 99.6% and 98.9%, respectively. For knee or hip groups, the AGR exhibits good value for the diagnosis of PJI comparable with ESR and CRP. The AGR and GLB, together with CRP and ESR, should be used as the preferred indicators for diagnosing PJI. The "AGR or ESR" and "AGR and GLB" in the knee group have an excellent diagnostic value in sensitivity and specificity, respectively.


Comparison of manual and electric breast pumps among WIC women returning to work or school in Hawaii.
The Women, Infants, and Children (WIC) branch of the Hawaii Department of Health encourages and assists mothers in breastfeeding. A study was done to determine whether an electric breast pump (vs. a manual pump) would increase breastfeeding duration in those returning to work or school full-time. During 2002-2003, a randomized trial was conducted among 280 women, with the duration of breastfeeding analyzed in 229 of these women. Descriptive analyses and a multivariate logistic regression analysis assessed factors associated with breastfeeding at 6 months. Unadjusted and adjusted survival analyses were performed to estimate the duration of breastfeeding. In all, 76.8% of women using the manual breast pump and 72.3% of those using the electric breast pump breastfed for at least 6 months. This difference did not reach statistical significance. In the survival analysis adjusted for pump assignment, maternal age, race/ethnicity, marital status, and parity, women with at least some college education breastfed for a 38% shorter time than women with a high school or lower education. Our findings suggest that the manual breast pump may work as well as the electric breast pump when breastfeeding is encouraged and supported among women returning to work or school full-time. Particular attention should be given to examining reasons why women with greater education breastfed for a shorter duration. Further research is needed to validate these results to better inform breastfeeding women returning to work or school.


Synthesis and anticholinesterase activity of huperzine A analogues containing phenol and catechol replacements for the pyridone ring.
Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.


Effects of striatal transplantation of cells transfected with GDNF gene without pre- and pro-regions in mouse model of Parkinson's disease.
Previously, we have shown that transgenic cells bearing the GDNF gene with deleted pre- and pro-regions (mGDNF) can release transgenic GDNF. The medium conditioned by transgenic cells with mGDNF induced axonal growth in rat embryonic spinal ganglion in vitro. Here we demonstrate a neurotrophic effect of mGDNF on PC12 cells in vitro as well as its neuroprotective effect on dopaminergic neurons in the substantia nigra pars compacta in vivo as indicated by improved motor coordination and sleep-wakefulness cycle in the MPTP mouse model of Parkinson's disease. HEK293 cells were transfected with a vector encoding an isoform of the human GDNF gene with deleted pre- and pro-regions (mGDNF). This factor in the medium conditioned by the transfected cells was shown to induce axonal growth in PC12 cells. The early Parkinson's disease model was established by injection of the dopaminergic pro-neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into C57Bl/6 mice. Transgenic HEK293/mGDNF/GFP cells were transplanted into the striatum (caudate-putamen) of experimental mice. The sleep-wakefulness cycle was studied by continuous EEG and motor activity monitoring 1 and 2 weeks after MPTP injection. After the experiment, the motor coordination of experimental animals was evaluated in the rotarod test, and dopaminergic neurons in the substantia nigra pars compacta were counted in cross-sections of the midbrain. MPTP administration lowered the number of tyrosine hydroxylase immunopositive cells in the substantia nigra pars compacta, decreased motor coordination, and increased the total wake time during the dark period. The transplantation of HEK293/mGDNF cells into the caudate-putamen 3 days prior to MPTP injection smoothed these effects, while the control transplantation of HEK293 cells showed no notable impact. Transplantation of transgenic cells with the GDNF gene lacking the pre- and pro-sequences can protect dopaminergic neurons in the mouse midbrain from the subsequent administration of the pro-neurotoxin MPTP, which is confirmed by polysomnographic, behavioral and histochemical data. Hence it is released from transfected cells and preserves the differentiation activity and neuroprotective properties.


Differences in C/EBPs in normal tissue and papillomas of the larynx.
Transcription factors belonging to the family of CAAT enhancer binding proteins (C/EBPs) programme differentiation in a wide variety of cells. We asked about the expression of C/EBPs in squamous epithelium. Using immunohistochemistry, C/EBPalpha and C/EBPbeta were easily detected in tissue sections from normal larynx or laryngeal papillomas, benign tumours with a papillomavirus aetiology and characterized by abnormal differentiation. A temporal expression of these C/EBPs occured as keratinocytes differentiated. In both tissues, C/EBPbeta appeared to be exclusively nuclear. In normal tissue, the greatest amount of C/EBPbeta was present in the spinous layer, and much less occurred in the granular layer. The basal layer of the laryngeal papillomas contained the most C/EBPbeta. Less was present in the spinous layer. Little C/EBPbeta was in the granular layer. Much C/EBPalpha was in the cytoplasm in both tissues. In normal tissue, nuclear C/EBPalpha staining was virtually absent in the basal layer, and became present in the spinous layer. Nuclear C/EBPalpha was randomly distributed in all layers in papillomas. Using immunoblots and Southwestern blots, we detected abundant truncated isoforms of C/EBPalpha in the papillomas. Since differentiation of many tissues is determined by the relative amounts of different C/EBPs, our data supports a role for C/EBPs in the differentiation of squamous epithelium.


