Strategies Employed to Evade the Host Immune Response and the Mechanism of Drug Resistance in Mycobacterium tuberculosis: In Search of Finding New Targets.
The partial effectiveness of the host immune response to M. tuberculosis drives bacteria into a latent state, but it is difficult to eliminate the bacteria completely. Usually, this latent condition of M. tuberculosis is reversible, and reactivation of tuberculosis is the leading cause of the majority of transmission. A number of studies performed on animal models and humans have not yet provided a detailed understanding of the mechanisms or correlates of immunity of M. tuberculosis infection or why there is a significant immunity failure to remove the pathogen. Moreover, the mechanism of resistance involved in drug-resistant M. tuberculosis leads to the emergence of strains of bacteria that show significant resistance to the majority of anti-tuberculosis drugs. We have also provided the recent findings and trends regarding the development of new drug molecules to treat drug and multidrug-resistant tuberculosis and the advancements in immunotherapy in the treatment of drug-resistant tuberculosis. This article provides an in-depth and critical analysis of various strategies employed by the drug-resistant M. tuberculosis to escape the host immune response. This bacterium persists in the host for a longer period of time and leads to the development of tuberculosis infection. Furthermore, we also discussed the new targets for the effective treatment of drug-resistant tuberculosis.


The effect of local resource availability and clonal integration on ramet functional morphology in Hydrocotyle bonariensis.
Within a physiologically integrated clone, the structure and functioning of an individual ramet is determined by: 1) the response of that ramet to its local environment and 2) its response to resource integration within the clone. In a multifactorial experiment, Hydrocotyle bonariensis ramets were grown in limiting resource environments with and without the benefit of basipetal resource movement from another branch of the clone. Ramets were analyzed for their morphological responses to variation in local light, water and nitrogen availability and to the superimposed effect of resource integration on these conditions. The expression of ramet morphology, from induction to development, was highly plastic in response to variable local resource availability. Resource integration changed a ramet's local response in a variety of ways depending on the resource(s) being translocated and the character involved. Among leaf characteristics (leaf weight, petiole height, blade area), resource translocation into the shade resulted in an enhancement of the local response. Similarly, the translocation of nitrogen and water generally increased clonal proliferation and sexual reproduction among ramets. In contrast, the translocation of water reversed the effect of local low water conditions on ramets by inhibiting root production. Some characters such as internode distance and leaf allometry were unaffected by integration. The maintenance of connections between ramets as a Hydrocotyle clone expands allows for resource sharing among widely separated ramets and can result in an integrated morpological response to a resource environment that is patchy in time and space.


Spectral properties of Eigen evolution matrices.
Eigen has employed deterministic kinetic-like equations to describe macromolecular replication and mutation leading to selection. The solutions to these equations and their physically interesting properties depend upon the spectrum of a type of matrix appearing in those equations. Below we explicitly solve for the spectrum of a fairly general class of such matrices. These solutions are obtained recursively for equations describing macromolecules of any length v.


Revealing the mechanism of tissue damage due to tobacco use: finally, a smoking gun?
This commentary highlights the article by Li et al that presents a compelling case for a mechanism by which tobacco smoke extract (TSE) induces damage to the extracellular matrix, a key element in the pathogenesis of tobacco-related disease.


Studies on heavy metal removal efficiency and antibacterial activity of chitosan prepared from shrimp shell waste.
Chitosan, a natural biopolymer composed of a linear polysaccharide of α (1-4)-linked 2-amino 2-deoxy β-D glucopyranose was synthesized by deacetylation of chitin, which is one of the major structural elements, that forms the exoskeleton of crustacean shrimps. The present study was undertaken to prepare chitosan from shrimp shell waste. The physiochemical properties like degree of deacetylation (74.82 %), ash content (2.28 %), and yield (17 %) of prepared chitosan indicated that that shrimp shell waste is a good source of chitosan. Functional property like water-binding capacity (1,136 %) and fat-binding capacity (772 %) of prepared chitosan are in total concurrence with commercially available chitosan. Fourier Transform Infra Red spectrum shows characteristic peaks of amide at 1,629.85 cm-1 and hydroxyl at 3,450.65 cm-1. X-ray diffraction pattern was employed to characterize the crystallinity of prepared chitosan and it indicated two characteristic peaks at 10° and 20° at (2θ). Scanning electron microscopy analysis was performed to determine the surface morphology. Heavy metal removal efficiency of prepared chitosan was determined using atomic absorption spectrophotometer. Chitosan was found to be effective in removing metal ions Cu(II), Zn(II), Fe(II) and Cr(IV) from industrial effluent. Antibacterial activity of the prepared chitosan was also determined against Xanthomonas sp. isolated from leaves affected with citrus canker.


Relation between platelet indices and branch retinal vein occlusion in hypertensive patients.
Branch retinal vein occlusion (BRVO) is the second most common retinal vascular disease after diabetic retinopathy. To date, the studies were unable to elucidate the mechanism of the thrombosis leading to the entity; particularly the relation between thrombocyte aggregation and retinal vein occlusion is still unclear. Mean platelet volume (MPV) is a determinant of rate of platelet production and activation, both of which are indices of function of platelets. The relation between MPV and BRVO has not been studied before. The aim was to evaluate MPV in BRVO. Forty patients were included in the study. Forty six age and sex matched hypertensive volunteers were recruited as the control group. MPV values were significantly higher in BRVO patients compared with the control subjects (8.01 ± 0.79 vs 7.52 ± 0.32 fL, respectively; P < 0.001). MPV is significantly higher in patients hypertensive BRVO patients and further investigations regarding its potentially use as a prognostic biomarker in patients with BRVO are needed.


Use of formalin-fixed and paraffin-embedded tissues for diagnosis and therapy in routine clinical settings.
Formalin-fixed and paraffin-embedded (FFPE) tissues are used routinely everyday in hospitals world-wide for histopathological diagnosis of diseases like cancer. Due to formalin-induced cross-linking of proteins, FFPE tissues present a particular challenge for proteomic analysis. Nevertheless, there has been recent progress for extraction-based protein analysis in these tissues. Novel tools developed in the last few years are urgently needed because precise protein biomarker quantification in clinical FFPE tissues will be crucial for treatment decisions and to assess success or failure of current and future personalized molecular therapies. Furthermore, they will help to conceive why only a subset of patients responds to individualized treatments. Reverse phase protein array (RPPA) is a very promising new technology for quick and simultaneous analysis of many patient samples allowing relative and absolute protein quantifications. In this chapter, we show how protein extraction from FFPE tissues might facilitate the implementation of RPPA for therapy decisions and discuss challenges for application of RPPA in clinical trials and routine settings.


Ajoene, an experimental anti-leukemic drug: mechanism of cell death.
The organosulfur compound ajoene, a constitutent of garlic, has been shown to induce apoptosis in a leukemic cell line as well as in blood cells of a leukemic patient. The mechanisms of action of ajoene, however, are unknown. The present study aims to characterize the molecular events leading to ajoene-triggered apoptosis. We show here that ajoene (20 microM) leads to a time-dependent activation of caspase-3-like activity as well as to the proteolytic processing of procaspase-3 and -8. Activation of caspases was necessary for ajoene-induced apoptosis since the broad-range caspase inhibitor zVAD-fmk completely abrogated ajoene-mediated DNA fragmentation. Although the initiator caspase-8 was activated, the CD95 death receptor was not involved in death signaling since the HL-60 clone used was shown to express a functionally inactive CD95 receptor. Furthermore, ajoene induced the release of cytochrome c, which was not inhibited by zVAD-fmk indicating that cytochrome c release precedes caspase activation. Ajoene also led to a dissipation of the mitochondrial transmembrane potential. Overexpression of Bcl-x(L) clearly diminished ajoene-induced caspase activation as well as apoptosis. These results indicate that apoptosis in leukemia cells triggered by ajoene is based on the activation of a mitochondria-dependent caspase cascade which includes also the activation of the initiator caspase-8.


Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function.
Age-related decline in circulating levels of insulin-like growth factor (IGF)-1 is associated with reduced cognitive function, neuronal aging, and neurodegeneration. Decreased mitochondrial function along with increased reactive oxygen species (ROS) and accumulation of damaged macromolecules are hallmarks of cellular aging. Based on numerous studies indicating pleiotropic effects of IGF-1 during aging, we compared the central and peripheral effects of circulating IGF-1 deficiency on tissue mitochondrial function using an inducible liver IGF-1 knockout (LID). Circulating levels of IGF-1 (~ 75%) were depleted in adult male Igf1f/f mice via AAV-mediated knockdown of hepatic IGF-1 at 5 months of age. Cognitive function was evaluated at 18 months using the radial arm water maze and glucose and insulin tolerance assessed. Mitochondrial function was analyzed in hippocampus, muscle, and visceral fat tissues using high-resolution respirometry O2K as well as redox status and oxidative stress in the cortex. Peripherally, IGF-1 deficiency did not significantly impact muscle mass or mitochondrial function. Aged LID mice were insulin resistant and exhibited ~ 60% less adipose tissue but increased fat mitochondrial respiration (20%). The effects on fat metabolism were attributed to increases in growth hormone. Centrally, IGF-1 deficiency impaired hippocampal-dependent spatial acquisition as well as reversal learning in male mice. Hippocampal mitochondrial OXPHOS coupling efficiency and cortex ATP levels (~ 50%) were decreased and hippocampal oxidative stress (protein carbonylation and F2-isoprostanes) was increased. These data suggest that IGF-1 is critical for regulating mitochondrial function, redox status, and spatial learning in the central nervous system but has limited impact on peripheral (liver and muscle) metabolism with age. Therefore, IGF-1 deficiency with age may increase sensitivity to damage in the brain and propensity for cognitive deficits. Targeting mitochondrial function in the brain may be an avenue for therapy of age-related impairment of cognitive function. Regulation of mitochondrial function and redox status by IGF-1 is essential to maintain brain function and coordinate hippocampal-dependent spatial learning. While a decline in IGF-1 in the periphery may be beneficial to avert cancer progression, diminished central IGF-1 signaling may mediate, in part, age-related cognitive dysfunction and cognitive pathologies potentially by decreasing mitochondrial function.


Role of aqueous phase composition and hydrophilic emulsifier type on the stability of W/O/W emulsions.
Double W1/O/W2 emulsions can act as fat substitutes in food matrices, although synthetic emulsifiers are commonly used due to their inherent instability and susceptibility to coalescence. In order to guarantee the stability of the W/O interface, the synthetic emulsifier polyglycerol polyricinoleate (PGPR - 4.5% w/w) was used. However, the replacement of chemically synthesized ingredients by natural alternatives has been extensively pursued in food applications. In this sense, whey protein isolate (WPI) and sodium caseinate (SC) were used to stabilize the external aqueous phase (W2) of water-in-oil-in-water double emulsions (W1/O/W2), in addition to Tween 80 that was used as a control. The composition of the internal aqueous phase and its effects on the double emulsion were studied by the addition of sodium chloride (0.2% w/w NaCl), gallic acid (0.5% w/w GA) or a GA/NaCl mixture (0.5% / 0.2% w/w). The effect of these different hydrophilic components was evaluated from measurements of droplet size, viscosity, ζ potential, interfacial tension and kinetic stability. SC-stabilized W/O/W emulsions showed better kinetic stability than WPI- and T80-systems. These results can be attributed to the initial droplet size (SC < T80 < WPI) and viscosity of the emulsions (SC < T80 < WPI). SC is a more flexible and unfolded protein that can quickly adsorb and rearrange at the interface, favoring the formation of smaller droplets and limiting the migration of inner water droplets to the outer phase. In addition to smaller droplets, the addition of SC (8% w/w) to the external aqueous phase promoted an increase in the viscosity of bulk systems, which reduced the destabilization rates by creaming and coalescence. All W/O/W systems containing NaCl in the inner aqueous phase presented greater kinetic stability during 7 days of storage. Although the addition GA was less efficient to stabilize double emulsions compared to NaCl, this phenolic compound reduced the interfacial tension, favoring the formation of WPI- and T80-droplets with smaller diameters. However, the use of GA/NaCl blend improved the stability and functionally of W/O/W double emulsions. We concluded that the type of hydrophilic emulsifier, the properties of the inner water droplets and the viscosity of phases influenced the droplet size, viscosity and kinetic stability of double emulsions. This work provides a better understanding of how composition influences the properties of double emulsions and how it can be used to design W/O/W emulsions as fat substitutes in more complex food systems.


Elevation of plasma gastrin and pancreatic polypeptide by electrical vagal stimulation in sheep: effects of sequential stimulation.
Gastrin and pancreatic polypeptide (PP) are released into the circulation by vagal stimulation. The individual effects of the anterior and posterior vagal trunks on the release of these peptides are unknown. Four sheep were anaesthetized and studied acutely: both vagi were dissected at the hiatus and the trunks divided. In two sheep, the distal ends of the anterior trunks were stimulated for 5 min with an 8 V, 1 ms impulse at 10 Hz. After 1 h the posterior trunks were stimulated similarly. In the other two sheep, the posterior trunk was stimulated and after 1 h the anterior vagal trunk was stimulated. The anterior and posterior trunk equally stimulated the release of both gastrin and PP in four animals. The second stimulation in these four animals resulted in an 18-fold greater integrated response of gastrin and 20-fold greater response of PP. This potentiation to the second stimulus was observed in further experiments even when the same trunk, posterior or anterior, was stimulated twice. The similarity of influence of the anterior and posterior trunks for the release of PP suggests the existence of mechanisms for vagally stimulated PP release other than branches direct from the vagal trunks.