Modelling hospital disinfectant against multi-drug-resistant dry surface biofilms grown under artificial human sweat.
Dry surface biofilms (DSBs) have been found abundantly across hospital surfaces within intensive care units and may explain how nosocomial pathogens can remain virulent and persist on surfaces for extended periods. Testing standards governing the performance of disinfectant products employ planktonic models under routine growth conditions, which are known to be less tolerant than their biofilm counterpart. To evaluate biofilm models cultured under artificial human sweat (AHS), a source of nutrient expected on touch surfaces, to assess the antimicrobial performance of common cleaning agents, including a quaternary ammonium, hydrogen peroxide and active chlorine. Five single-species biofilms, using pathogenic bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis, were generated on stainless-steel substrates using a sedimentation protocol under both AHS and nutrient-rich conditions for a direct comparison of phenotypic tolerance. The biofilm models were grown over five days followed by desiccation cycles, before being submerged into the disinfectant solutions for up to 25 min. Epifluorescence (EF) microscopy using LIVE/DEAD™ stain was used to visualize microcolony viability. The results revealed biofilms cultured under AHS exhibited a greater antimicrobial tolerance and reduced speed of kill for all cleaning agents compared with the routine media; an average reduction of 72.4% vs 96.9%, respectively. EF microscopy revealed traces of viable bacteria across all coupons after disinfection indicating a potential opportunity for regrowth and recontamination. The notable difference in biocidal performance between the two growth conditions highlights potential pitfalls within current antimicrobial test standards, and the importance of accurate representation of the microbial challenge.


Filament formation in Saccharomyces cerevisiae--a review.
Many yeasts can produce filamentous elongated cells identifiable as hyphae, pseudohyphae or invasive filaments. Filament formation has been understood as a foraging response that occurs in nutrient-poor conditions. However, fusel alcohols were observed to induce filament formation in rich nutrient conditions in every yeast species examined. Fusel alcohols, e.g., 3-methyl-1-butanol (3Me-BuOH; 'isoamyl alcohol'), 2-methyl-1-propanol (isobutyl alcohol), (-)-2-methyl-1-butanol ('active amyl alcohol'), 2-phenylethanol and 3-(2-hydroxyethyl)indole (tryptophol) (the end products of leucine, valine, isoleucine, phenylalanine and tryptophan catabolism, respectively) are the end products of amino acid catabolism that accumulate when nutrients become limiting. Thus, yeast responds to its own metabolic by-products. Considerable effort was made to define the cell biological and biochemical changes that take place during 3Me-BuOH-induced filamentation. In Saccharomyces cerevisiae filaments contain significantly greater mitochondrial mass and increased chitin content in comparison with yeast-form cells. The global transcriptional response of S. cerevisiae during the early stages of 3Me-BuOH-induced filament formation has been described. Four ORFs displayed very significant (more than 10-fold) increases in their RNA species, and 12 ORFs displayed increases in transcription of more than 5-fold. The transcription of five genes (all of which encode transporters) decreased by similar amounts. Where examined, the activity of the proteins encoded reflected the transcriptional pattern of their respective mRNAs. To understand this regulation, studies were performed to see whether deletion or overexpression of key genes affects the ability to filament and invade solid YEPD medium. This has led to identification of those proteins that are essential for filament formation, repressors and those which are simply not required. It also leads to the conclusion that 3Me-BuOH-induced filament formation is not a foraging response but a response to reduced growth rate.


Hydroxocobalamins as biologically compatible donors of nitric oxide implicated in the acceleration of wound healing.
In the late 1970s, research was unfolding that implicated nitric oxide involvement in the process of vasodilation. By 1986, research culminated in the identification of nitric oxide as the endothelium-derived relaxing factor responsible for the maintenance of vascular tone, thus implicating nitric oxide as a potential wound-healing agent. Biomedical researchers involved in wound-healing research quickly embraced the utility of developing a polymeric donor of nitric oxide which would enhance the wound-healing process. Several synthetic nitric oxide donors have been developed, dubbed 'NONOates', which have achieved great success in delivering nitric oxide to wounds. However, the impact on wound healing has been ambiguous and deemed antagonistic to the immune system in some cases. The propensity for the immune system to reject 'non-self' is a major factor in evaluating the usefulness of synthetic polymeric nitric oxide donors. The necessity of natural-product nitric oxide donors is apparent when examining the complications which are possible in a synthetic delivery system. Given the affinity nitric oxide has for transition metals, and the biological availability of transition-metal-centered products in vivo, it seems logical to pursue a transition-metal nitric oxide donor which is biologically friendly. Vitamin B12a (hydroxocobalamin), a natural product, offers an ideal environment to serve as a donor of nitric oxide.


Internal motion of F-actin in 10(-6)-10(-3) s time range studied by transient absorption anisotropy: detection of torsional motion.
By means of laser flash photolysis, the transient absorption anisotropy (TAA) of the triplet probe, 5-iodoacetamide-Eosin, labeling rabbit skeletal F-actin was measured in the 10(-6)-10(-3) s time range. The TAA curve at 20 degrees C showed a relatively slow decay phase covering several hundred microseconds and a large residual anisotropy (approximately 0.1 at 2 ms). After analysis with Barkley & Zimm's formula, it was concluded that the TAA of Eosin-F-actin can be approximated by the anisotropy decay due to torsional motion of F-actin.


Empyema thoracis due to intrapleural migration of retained vascular catheter.
Intravascular retention and embolization of fragment of central venous catheters is a rare but well-documented complication of in-dwelling vascular access devices and ports. We describe the case of a 39-year-old male with fracture of the central venous catheter during removal of subcutaneous vascular access port. Over the next 3 years, the catheter fragment embolized through the pulmonary circulation and subsequently migrated into the left pleural space. He presented with empyema thoracis associated with thoracolumbar vertebral osteomyelitis. He required video-assisted thoracoscopy for retrieval of the catheter fragment, left lung decortication, and subsequent multilevel vertebral corpectomy and spine stabilization procedures.


Age-dependent changes in contractile function and passive elastic properties of myocardium from mice lacking muscle LIM protein (MLP).
Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy. So far, little is known about the time course and pathomechanisms leading to the development of the adult phenotype. We systematically analysed the contractile phenotype, myofilament calcium (Ca(2)(+)) responsiveness, passive myocardial mechanics, histology, and mRNA expression in mice aged 4 and 12 weeks. In 4-week-old animals, there was no significant difference in the force-frequency relationship (FFR) and catecholamine response of intact isolated papillary muscles between wild-type (WT) and MLP null myocardium. In 12-week-old animals, WT myocardium exhibited a significantly positive FFR, while that of MLP null mice was significantly negative, and the inotropic response to catecholamines was significantly reduced in MLP null mice. This time course of decline in contractile function was confirmed in vivo by echocardiography. Whereas at 4 weeks of age MLP null mice and WT littermates showed similar levels of SERCA2a (sarcoplasmic reticulum Ca(2+) ATPase) expression, the expression was significantly lower in 12-week-old MLP null mice compared with littermate controls. Myofilament Ca(2)(+) responsiveness was not affected by the lack of MLP, irrespective of age. Whereas in 4-week-old animals MLP null myocardium showed a trend to an increased compliance compared with the WT, myocardium of 12-week-old MLP null mice was significantly less compliant than WT myocardium. Parallel to the decrease in compliance there was an increase in fibrosis in the MLP null animals. Our data suggest that MLP deficiency does not primarily influence myocardial contractility. A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis.


The design and application of a data- and methodbase system for the Aachen Aphasia Test.
The basic components of a data- and methodbase system useful for both individual diagnosis and (group-study) research in neuropsychology are described. Such a system enables one to organize, access and evaluate large data-sets of behavioural, neuroradiological and neurological information. The most important component of the system, the data- and methodbase management system, is described in some detail. It operates on databases comprised of Aachen Aphasia Test examinations and standardized CT evaluations as well as on methodbases containing various sets of analysis routines for the psychometric evaluation of (individual) aphasia test results and the evaluation and (graphical) presentation of standardized (individual) CT lesions. Although exemplified for AAT scores the techniques and principles employed are applicable to data- and methodbase systems in general.