Regulatory mechanisms underlying endoplasmic reticulum stress involvement in the development of gestational diabetes mellitus entail the CHOP-PPARα-NF-κB pathway.
We investigated the proinflammatory functions of endoplasmic reticulum stress and peroxisome proliferator-activated receptor α (PPARα) in the development of gestational diabetes mellitus (GDM) and their relationship in regulating inflammation in GDM. This study was performed on placentas of normal pregnant women, women with GDM, and HTR8 cells. Transmission electron microscopy, immunohistochemistry, Western blot analysis, and RT-PCR were performed to analyze ERS and PPARα expression on both normal and GDM pregnancy placentas. ELISA was performed to analyze inflammatory biomarkers. To generate models of the GDM-like state, placentas of normal pregnancy were treated with LPS and polyinosinic-polycytidylic acid (poly [I:C]). TG, CHOP plasmid, and CHOP siRNA were assessed as to their regulation of HTR8 cells to discern the relationship between ERS and PPARα in regulating the inflammation associated with GDM. ERS was elevated in GDM placentas, induced the secretion of IL-6 and TNF-α, and attenuated the expression of GLUT-4. PPARα was diminished in GDM placentas and inhibited the inflammatory responses via the NF-κB nuclear-transport process. 4-PBA reduced CHOP and augmented PPARα, and it decreased IL-6 and TNF-α in our GDM-like explant. However, with both 4-PBA and MK886 treatment, we noted no significant difference in CHOP expression. The level of PPARα was reduced, and that of NF-κB p65 in the nucleus was elevated with TG treatment in the HTR8/Svneo. Knockdown of CHOP increased PPARα and reduced NF-κB p65, while expression of PPARα declined, and that of NF-κB p65 rose with the application of CHOP when HTR8 cells were treated with TG. ERS contributes to the pathophysiology of GDM in pregnancy via the CHOP-PPARα-NF-κB-signalling pathway by inducing aberrant activation of inflammation and insulin resistance.


Production of multilamellar, small unilamellar and reverse-phase liposomes containing house dust mite allergens. Potential adjuvants in the immunotherapy of allergic disease.
The capacity of multilamellar (MLV), small unilamellar (SUV) and reverse-phase vesicle (REV) liposomes to incorporate house dust mite allergens has been studied. All three liposome preparations entrapped mite proteins with efficiencies of 36% (SUV), 29% (MLV) and 14% (REV). MLV incorporated the complete range of proteins contained in mite extracts with apparent molecular weights ranging from 14,000 to greater than 67,000 as judged by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, several proteins with apparent molecular weights (MW) of 16,000, 36,000 and 43,000 were excluded from the REV and SUV. Immunoblotting analysis using a serum pool prepared from mite allergic individuals showed that whereas the whole spectrum of allergens was incorporated into the MLV, a MW 43,000 allergen was excluded from the REV and SUV. The exclusion of these mite components is probably a function of the relatively prolonged exposure of the original extract to organic solvent in the preparation of the REV and SUV liposomes.


The release of 3H-1-methyl-4-phenylpyridinium from bovine adrenal chromaffin cells is modulated by somatostatin.
Besides cholinergic regulation, catecholamine secretion from adrenal chromaffin cells can be elicited and/or modulated by noncholinergic neurotransmitters and hormones. This study was undertaken to investigate the influence of somatostatin and octreotide on [3H]MPP+ secretion evoked by KCl or cholinergic agents, from bovine adrenal chromaffin cells. The release of [3H]MPP+ was markedly increased by excess KCl (50 mM), acetylcholine (50 microM-10 mM) and by the nicotinic agonists, nicotine (5-100 microM) and 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP, 10-100 microM), but not by the muscarinic agonist, pilocarpine (10-100 microM). Acetylcholine-evoked release of [3H]MPP+ from these cells was mainly mediated by nicotinic receptors: a) nicotine and DMPP stimulated the release of [3H]MPP+, b) a nicotinic antagonist, hexamethonium, markedly blocked the acetylcholine-evoked response and c) pilocarpine was devoid of effect on [3H]MPP+ secretion. At all concentrations tested, somatostatin and octreotide interfered neither with [3H]MPP+ basal release nor with KCl-induced release of [3H]MPP+. However, somatostatin (0.01-0.3 microM) increased the release of [3H]MPP+ induced by a high concentration of acetylcholine (10 mM). Octreotide (1-10 microM) had no effect. These results, showing that somatostatin potentiates acetylcholine-induced [3H]MPP+ release, support the hypothesis that somatostatin may increase the release of catecholamines from adrenal medullary cells.


Acute effects of thoracolumbar fascia release techniques on range of motion, proprioception, and muscular endurance in healthy young adults.
This study investigates the acute effects of Graston and myofascial release on thoracolumbar fascia (TLF) on lumbar range of motion (ROM), lumbar and cervical proprioception, and trunk muscle endurance in healthy young adults. Twenty-four healthy young individuals were included in the study. Individuals were randomly divided into two groups as Graston technique (GT) (n = 12) and myofascial release (MFR) (n = 12). GT group received a fascial treatment with a graston instrument and the MFR group (n = 12) received manual myofascial treatment. Both techniques were applied for 10 min and as a single session. Lumbar ROM (goniometer), lumbar proprioception (digital inclinometer), cervical proprioception (CROM device), and trunk muscle endurance (with McGill Endurance Test) were evaluated before and after treatment. Age, gender and body mass index of individuals in both groups were similar (p > 0.05). In both GT and MFR groups, an increase in ROM in the flexion direction (p < 0.05) and a decrease in the angle of deviation in proprioception in the flexion direction were determined (p < 0.05). Neither technique had a significant effect on cervical proprioception and trunk muscle endurance (p > 0.05). In addition, no difference was found between the effectiveness of Graston and myofascial release (p > 0.05). This study showed that Graston and myofascial release applied to TLF in healthy young adults effectively improve lumbar ROM and proprioception in the acute period. Considering these results, both Graston and myofascial release can be used to provide elasticity of TLF and improve proprioceptive return.


RNF220 mediates K63-linked polyubiquitination of STAT1 and promotes host defense.
STAT1 is a master regulator that orchestrates type 1 and 2 interferon (IFN)-induced IFN-stimulated gene (ISG) expression. The mechanisms by which STAT1 is phosphorylated and activated upon IFN signaling remain elusive. Our work demonstrated that ubiquitination of STAT1 mediated by the E3 ligase RNF220 contributed significantly to STAT1 activation and innate immune responses. Rnf220 gene deficiency resulted in the downregulation of IFN signaling and decreased expression of ISGs in response to type 1 and 2 IFNs stimulation and Acinetobacter baumannii and HSV-1 infection. Mechanistically, RNF220 interacted with STAT1 and mediated the K63-linked polyubiquitination of STAT1 at residue K110, which promoted the interaction between STAT1 and the kinase JAK1. The expression of RNF220 was induced by pathogenic infection and IFN signaling. RNF220 promoted STAT1 ubiquitination and phosphorylation through a positive feedback loop. RNF220 haploinsufficiency impaired IFN signaling, and RNF220-defective mice were more susceptible to A. baumannii and HSV-1 infection than WT mice. Our work offers novel insights into the mechanisms of STAT1 modulation and provides potential therapeutic targets against bacterial and viral infection and inflammatory diseases.


β-Glycerol phosphate/genipin chitosan hydrogels: A comparative study of their properties and diclofenac delivery.
Thermosensitive hydrogels based on polysaccharides are suitable candidates for the design of biodegradable and biocompatible injectable drug delivery systems. Thus, the combination of chitosan (CHI) and β-glycerol phosphate disodium salt (β-GP) has been intensively investigated to develop thermo-induced physical gels. With the aim of exploring the possibilities of optimization of these hydrogels, in this work, chitosan, β-GP and naturally extracted crosslinking agent, genipin (GEN), have been successfully combined, obtaining co-crosslinked hydrogels with both in situ physical and covalent crosslinking. A wide range of β-GP concentrations have been selected in order to analyze its influence on a variety of properties, including gelation time, pore size, water uptake ability, in vitro hydrolytic and enzymatic degradation, mucoadhesion and mechanical and rheological properties. Furthermore, the potential application of the developed systems for the administration and controlled release of an anti-inflammatory anionic drug, such as diclofenac, has been successfully demonstrated.