Evaluation of the efficacy of commercial and noncommercial tourniquets for extremity hemorrhage control in a perfused cadaver model.
Tourniquets are a critical tool in the immediate response to life-threatening extremity hemorrhage; however, the optimal tourniquet type and effectiveness of noncommercial devices remain unclear. Our aim was to evaluate the efficacy of five tourniquets in a perfused-cadaver model. This prospective study used a perfused-cadaver model with standardized superficial femoral artery injury bleeding at 700 mL/min. Five tourniquets were tested: combat application tourniquet; rapid application tourniquet system; Stretch, Wrap, And Tuck Tourniquet; an improvised triangle bandage windlass; and a leather belt. Forty-eight medical students underwent a practical hands-on demonstration of each tourniquet. Using a random number generator, they placed the tourniquets on the bleeding cadaver in random order. Time to hemostasis, time to secure devices, estimated blood loss, and difficulty rating were assessed. A one-way repeated measures analysis of variance was used to compare efficacy between the tourniquets in achieving the outcomes. The mean ± SD participant age was 25 ± 2.6 years, and 29 (60%) were male. All but one tourniquet was able to stop bleeding, but the rapid application tourniquet system had a 4% failure rate. Time to hemostasis and estimated blood loss did not differ significantly (p > 0.05). Stretch, Wrap, And Tuck Tourniquet required the longest time to be secured (47.8 ± 17.0 seconds), whereas the belt was the fastest (15.2 ± 6.5 seconds; p < 0.001). The improvised windlass was rated easiest to learn and apply, with 22 participants (46%) assigning a score of 1. Four of five tourniquets evaluated, including both noncommercial devices, effectively achieved hemostasis. A standard leather belt was the fastest to place and was able to stop the bleeding. However, it required continuous pressure to maintain hemostasis. The improvised windlass was as effective as the commercial devices and was the easiest to apply. In an emergency setting where commercial devices are not available, improvised tourniquets may be an effective bridge to definitive care.


A meta-analysis of the relationship between vaginal microecology, human papillomavirus infection and cervical intraepithelial neoplasia.
Microecology is an emerging discipline in recent years. The female reproductive tract is an important microecological region, and its microecological environment can directly affect women's cervical health. This meta-analysis aimed to analyze the effects of vaginal microecology on Human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). PubMed and Web of Science were systematically searched for eligible publications from January 2000 to December 2017. Articles were selected on the basis of specific inclusion and exclusion criteria. The design and quality of all studies were evaluated using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) with a 95% confidence interval (95% CI) were calculated. Thirteen eligible studies were selected to evaluate the association of vaginal microecology with HPV infection and CIN. The factors related to HPV infection were bacterial vaginosis (BV) (OR 2.57, 95% CI 1.78-3.71, P<0.05), Candida albicans (VVC) (OR 0.63, 95% CI 0.49-0.82, P < 0.05), Chlamydia trachomatis (CT) (OR 3.16, 95% CI 2.55-3.90, P < 0.05), and Ureaplasma urealyticum (UU) (OR 1.35, 95% CI 1.20-1.51, P < 0.05). BV was also related to CIN (OR 1.56, 95% CI 1.21-2.00, P < 0.05). This meta-analysis of available literature suggested an intimate association of vaginal microecology and HPV infection with CIN. BV, CT and UU were associated to increased HPV infection, VVC was associated to decreased HPV infection, Lactobacillus is not associated to increased HPV infection, BV was associated to increased CIN development risk. Further large-scale studies are needed to confirm our findings.


Radiology Environmental Impact: What Is Known and How Can We Improve?
The healthcare sector generates approximately 10% of the total carbon emissions in the United States. Radiology is thought to be a top contributor to the healthcare carbon footprint due to high energy-consuming devices and waste from interventional procedures. In this article, we provide a background on Radiology's environmental impact, describe why hospitals should add sustainability as a quality measure, and give a framework for radiologists to reduce the carbon footprint through quality improvement and collaboration.


[Digestives diseases associated to sickle cell anemia in Lubumbashi: epidemiological and clinical aspects].
sickle cell disease is a genetic disease with autosomal inheritance associated with haemoglobin structure abnormality which causes the formation of hemoglobin S. The purpose of our study was to collect data on digestive diseases in patients with sickle cell disease in Lubumbashi and to highlight their epidemiological and clinical features. We conducted a retrospective, descriptive, cross-sectional study at the Research Center for Sickle Cell Disease in Lubumbashi. All the records of patients on follow-up for sickle cell disease with digestive disease during our 3-year period (January 2015 to December 2017) were analyzed. Data were collected using a survey taking into account different study parameters including: age, sex, the reason for consultation, diagnosis, the type of vaso-occlusive crisis, the paraclinical examinations made, hydroxyurea treatment. out of a total of 403 medical records examined we found 206 cases (n=206) of sickle cell disease associated with digestive disease, accounting for a rate of 51,11% of patients with sickle cell disease who suffered from digestive diseases. Both sexes were represented with a slight female predominance (51.94%) and a sex ratio M/F of 0.92. The most represented age ranges 1-6 years (32.52%), the average age was 11.8 years; the standard deviation was 21.9; the extreme ages were 13 months and 38 years. The reason for consultation was dominated by fever (60,67%), abdominal pain (44.66%) and digestive disorders (30,09%). Vaso-occlusive abdominal crises were found in 65 patients (31.55%) among whom 36 had only 1 crisis, 24 had 2 crises and 5 had 3 crises. Intestinal diseases were found in 121 patients (69,41%) dominated by intestinal parasites (found in 58 patients whose collection of stool samples showed 4 parasites: Yersinia enterocolitis, Entamoeba histolytica, Giardia intestinalis and Clostridium difficile). Gastric diseases were found in 105 patients ( 50,97%) divided into peptic ulcer (45 patients) and gastritis (60 patients); biliary vesicular disease was found in 40 patients (19.41%) including vesicular lithiasis without cholecystitis (32 patients), lithiasic cholecystitis (5 patients) and lithiasis in the main biliary tract (3 cases); there was 1 single case diagnosed with acute pancreatitis. The most common associated diseases in our study were respiratory diseases (169 cases;82,03%), oto-rhino-laryngological diseases (157 cases;76.21%), bony, vaso-occlusive crises (146 cases; 70,87%), urogenital diseases (64 cases; 31.06%) and malaria (51 patients; 24.75%). Hepatic diseases and diseases of the spleen were found in 18 cases (8.73%) and 47 cases (22,81%) respectively. Ultrasound was requested in 79 patients but only 31 of them underwent it because of the lack of financial means (it costs 20 U.S. dollars). In the case of clinically obvious splenomegaly, the search for Howell-Jolly bodies was requested in 23 patients but it was only performed in 2 patients because it costs 10 U.S. dollars). Routine blood count, hemoglobin, hematocrit, inflammatory assessment and thick drop examination were performed in all our patients but liver assessment, tests done on stool samples, urine test were recommended based on patient's complaint. Out of 206 patients, only 60 were under hydroxyurea treatment (29,16%). digestive diseases are common in patients with sickle cell disease and account for almost half of patients with diagnosed sickle cell disease. Unfortunately, best management is limited by poverty leading to less very useful paraclinical examinations in patients with digestive diseases resulting from sickle cell disease.


Can early introduction of specialized palliative care limit intensive care, emergency and hospital admissions in patients with severe and very severe COPD? a randomized study.
COPD is a progressive lung disorder with rates of mortality between 36-50%, within 2 years after admission for an acute exacerbation. While treatment with inhaled bronchodilators and steroids may partially relieve symptoms and oxygen therapy may prolong life, for many patients the course of the disease is one of inexorable decline. Very few palliative care intervention studies are available for this population. This trial seeks to determine the effectiveness of the introduction of specialized palliative care on hospital, intensive care unit and emergency admissions of patients with severe and very severe COPD. The study is a three year single centre, randomized controlled trial using a 2 arms parallel groups design conducted in a tertiary center (University Hospitals; Geneva). For the intervention group, an early palliative care consultation is added to standard care; the control group benefits from standard care only. Patients with COPD defined according to GOLD criteria with a stage III or IV disease and/or long term treatment with domiciliary oxygen and/or home mechanical ventilation and/or one or more hospital admissions in the previous year for an acute exacerbation are eligible to participate. Allocation concealment is achieved using randomisation by sealed envelopes. Our sample size of 90 patients/group gives the study a 80% power to detect a 20% decrease in intensive care unit and emergency admissions--the primary endpoint. All data regarding participants will be analysed by a researcher blinded to treatment allocation, according to the "Intention to treat" principle. Given the trends toward aggressive and costly care near end-of-life among patients with COPD, a timely introduction of palliative care may limit unnecessary and burdensome personal and societal costs, and invasive approaches. The results of this study may provide directions for future palliative care interventions in this particular population. This trial has been registered at clinicaltrials.gov under NCT02223780.


Improving the Carprofen Solubility: Synthesis of the Zn2Al-LDH Hybrid Compound.
The development of efficient strategies for drug delivery is considerably desired. Indeed, often several issues such as the drug solubility, the control of the drug release rate, the targeted delivery of drugs, the drug bioavailability, and the minimization of secondary effects still present great obstacles. Different methodologies have been proposed, but the use of nano-hybrids compounds that combine organic and inorganic substances seems particularly promising. An interesting inorganic host is the layered double hydroxide (LDH) with a sheets structure and formula [M2+1-x M3+x (OH)2](An-)x/n yH2O (M2+ = Zn, Mg; M3+ = Al; An- = nitrates, carbonates, chlorides). The possibility to exchange these counterions with drug molecules makes these systems ideal candidates for the drug delivery. In this article, we synthesize by co-precipitation method the hybrid compound Carprofen-Zn2Al-LDH. Carprofen, a poorly soluble anti-inflammatory drug, could also benefit of the association with a natural antacid such as LDH, to reduce the gastric irritation after its administration. Through X-ray diffraction and Fourier-transformed infrared spectroscopy (FT-IR), we could verify the effective drug intercalation into LDH. The dissolution tests clearly demonstrate a significant improvement of the drug release rate when carprofen is in the form of hybrid compound.