Inhibition of juvenile hormone biosynthesis in mosquitoes: effect of allatostatic head factors, PISCF- and YXFGL-amide-allatostatins.
We investigated the role of head factors and allatostatins (ASs) on the regulation of juvenile hormone (JH) synthesis in female adult mosquito. The biosynthetic activity of the Aedes aegypti corpora allata (CA) in vitro was inhibited by factors present in the head. Disconnecting the CA from the brain resulted in a significant increase in the rate of JH biosynthesis. Inhibition was not dependent on intact nervous connections; co-incubation of CA with brains or brain extracts resulted in a significant decrease of JH biosynthesis. This inhibitory effect of brain extracts was reversible and heat stable; extracts lost the inhibitory activity after proteinase K digestion suggesting a peptidic structure. In a first attempt to elucidate the nature of this inhibitory factor, we tested in our CA in vitro system the effect of members of two families of allatostatins already described in mosquitoes. Anopheles gambiae PISCF-allatostatin (homolog to Manduca PISCF-allatostatin) significantly inhibited JH synthesis, while Ae. aegypti YXFGL-amide-allatostatins (homologs to cockroach YXFGL-amide-allatostatins) did not affect JH synthesis. These results represent the first description of an allatostatic effect of PISCF-allatostatins outside the Lepidoptera.


Biomechanical and clinical evaluation of the expandable intramedullary fixation device.
The use of an expandable intramedullary device for internal fixation of metacarpal or phalangeal bones is described. The device is applicable to transverse fractures, short oblique fractures, or transverse osteotomies. The device consists of a cylindrical apparatus made of titanium that allows collapse in the circumferential diameter. It is introduced into the medullary canal in its collapsed state, and on release expands to its normal diameter in the canal with the fracture reduced over it. A biomechanical evaluation compared the stability of this device with other commonly employed fixation methods. A retrospective review is presented of the first 43 patients in whom the device was implanted.


Biodistribution of 64Cu in inflamed rats following administration of two anti-inflammatory copper complexes.
64Cu was administered in two anti-inflammatory formulations to normal rats and to rats with 2 forms of local inflammation, namely (a) an acute paw oedema (elicited with carrageenan) or (b) a chronic granulomatous response to an implanted irritant (Mycobacterium tuberculosis in a polyurethane sponge). The copper formulations used were (i) a slow release one consisting of Cu(II) salicylate applied dermally with ethanol/DMSO and (ii) short acting hydrophilic complex (Cu(I)Cu(II)-penicillamine)5- given subcutaneously. Three types of changes in copper biodistribution with these forms of inflammation were discerned based on determination of 64Cu and copper content in the following organs: inflammatory locus (foot or sponge implant), kidney, liver, spleen, adrenals, brain, blood, thymus, heart, and skin (site of application). The most evident changes were in the kidneys, liver, spleen, adrenals, thymus and serum from animals with chronic granulomatous inflammation. In contrast, a short term acute inflammatory stress (carrageenan paw oedema) had little effect. While copper D-penicillamine (applied subcutaneously) appeared to move as a bolus through the animals, the results with the percutaneous copper salicylate formulation are consistent with it providing a slow release source of copper(II). Exogenous 64Cu from both formulations was sequestered at inflammatory sites (relative to serum). This may partly explain how applied copper complexes can be anti-inflammatory.


Infantile neurodevelopmental outcome after fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome: the first prospective experience from Iran.
We sought to evaluate the neurodevelopmental outcomes at 12 months of age among infants with twin-to-twin transfusion syndrome (TTTS) undergoing fetoscopic laser photocoagulation (FLP). In this prospective longitudinal study, neurodevelopmental assessment was performed among the infants at the corrected age of 12 months, who were diagnosed with TTTS and treated by FLP. The Ages and Stages Questionnaire (ASQ) was filled out by parents. In the next step in infants with abnormal ASQ, motor and cognitive developments were evaluated by Bayley's infant and toddler development scoring system (Bayley 3-Third edition). In 39 FLP procedures the rate of live birth of at least one twin was 73.8%. Four neonatal deaths were recorded, three of which were due to prematurity and one was due to heart anomaly. The ASQ was normal in 89.7% (35/39) of the infants (group I), 5.1% (2/39) had minor neurodevelopmental impairment (NDI) (group II), and 5.1% (2/39) had major NDI (group III). The 4 infants with abnormal ASQ had Bayley examination which showed two with mild to moderate cerebral palsy and two had delayed verbal skills and autistic spectrum disorder. No significant difference was noted between survivors with and without NDI with respect to donor or recipient status, birth weight, gestational age at birth, Quintero stage of TTTS. In addition, the relationship between gestational age at the time of undergoing FLC and NDI was not significant. In our population, minor and major neurodevelopmental impairment were seen in 10.2% of the infants. This information is useful for counseling our couples in this population prior the procedure.


The first analogues of LNA (locked nucleic acids): phosphorothioate-LNA and 2'-thio-LNA.
LNA (Locked Nucleic Acids, 1, X = O, Y = O) is a novel oligonucleotide analogue capable of recognizing complementary DNA and RNA with unprecedented thermal affinities. Synthesis of the first chemically modified LNA analogues is reported. A 9-mer phosphorothioate-LNA containing three LNA thymine monomers (1, X = O, Y = S, Base = thymin-1-yl) and 9-mer LNAs containing one, three or five 2'-thio-LNA monomers (1, X = S, Y = O, Base = uracil-1-yl) were able to recognize both complementary DNA and RNA with thermal affinities comparable to those of parent LNA.


Cost reduction in abdominal CT by weight-adjusted dose.
To analyze the influence of contrast dose adjusted by weight vs. fixed contrast dose in the attenuation and cost of abdominal computed tomography (CT). A randomised, consecutive, parallel group study was conducted in 151 patients (74 men and 77 women, age range 22-67 years), studied with the same CT helical protocol. A dose at 1.75 ml/kg was administered in 101 patients while 50 patients had a fixed dose of 120 ml of same non-ionic contrast material (320 mg/ml). Mean enhancements were measured at right hepatic lobe, superior abdominal aorta and inferior cava vein. Statistical analysis was weight-stratified (<60, 61-70, 71-80 and >81 kg). Aortic attenuation was significantly superior (p<0.05) in the dose adjusted by weight group than in the fixed dose group. Patients who weighed >61 kg in dose-adjusted group, presented higher hepatic attenuation, being statistically significant in those >81 kg (p<0.01). In dose-adjusted group, there was a savings of euro 4.1 per patient in patients weighing <80 kg. In patients weighing >80 kg, there was an over cost of euro 10.7 per patient. An injection volume of 1.75 ml/kg offers an optimal diagnostic quality with a global savings of euro 1.34 per patient.


Measuring system of care core values in a behavioral health system of care.
The Comprehensive Services for Children and Their Families or System of Care (SOC) is the largest mental health project ever conducted by the US federal government. These programs are based on a value-driven framework that includes: child/youth centered and family driven practice, community-based practice, and culturally competent practice (Stroul and Friedman in A system of care for children and youth with severe emotional disturbances, Georgetown University Child Development Center, CASSP Technical Assistance Center, Washington, DC, 1986). The aim of this study is to determine the extent of the adoption of SOC values by families, system partners, providers and community organizations in a countywide SOC. Using a retrospective design, data was collected through a system-wide survey and focus groups, which asked respondents to rate the presence of SOC core values prior to and four years following its creation. Results suggest that system partners, provider staff, and families are aware of the changes that have occurred within the system as a result of the SOC.


Asymptomatic patent ductus arteriosus in a 41-year-old woman.
Patent ductus arteriosus is a rare adult congenital heart disease, especially asymptomatic cases are uncommon in older ages. We report here the case of a 41-year-old woman, who was incidentally found to have a patent ductus arteriosus. The patient also was asymptomatic. For anatomical demonstration, computerized tomography angiography was performed and then surgical intervention was applied.


Denervation and senescence markers data from old rats with intrinsic differences in responsiveness to aerobic training.
The data described below is related to the manuscript "Late life maintenance and enhancement of functional exercise capacity in low and high responding rats after low intensity treadmill training" [1]. Rodents exhibit age-related declines in skeletal muscle function that is associated with muscle denervation and cellular senescence. Exercise training is a proven method to delay or even reverse some aging phenotypes, thus improving healthspan in the elderly. The beneficial effects of exercise to preserve muscle may be reliant on an individual's innate ability to adapt to aerobic training. To examine this question, we assessed aged rats that were selectively bred to be either minimally or highly responsive to aerobic exercise training. We specifically asked whether mild treadmill training initiated late in life would be beneficial to preserve muscle function in high response and low response trainer rats. We examined gene expression data on markers of denervation and senescence. We also evaluated measures of aerobic training and neuromuscular muscle function through work capacity, contractile properties, and endplate fragmentation for further analysis of the aging phenotype in older rodents.


Identification of toxicants from marine sediment using effect-directed analysis.
Effect-directed analysis (EDA) has been reported to be a powerful tool for the identification of the responsible toxicants in contaminated, hazardous environmental samples. The aim of this study was to investigate whether it also is possible to use currently available EDA methodology to identify potentially relevant toxicants in samples that do not pose obvious problems. For this purpose, compounds extracted from a marine sediment sample from the west coast of Sweden were separated into distinct fractions, using two preparative chromatographic techniques. One algal bioassay using Scenedesmus vacuolatus and two bacterial bioassays using Vibrio fischeri were applied as detectors of toxicity, representing acute and chronic end points. Chronic algal toxicity was a powerful tool for discriminating between toxic and nontoxic fractions, whereas acute and chronic bacterial toxicity failed to identify toxic fractions. Eight compounds were identified as potentially relevant toxicants by chemical analysis of toxic fractions: anthracene, fluoranthene, pyrene, benzo[a]anthracene, benzo[b]fluoranthene, benzo[a]pyrene, benzo[k]fluoranthene, and indeno[1,2,3-cd]pyrene.


Microcirculatory haemodynamics before and after vascular surgery in severe limb ischaemia--the relation to post-operative oedema formation.
To determine whether postoperative oedema could be predicted preoperatively by microcirculatory parameters, we studied nutritive capillary blood flow in 21 patients before and after limb salvage procedures. All patients had severe lower limb ischaemia and underwent femoro-popliteal or femoro-crural bypass surgery. The systolic ankle-branchial arm index and systolic toe pressure were used as macrocirculatory parameters. Intravital capillary microscopy was used to measure red blood cell (RBC) and peak RBC velocity and time to peak RBC velocity after release of a 1 min arterial occlusion in the nailfold of the toe. Transcutaneous pO2 was measured on the dorsum of the foot at rest, during oxygen inhalation and following a release of a 5 min occlusion. After surgery the mean systolic ankle-brachial index and systolic toe pressure and all transcutaneous pO2 parameters improved significantly (P less than 0.001). Mean peak RBC velocity increased from 0.156 mm/s to 0.310 mm/s (P less than 0.05), indicating that the reactive hyperaemic response in the capillary bed had improved. Eleven patients developed postoperative oedema. There were no differences in postoperative macro and microcirculatory parameters between the patients with oedema (n = 11) and those without oedema (n = 10). However, preoperatively RBC velocity and peak RBC velocity were significantly lower (P less than 0.05) and time to peak RBC velocity was significantly longer (P less than 0.01) in patients who developed oedema. These findings show that in patients with severe limb ischaemia vascular surgery improves both macro- and microcirculatory blood flow, but that these patients develop oedema after vascular surgery when microcirculatory blood flow is compromised preoperatively.


Screening for trisomy 21 by fetal nuchal translucency and maternal age: a multicenter project in Germany, Austria and Switzerland.
To examine the effectiveness of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation in Germany, Austria and Switzerland. This was a multicenter study of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. All the sonographers involved in the study had received The Fetal Medicine Foundation Certificate of Competence in the 10-14-week scan. Fetal nuchal translucency thickness and crown-rump length were measured in 23 805 singleton pregnancies with live fetuses. In each case the risk for trisomy 21 was estimated on the basis of maternal age and fetal nuchal translucency thickness for crown-rump length with the use of The Fetal Medicine Foundation's software. The distribution of estimated risk was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 was calculated. Fetal nuchal translucency thickness was successfully measured in all 23 805 pregnancies and outcome was available in 21 959. The median maternal age was 33 (range 15-49) years and in 7935 (36.1%) the age was 35 years or greater. The median gestation at screening was 12 (10-14) weeks and the median fetal crown-rump length was 61 (range 38-84) mm. The estimated risk for trisomy 21 based on maternal age and fetal nuchal translucency thickness for crown-rump length was 1 in 300 or greater in 13.0% (2800 of 21 475) normal pregnancies, in 87.6% (184 of 210) of those with trisomy 21 and in 87.2% (239 of 274) with other chromosomal defects. In Germany, Austria and Switzerland the results of screening for chromosomal defects by measurement of fetal nuchal translucency thickness, in centers with appropriately qualified sonographers and using The Fetal Medicine Foundation's software, are similar to those reported in the UK using the same methodology.


Paravalvular Leaks-From Diagnosis to Management.
As the number of surgical and transcatheter valve replacements continue to increase in the aging population, so does the incidence of paravalvular leak (PVL). Given its impact on morbidity and mortality, this article will focus on the epidemiology, clinical presentation, diagnostic assessment, and available treatments for PVL. Despite being performed on inoperable and typically higher risk patients, short-term complication rates of transcatheter PVL closure appear relatively low (< 10%). When indirectly compared with surgical PVL closure, long-term mortality, reoperation rates and degree of symptom improvement are similar. Nonetheless, current transcatheter closure devices are off-label and repurposed from other indications. Further development of percutaneous closure devices is an essential next step in order to improve and optimize outcomes. In patients with surgical and especially transcatheter-replaced heart valves, clinicians need to maintain vigilance for the presence of PVL, particularly in those with new-onset heart failure or hemolysis. Multimodality imaging is essential to detect and quantify PVL. Echocardiography (both transthoracic and transesophageal) is the backbone of diagnosis and quantification, and cardiac computed tomography and cardiac magnetic resonance imaging play an important role in defect characterization and in periprocedural planning. For those patients who are unable to undergo surgery, transcatheter PVL closure is an appropriate next step in management as it has similar outcomes to surgical intervention when performed in a center of expertise.