Defective cerebellar ryanodine receptor type 1 and endoplasmic reticulum calcium 'leak' in tremor pathophysiology.
Essential Tremor (ET) is a prevalent neurological disease characterized by an 8-10 Hz action tremor. Molecular mechanisms of ET remain poorly understood. Clinical data suggest the importance of the cerebellum in disease pathophysiology, and pathological studies indicate Purkinje Cells (PCs) incur damage. Our recent cerebellar cortex and PC-specific transcriptome studies identified alterations in calcium (Ca2+) signaling pathways that included ryanodine receptor type 1 (RyR1) in ET. RyR1 is an intracellular Ca2+ release channel located on the Endoplasmic Reticulum (ER), and in cerebellum is predominantly expressed in PCs. Under stress conditions, RyR1 undergoes several post-translational modifications (protein kinase A [PKA] phosphorylation, oxidation, nitrosylation), coupled with depletion of the channel-stabilizing binding partner calstabin1, which collectively characterize a "leaky channel" biochemical signature. In this study, we found markedly increased PKA phosphorylation at the RyR1-S2844 site, increased RyR1 oxidation and nitrosylation, and calstabin1 depletion from the RyR1 complex in postmortem ET cerebellum. Decreased calstabin1-RyR1-binding affinity correlated with loss of PCs and climbing fiber-PC synapses in ET. This 'leaky' RyR1 signature was not seen in control or Parkinson's disease cerebellum. Microsomes from postmortem cerebellum demonstrated excessive ER Ca2+ leak in ET vs. controls, attenuated by channel stabilization. We further studied the role of RyR1 in tremor using a mouse model harboring a RyR1 point mutation that mimics constitutive site-specific PKA phosphorylation (RyR1-S2844D). RyR1-S2844D homozygous mice develop a 10 Hz action tremor and robust abnormal oscillatory activity in cerebellar physiological recordings. Intra-cerebellar microinfusion of RyR1 agonist or antagonist, respectively, increased or decreased tremor amplitude in RyR1-S2844D mice, supporting a direct role of cerebellar RyR1 leakiness for tremor generation. Treating RyR1-S2844D mice with a novel RyR1 channel-stabilizing compound, Rycal, effectively dampened cerebellar oscillatory activity, suppressed tremor, and normalized cerebellar RyR1-calstabin1 binding. These data collectively support that stress-associated ER Ca2+ leak via RyR1 may contribute to tremor pathophysiology.


Analgesic use and chronic renal disease in patients with headache.
The pattern of analgesic use, abuse and incidence of analgesic-associated nephropathy in 79 patients with chronic headache was studied. Sixty-eight of these patients had migraine. Most patients had consumed a combination of analgesics (81%) while 19% had taken single analgesics for their headache. Nonsteroidal anti-inflammatory drugs were the most commonly used analgesics (96.2%) followed by paracetamol (70.9%) and aspirin, phenacetin and caffeine compounds (5.1%). Mefenamic acid was the commonest nonsteroidal anti-inflammatory drug consumed (97.4%). Analgesic abuse which was defined as a minimum total of 1 kg of analgesics such as paracetamol or aspirin, phenacetin and caffeine compounds or 400 capsules/tablets of nonsteroidal anti-inflammatory drugs was noted in 65 patients. Nonsteroidal anti-inflammatory drugs were the most commonly abused analgesics (89.2%) followed by paracetamol (38.5%). Forty-five of the 65 analgesic abusers had an intravenous urogram or ultrasound performed and renal papillary necrosis was documented in one patient. Three (4.6%) of the analgesic abusers had mildly raised serum creatinine levels. Mild proteinuria of less than 1 gm/litre was present in 27.7% of abusers. In conclusion, although analgesic use and abuse is common in patients with chronic headache, the short term incidence of analgesic-associated nephropathy (2.2%) and renal impairment (4.6%) was low. Prolonged observations will be necessary to ascertain the safety of these drugs for long term use.


First-line managers' experience of the use of audit and feedback cycle in specialist mental health care: A qualitative case study.
Audit and feedback was the main strategy to facilitate implementation of The National Guideline for Persons with Concurrent Substance Use Disorders and Mental Disorders in specialist mental health services. Studies have shown that leadership support contributes to implementation success. The aim of the study was to explore how first-line managers in a District Psychiatric Centre experienced using audit and feedback cycle. The study had a qualitative case study design with individual interviews with five first-line managers from a District Psychiatric Centre in Norway. Qualitative content analysis was conducted. First-line managers were positive to contribute to better practice for the patient group and apply available tools. Four themes emerged: 1) Lack of endurance, where first-line managers saw their role as being process leaders, but failed to persist, 2) Lack of support in the process, where first-line managers called for a stronger organisational focus 3) Lack of ownership, where first-line managers felt the process was imposed on them, and 4) Lack of leader autonomy, where first-line managers seemed insecure about their role between professional leadership and own management. First-line managers were not sufficiently experienced or equipped to solve the implementation process satisfactorily. They were torn between different commitments, without the autonomy to act as process drivers or facilitators, and without taking the necessary leadership role. The potential impact of the use of audit and feedback may thus not be fully realized, in part, because of limited organisational support and capacity to respond effectively.