Examination of the importance of age of onset, callous-unemotional traits and anger dysregulation in youths with antisocial behaviors.
Age of onset, callous-unemotional (CU) traits and anger dysregulation have separately been proposed as relevant factors in explaining the heterogeneity of antisocial behaviour (ASB). Taking a dimensional perspective, this study examined the specific contributions and the mutual influences (i.e., interactions) of these three characteristics on specific dimensions of ASB (i.e., criminal behaviours and externalizing symptoms). Assessments were conducted on 536 youths from institutions with the youth psychopathic traits inventory (CU traits), the Massachusetts youth screening instrument-second version (anger dysregulation), the criminology questionnaire (criminal behaviours) and the child behavior checklist (externalizing symptoms), rated by both the youths and their carers. Using Bayes as estimators, the results revealed that the number and frequency of crimes (and, more specifically, damage to property, property offenses and media crimes) were explained by a specific contribution of each factor (age of onset, CU traits and anger dysregulation). Additionally, the interactions between age of onset and CU traits or anger dysregulation were relevant predictors of some types of crimes (i.e., damage to property, property offences and media crimes). Furthermore, when rated by youths, externalizing symptoms were explained by CU traits and anger dysregulation. However, when rated by the carer, anger dysregulation was more important in explaining externalizing symptoms. This study highlights the importance of considering these factors altogether and the value of using a dimensional perspective when examining the structure of ASB in youths. Consequently, future classifications should take into account the mutual account of these characteristics, which were previously studied separately.


The optimal anticoagulant therapy for mechanical heart valves in a gallbladder cancer patient with hepatic metastases: A case report.
Developing an optimal anticoagulant strategy poses a challenging task in patients with mechanical heart valves (MHVs) throughout their lifetime. We report an optimal anticoagulant therapy in a cancer patient with hepatic metastases after MHV replacement. A 68-year-old female with MHVs suffered from gallbladder cancer with hepatic metastases. Her international normalized ratio (INR) fluctuated owing to the declined hepatic function. Gallbladder cancer and hepatic metastases, with a history of mechanic aortic valve replacement and mitral valve replacement. Warfarin was discontinued and Vitamin K1 was immediately administrated via intravenous infusion. low-molecular-weight heparin (LMWH) was regarded as a preferable option, and nadroparin at the dosage of 4100IU daily was administered. No adverse event occurred during the patient's hospitalization and two-week follow up after discharge. LMWH may represent a reasonable alternative regarding the inhibition of thrombus and bleeding in MHVs carriers with cancer and hepatic metastases.


The role of calcium ions and bile salts on the pancreatic lipase-catalyzed hydrolysis of triglyceride emulsions stabilized with lecithin.
Lecithin-stabilized triglyceride emulsions are subject to hydrolysis by pancreatic lipase. The time profiles of these reactions are characterized by a lag-phase and a zero-order phase. Lag phases are more pronounced with long-chain triglycerides. Ca2+ is effective in reducing the lag-phase and activating lipase. Kinetic analysis of the reactions suggests that, like previous findings by others, taurodeoxycholate (TDC) micellar solutions combine with the lipase-colipase complex to form another catalytically active enzyme form. This enzyme form exhibits reduced activity in the absence of Ca2+. In the presence of Ca2+ the mixed micelle-lipase complex becomes more active and opens a new pathway for lipolysis. It is suggested that this enzyme form can bind more easily to interfaces with different physicochemical properties. Under these conditions, Ca2+ activates the lipolysis of short-, medium-, and long-chain triglycerides by a similar mechanism. Maximum activities were measured in the presence of approximately 6 mM TDC and 30 mM Ca2+. The experimental conditions approximate the physiological conditions in the gastrointestinal tract since all of the factors studied here have been reported to be necessary for in vivo lipolysis and/or absorption of triglycerides. A mechanistic model for lipolysis in the presence of Ca2+ and the bile salt TDC is proposed which accounts for most of the experimental observations in a quantitative manner.


[Osteosynthesis with hinge joints and methylmethacrylate (author's transl)].
Six cases have been described where an osteosynthesis was performed using the stem of a hinge knee joint in combination with methylmethacrylate and other osteosynthetic devices (screws, wires). Need for an osteosynthesis existed because of pseudarthrosis after supracondylar and high tibial osteotomies, intraoperative fracture for implantation of a total knee, reimplantation after deep infection, and fatigue fracture after a total knee. The advantage of the procedure lies in early mobilisation and weight bearing. We do not believe in reimplantation after an infected prosthesis. Instead, we recommend fusion after implant removal.


Generation of Efficient Germ-Line Chimeras Using Embryonic Stem Cell Injection.
There are many different reasons for producing germ-line chimeras, so a method for producing these is very important both for the testing of stem cells (SC) and for the production of an animal which may be genetically modified (Voncken, Methods Mol Biol 693:11-36, 2011). As with many scientific procedures the theory behind the process is very simple: in this case injection of cells into the blastocoel cavity of an embryo which has developed to the blastocyst stage so as the injected cells can contribute to the inner cell mass (ICM) and hopefully contribute to the germ line of the animal produced (Schneider et al., Stem Cell Rev 5(4):369-377, 2009). Incorporation of the cells into the gonads of the animal produced will allow the testing of those cells and the resulting animal which may be derived from the injected cells (Bradley et al., Nature 309(5965):255-256, 1984). The problems arise because of the size of the cells and the challenge of injection into the blastocoel cavity of a developing embryo.


[Stimulation specific visual evoked responses (V.E.R.) in clinical use (author's transl)].
Out of the many different kind of stimuli used to elicit V.E.R., two classes are of practical clinical use. Luminance V.E.R. give information on the macular area and can be used through opaque media and in infants. Pattern stimulation may give information on visual acuity (foveolar function) or on conduction disturbances in the optic nerve. Pattern stimulation can be used in children under 1 year of age.


Student voice - Care begins at home.
WHILE I don't imagine anyone in any line of work feels happy about calling in sick, I have never known anyone experience the same level of guilt about it as nurses.


Mechanical and antibacterial properties of the chitosan coated cellulose paper for packaging applications: Effects of molecular weight types and concentrations of chitosan.
Chitosan with low (25 kDa) and high molecular weight (2100 kDa) were used to enhance performances of paper made from steam-exploded bamboo fibers and nanofibrillated cellulose. Chitosan solutions with concentrations of 0-1.0 wt% were manually applied on paper surface using a facile coating approach with a wire bar. Effects of chitosan coatings on morphology, thermal stability, wettability, mechanical performances and antibacterial properties of the paper were investigated. The larger improvement in the mechanical properties and wettability of the chitosan coated paper was observed with increasing concentrations of chitosan due to the disappearance of empty pores between fibers within a cellulose network by the formed chitosan matrix. These improvements were significantly higher when high molecular weight chitosan was applied. Yet, the addition of chitosan slightly decreased the thermal stability of the coated paper, and the chitosan coating did not improve the antimicrobial properties of the paper. The antimicrobial activity of chitosan against Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) was found to be diminished when a chitosan solution was entrapped within paper. Together with the overall migration of the paper in food simulants, the results suggested that the chitosan coated paper could be applied for non-food-direct-contact packaging materials.


First report of closantel treatment failure against Fasciola hepatica in cattle.
Control of Fasciola hepatica infection in livestock is based on annual treatment using flukicides such as triclabendazole, albendazole and closantel. However, triclabendazole resistant F. hepatica populations are emerging worldwide and resistance is emerging to albendazole, whereas it has until now never been described for closantel. In Sweden, a topical formulation containing a combination of closantel and ivermectin (Closamectin Pour On) has been registered for use in cattle only since 2011. This study evaluated the efficacy of closantel against F. hepatica in naturally infected beef cattle using both coproantigen and faecal egg count reduction tests. Faecal egg counts (FEC) and coproantigen ELISA examinations were conducted in February 2014 in three beef cattle herds (A, B, C) in south-western Sweden. On each farm, 10 F. hepatica coproantigen-positive and F. hepatica egg-positive animals were allocated after 12-16 weeks of housing into groups and treated topically with a minimum of 20 mg closantel per kg body weight. Faecal samples were collected from selected animals on 0, 7 and 21 day post-treatment (PT). Based on FEC, closantel efficacy 21 days PT was 72% (95% CI: 65-77%) and 97% (95% CI: 95-98%) on farms A and B, respectively. No FEC reduction at all was observed on farm C. In total, 4, 1 and 6 animals remained coproantigen-positive at 21 days PT on farms A, B and C, respectively. Closantel treatment failure was confirmed on two of the farms. As the animals were housed 12-16 weeks before treatment and thereafter during the entire study, failure due to the presence of juvenile flukes was excluded. Although the cause of closantel failure currently remains unclear, development of resistance or/and absorption failure of topical administration should be considered. To our knowledge, this is the first report of closantel treatment failure against F. hepatica in cattle.


Coronavirus Disease (COVID-19) Pandemic: The Psychological Well-Being in a Cohort of Workers of a Multinational Company.
The aim of the present study was to evaluate the psychological well-being (PWB) during the coronavirus disease (COVID-19) pandemic in workers of a multinational company. Employees (aged ≥18 years) were recruited from Latin American, North American, New Zealand, and European sites of a multinational company operative during all the pandemic period. The self-reported Psychological General Well-Being Index was used to assess the global PWB and the effects on six subdomains: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. The influencing role of age, gender, geographical location, COVID-19 epidemiology, and restrictive measures adopted to control the pandemic was explored. A total of 1335 workers completed the survey. The aggregate median PWB global score was in a positive range, with significantly better outcomes detected in the Mexican and Colombian Latin American sites compared with the other worldwide countries (p < 0.001). Among the European locations, a significantly higher PWB score was determined in Spain compared with the German and French sites (p < 0.05). Comparable geographical trends were demonstrated for all the PWB subdomains. Male workers had a significantly better PWB compared with females (p < 0.05), whereas a negative correlation emerged with aging (p = 0.01). COVID-19 epidemiology and pandemic control measures had no clear effects on PWB. Monitoring PWB and the impact of individual and pandemic-related variables may be helpful to clarify the mental health effects of pandemic, define targeted psychological-supporting measures, also in the workplace, to face such a complex situation in a more constructive way.


Validity of Italian administrative healthcare data in describing the real-world utilization of infusive antineoplastic drugs: the study case of rituximab use in patients treated at the University Hospital of Siena for onco-haematological indications.
Italian administrative healthcare databases are frequently used for studies on real-world drug utilization. However, there is currently a lack of evidence on the accuracy of administrative data in describing the use of infusive antineoplastics. In this study, we used rituximab as a case study to investigate the validity of the regional administrative healthcare database of Tuscany (RAD) in describing the utilization of infusive antineoplastics. We identified patients aged 18 years or older who had received ≥1 rituximab administration between 2011 and 2014 in the onco-haematology ward of the University Hospital of Siena. We retrieved this information from the Hospital Pharmacy Database (HPD-UHS) and linked the person-level information to RAD. Patients who had received ≥1dispensing of rituximab, single administration episodes, and patients treated for non-Hodgkin Lymphoma (nHL) or Chronic Lymphocytic Leukemia (CLL) were identified in RAD and validated using HPD-UHS as the reference standard. We identified the indications of use using algorithms based on diagnostic codes (ICD9CM codes, nHL=200*, 202*; CLL=204.1). We tested 22 algorithms of different complexity for each indication of use and calculated sensitivity and positive predictive value (PPV), with 95% confidence intervals (95%CI), as measures of validity. According to HPD-UHS, 307 patients received rituximab for nHL (N=174), CLL (N=21), or other unspecified indications (N=112) in the onco-haematology ward of the University Hospital of Siena. We identified 295 rituximab users in RAD (sensitivity=96.1%), but PPV could not be assessed due to missing information in RAD on dispensing hospital wards. We identified individual rituximab administration episodes with sensitivity=78.6% [95%CI: 76.4-80.6] and PPV=87.6% [95%CI: 86.1-89.2]. Sensitivity of algorithms tested for identifying nHL and CLL ranged from 87.7% to 91.9% for nHL and from 52.4% to 82.7% for CLL. PPV ranged from 64.7% to 66.1% for nHL and from 32.4% to 37.5% for CLL. Our findings suggest that RAD is a very sensitive source of information for identifying patients who received rituximab for onco-haematological indications. Single administration episodes were identified with good-to-high accuracy. Patients receiving rituximab for nHL were identified with high sensitivity and acceptable PPV, while the validity for CLL was suboptimal.


Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells.
The p16 tumor suppressor gene is frequently inactivated in human cancer tissues and cell lines. We previously reported that wild-type p16 expression from an adenovirus vector (Adv/p16) induced p53-dependent apoptotic cell death in non-small cell lung cancer (NSCLC) cell lines. Here we show the potential mechanism of apoptosis induced by Adv/p16 infection. Infection of human NSCLC cell line A549, which carries the wild-type p53 gene, with Adv/p16 resulted in activation of caspase-3, accompanied by the cleavage of its substrate poly (ADP-ribose) polymerase (PARP), on day 3 of infection. The retinoblastoma (Rb) cell cycle regulator protein was also cleaved after activation of caspase-3; when the levels of Rb significantly diminished, apoptosis began. When A549 cells were pretreated with the caspase-inhibitory peptide N-acetyl-asp-Glu-Val-Asp-CHO (aldehyde) (Ac-DEVD-CHO), Adv/p16-mediated apoptosis and Rb cleavage were greatly inhibited. Furthermore, MDM2, a negative regulator of p53 expression was upregulated 3 days after Adv/p16 infection, and MDM2 was subsequently cleaved by caspase-3; MDM2 cleavage was inhibited by Ac-DEVD-CHO treatment. These data implied that cleavage of Rb, in addition to activation of caspase-3, represented a mechanism by which Adv/p16 induced apoptotic cell death in human NSCLC cells. Our results support the clinical relevance of Adv/p16 as a treatment for p16-null human NSCLC that express wild-type p53.


Involvement of Fas/Fas ligand system-mediated apoptosis in the development of concanavalin A-induced hepatitis.
Concanavalin A (Con A)-induced hepatitis is an experimental hepatitis model in which hepatic injury is caused by the action of cytokines produced by T cells. Using IFN-gamma-deficient mice, we previously demonstrated that IFN-gamma plays a central role in Con A-induced hepatitis. Here, we show that development of the disease is completely suppressed in gld/gld mice, in which Fas ligand is defective. In contrast, suppression of the disease in Ipr/Ipr mice was incomplete, since a small amount of the fas mRNA was produced in these mice. The data indicate that activation of the Fas/Fas ligand system is a necessary step in the development of Con A-induced hepatitis. Furthermore, we found that not only fas but also caspase-1 expression was reduced in IFN-gamma-deficient mice. Since caspase-1 is an integral component of Fas signal transduction, these observations suggest that IFN-gamma-induced activation of both fas and caspase-1 expression causes enhancement of hepatocyte apoptosis resulting in the development of hepatitis.