Chemotherapy of trypanosomiases and leishmaniasis.
New formulations, therapeutic switching of the established drugs amphotericin B and paromomycin, and the serendipitous discovery of miltefosine have markedly improved leishmaniasis chemotherapy in the past 21 years. The situation for the two trypanosomiases has been less encouraging. Apart from the introduction of eflornithine for the treatment of late-stage human African trypanosomiasis, with its serious limitations in terms of cost and difficulty of administration, no new drugs have been incorporated into the chemotherapeutic arsenal in the past 25 years, despite important advances in knowledge of the biology of the etiological agents and the pathophysiology of these diseases. In the case of Chagas disease, several classes of compound that target the validated biochemical pathways of the parasite (e.g. inhibitors of sterol biosynthesis and cysteine proteases) are in the pipeline. With the availability of complete genome sequences for all three pathogens, and methods for rapid validation of targets, it is hoped that much-needed amelioration will occur soon. Financial constraints continue to represent a major hurdle to drug development. However, the appearance of not-for-profit product-development partnerships offers a new paradigm for bringing new drugs to patients.


Stimulation of duodenal and ileal absorption of phosphate in the chick by low-calcium and low-phosphorus diets.
The intestinal absorption of phosphate has been studied in vivo in the chick using ligated segments of duodenum and ileum. Feeding diets low in calcium (0.1%) and/or low in phosphorus (0.25%) caused an increase in the absorption of phosphate from both the duodenum and ileum. These changes are consistent with a putative increase in the renal production and mucosal uptake of 1,25-dihydroxycholecalciferol.


[Update on computer- and mechatronic-assisted head and neck surgery in Germany].
A consequence of the ongoing advances in medical navigation is the development of so-called mechatronic assistant systems. Up to now, medical navigation had been used only for additional intrasurgical orientation. But improvements in accuracy in imaging and medical navigation can exceed the surgeon's possible manual accuracy of surgical manipulation. In such cases, mechatronic assistant systems can supplement certain surgical procedures in order to obtain the required precision, such as for positioning of implants. The development and possible use of such mechatronic assistant systems in the head and neck, as well as improvements in the accuracy of medical navigation, are the focus of several working groups. For coordinating and adapting the various research projects, different research groups were called to present their current projects and results in the context of ASKRA (working group for skull-base and craniofacial surgery of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery) workshops at the German Society for Computer- and Robot-Assisted Surgery (CURAC) convention on 14 October 2006 in Hanover. Different projects were presented, with topics including navigated controlled assistant systems for the frontal and lateral skull base, possibilities for sonographic-induced bone measurement, and requirements for high-precision surgery of the skull base.


Colour Stability, Fatty Acid Profile, and Lipid Oxidation in Meat Stored in Modified Atmosphere Packaging from Light Lambs Fed with Concentrate with Carob Pulp (Ceratonia siliqua L.).
There is a growing interest in using by-products rich in polyphenols, such as carob pulp (Cp, Ceratonia siliqua L.), as a dietary source of antioxidants for animals. This study assesses the effects of including Cp in lambs' diet and meat display time (0, 7, 9, and 11 days) in modified atmosphere packaging on meat colour, fatty acid (FA) composition, tocopherol levels, and lipid oxidation values in the Semimembranosus muscle of 40 light lambs. The lambs were fed with concentrates supplemented with increasing Cp levels (0, 150, and 300 g/kg) for 45 days before slaughter. Metmyoglobin (MMb) and malondialdehyde (MDA) contents increased linearly with display time (p < 0.05), regardless of diet (p > 0.05). At 11 days of display, MMb (28 ± 0.8%) and MDA (0.6 ± 0.1 mg MDA/kg of meat) contents remained within the acceptable limits. The α-tocopherol content was lower in the 30% Cp group and meat (p < 0.05). Total saturated and monounsaturated FA contents (934 ± 64 and 823 ± 65 mg/100 g of meat, respectively) did not differ significantly among the groups. However, the meat from lambs fed with 30% Cp showed reduced levels of branched-chain FAs, while polyunsaturated FAs increased (p < 0.05) compared to the control lambs. The inclusion of Cp in the lamb's diet, up to 30%, did not lead to meat deterioration and improved certain quality parameters, including a healthier FA profile. These findings highlight Cp's potential as an alternative antioxidant source in animal diets.


The synthesis of alternative diketopiperazines as potential RGD mimetics.
Alternative RGD mimetics-with the exception of glycine-c(Arg-Asp) 1, c(Arg-Glu) 2 and c[Arg-Asp(Phe-OH)] 3 were synthesized. The DKPs were prepared on solid phase with orthogonal protection allowing further derivatization in solution. During solution phase cyclization in NH(3)/methanol, the side chain benzyl ester group of H-Arg(Tos)-Asp(OBzl)-OMe and H-Arg(Tos)-Glu(OBzl)-OMe suffer transesterification, while beta-t-butyl or beta-cyclohexyl esters are stable under the same conditions. In spite of the simple structure, all compounds bind selectively to the alpha(v)beta(3) integrin receptor, 3 showing the highest affinity with an IC(50) value of 0.74 microM value. On the other hand only 3 binds with measurable activity to the alpha(IIb)beta(3) receptor (IC(50) 159 microM). The binding affinities seem to be in accordance with the distances between the arginine guanidino and the aspartic acid carboxyl group in extended conformation determined by semiempirical geometry optimization.


Origins of hyperphenylalaninemia in burn patients.
Plasma phenylalanine concentrations were measured on the seventh postburn day in patients with burn surface areas ranging from 1 to 39%. Hepatic function (glutamate-pyruvate transaminase, prothrombin time) and protein breakdown (nitrogen balance, urine 3-methylhistidine/creatinine ratio) were evaluated in parallel. Plasma phenylalanine concentrations in patients with normal hepatic function and those with hepatic failure were similar. A correlation was shown between phenylalaninemia and nitrogen balance for all patients but phenylalaninemia only correlated with the urine 3-methyl-histidine/creatinine ratio in patients with burn surface areas under 20%. Taken as a whole, the data suggest that the determination of plasma phenylalanine concentration is a valuable test to assess the nitrogen balance in burn patients. This test, when performed on day 7, is particularly relevant in patients with normal hepatic function and either slight or moderate burn injury.


Determination of histamine in canned tuna by molecularly imprinted polymers-surface enhanced Raman spectroscopy.
We introduce a rapid, cost effective and reliable approach to determine histamine level in canned tuna. Molecularly imprinted polymers (MIPs) were synthesized as artificial antibodies towards histamine by utilizing the interaction between histamine and a functional monomer (methacrylic acid) to impress specific binding sites on polymer particles after polymerization. Polyvinyl chloride (PVC) was used to immobilize the MIPs, yielding a MIPs-PVC film that functioned as a recognition element to specifically separate histamine from tuna extract. A gold colloid solution served both as an eluting solvent to extract histamine from MIPs-PVC film and furnish a substrate for surface enhanced Raman spectroscopy (SERS) detection of histamine signals. Principal component analysis together with a partial least square regression (PLSR) model (R(2) = 0.947, RMSECV = 3.526) verified the reliability of MIPs-PVC-SERS approach for the detection and spectral analysis of histamine. Linear regression models were also constructed to relate the intensity of different histamine SERS bands with the corresponding spiking levels. One such model (using a band at 1576 cm(-1)) performed slightly better in predicting histamine content in tuna than the PLSR model. We conclude that our new MIPs-PVC-SERS approach can rapidly and reliably determine histamine at levels from 3 to 90 ppm in canned tuna meat.


Prenatal assessment of foot deformity.
Congenital talipes equinovarus (CTEV) and other skeletal abnormalities can be diagnosed prenatally by ultrasound scan. If diagnosed, clinicians should be cautiously optimistic with the parents, particularly if the talipes diagnosed is isolated and not associated with other foetal abnormalities. There is no correlation between the prenatal appearance of the foot and the state of the foot at birth, nor with the necessity for surgical intervention.


Caring for dying patients--what are the attitudes of medical students?
Students entering medical school today will encounter an ageing population and a higher incidence of patients with terminal and life threatening illness. This study was carried out to determine the attitudes of pre-clinical medical students towards the care of patients for whom a cure is not possible. All students were invited to complete a 23-item questionnaire prior to any teaching in palliative care. Of the 186 students who participated in the study, 151 (79%) completed the pre-teaching questionnaire (males=59; females 90; median age 20 years; range 19-27]. Attitudes towards chronically ill and dying patients were generally positive. When comparing age with attitudes it was found that increasing age was associated with a more positive view of caring for patients with chronic or terminal illness, a more positive view of listening to patients reminisce and a more positive view of patients dying at home. Caring for patients at the end of life can be one of the most rewarding aspects of being a doctor. This study suggests that the majority of medical students have a positive attitude towards patients with chronic and terminal illness-the trend for encouraging older students to enter medicine may be an influencing factor.