Assembly of the type III secretion needle complex of Salmonella typhimurium.
The type III secretion needle complex (NC) of Salmonella typhimurium is a complex secretory system that functions to translocate virulence proteins into eukaryotic cells. Evolutionarily it is related to bacterial flagella. Assembly of the NC occurs through ordered secretion, polymerization, and assembly, and requires the coordinated expression and association of over 20 different proteins. Recent progress in the understanding of the assembly and architecture of the NC is reviewed.


Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.
The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial.


Defending the city's cleanliness with their lives? A study of road traffic collisions involving sanitation workers in China over five years.
With increasing urbanization in developing countries, sanitation workers are frequently involved in road traffic collisions. Our purpose was to study specific collisions involving sanitation workers and provide decision-making suggestions and reference measures for the sanitation industry and urban managers to reduce the occurrence of collisions. We obtained online news data about sanitation worker road traffic collisions in China between 2013 and 2017 and analyzed occurrence time and location, victim characteristics, and causes of collisions. In China, between 2013 and 2017, 511 road traffic collisions were reported, with the fewest in February and July. Most occurred around 5:00 a.m. in Eastern regions and in urban areas. Victims were mainly over 50 years old, with more females than males. Collisions usually resulted in death at the scene. The ambiguity of laws, the exploitation of workers through industry outsourcing, and the difficulty of processing claims may be the main factors preventing victims from obtaining legal compensation. The most common cause of collisions was drivers' speeding, but workers also regularly risk death by crossing the road in pursuit of their duties. The absence of legal controls for environmental protection, the excessive pursuit of efficiency in urban governance, and the lack of basic education of sanitation workers are underlying causes of collisions. Raising awareness about sanitation worker road traffic collisions will help protect the work safety rights of this vulnerable group.


Stress-related salivary alpha-amylase (sAA) activity in alcohol dependent patients with and without a history of childhood maltreatment.
Alcohol-dependent (AD) patients with a history of childhood maltreatment (CM) have shown a more severe clinical profile and a higher risk of relapse than those without CM. It was hypothesized that stress responsivity plays an important role in moderating the relationship between CM and AD. Surprisingly, systematic investigations about the stress responsivity in AD patients with CM are rare. This study compared physiological and subjective stress responses in AD patients with and without CM as well as in healthy controls with and without CM. A total of 130 participants performed the Trier Social Stress Test (TSST). Physiological stress reactivity related to the noradrenergic system was assessed by salivary alpha-amylase (sAA) activity. Subjective ratings of anxiety, nervousness, distress, and mood were rated on visual analogue scales. AD patients showed significantly lower stress-related sAA activity than healthy controls (p ≤ 0.024; z ≥ 1.97). A different pattern was found in the subjective ratings. In particular, anticipatory anxiety revealed a clear effect of CM (p ≤ 0.005; z ≥ 2.43) but no difference between AD patients and healthy controls (p > 0.05). After the TSST, distress ratings differed between AD patients with CM and AD patients without CM (p ≤ 0.009; z ≥ 2.61). The discrepancy between physiological responsivity and subjective stress experiences may account for an increased inability to cope with stressful situations, which in turn might explain the enhanced risk of relapse in AD patients with a history of CM during early abstinence.


Cost-effectiveness of an exercise and nutritional intervention versus usual nutritional care during adjuvant treatment for localized breast cancer: the PASAPAS randomized controlled trial.
We undertook a cost-effectiveness analysis (CEA) to compare an exercise and nutritional program with the usual nutritional care concomitant to adjuvant chemotherapy in localized breast cancer patients. The CEA was designed as part of the interventional, controlled, randomized, single-center, open-label PASAPAS study. Breast cancer patients receiving first-line adjuvant chemotherapy at a French Comprehensive Cancer Center were randomized 2:1 to a 6-month exercise program of supervised indoor and outdoor group sessions in addition to usual nutritional care (exercise arm) or a usual nutritional care group receiving dietary and physical activity counseling (control arm). Costs were assessed from the French national insurance perspective (in Euros, 2012). Incremental cost-effectiveness ratios (ICERs) were calculated for four criteria: body mass index, waist circumference, body fat percentage, and estimated aerobic capacity. Uncertainty around the ICERs was captured by a probabilistic analysis using a non-parametric bootstrap method. The analysis was based on 60 patients enrolled between 2011 and 2013. Average intervention costs per participant were €412 in the exercise arm (n = 41) and €117 (n = 19) in the control arm. Total mean costs were €17,344 (standard deviation 9,928) and €20,615 (standard deviation 14,904), respectively, did not differ significantly (p = 0.51). The 6-month exercise program was deemed to be cost-effective compared with usual care for the estimated aerobic capacity. Multicenter randomized studies with long-term costs and outcomes should be done to provide additional evidence. Clinical trial: The PASAPAS study is registered under ClinicalTrials.gov. Trial registration ID: NCT01331772.


Effect of linear running velocity on the increase on foot pronation.
The purpose of this study was to investigate the behavior of foot pronation at different percentages of peak velocity in 23 physically active men. An ergospirometric test was carried out with an initial velocity of 9kmh-1 and increments of 1kmh-1 until exhaustion. 2D kinematic analysis was performed in the posterior frontal plane at all velocities to identify the maximal angle of pronation (MAP) of the right leg. The analyses were performed between the initial periods (0%), 25%, 50%, 75%, and 100% (peak of velocity - PV). All comparisons of the PV phases with the MAP showed an increase in the angle of foot pronation, with the exception of between the start and 25% of PV. Only 4 (∼17%) subjects maintained MAP values within a normal range until PV was reached. Control of the volume and intensity of training, as well as the running technique is suggested and strengthening of the muscles responsible for stabilization of the foot pronation.


Purification and properties of phosphorylase from Phymatotrichum omnivorum.
The glycogen phosphorylase (EC 18.104.22.168) from the mycelium of Phymatotrichum omnivorum was purified by ammonium sulfate fractionation, gel filtration on Sephacryl S-200, and DEAE-cellulose ion-exchange chromatography to more than 100-fold. The purified enzyme was homogeneous; this was confirmed by polyacrylamide gel electrophoresis. Sodium dodecyl sulfate-gel electrophoresis indicated the relative molecular size of the enzyme was around 145,000. The approximate molecular weight by gel filtration was 116,000. The optimum pH of the enzyme was 7.0 and the enzyme was more specific for glycogen, with a Km value of 0.36 mg/ml. Nucleotides AMP, ADP, and ATP and compounds containing an "SH" group inhibited the enzyme activity. Diethyldithiocarbamate, EDTA, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, and Cu2+ were the potent inhibitors of the glycogen phosphorylase activity, Ca2+, Cu2+, Co2+, and Fe2+ stimulated the enzyme activity. The enzyme preparation was stable at 4 degrees C during a period of 30 days.


The postural control can be optimized by the first movement initiation condition encountered when submitted to muscle fatigue.
We investigated whether and how the movement initiation condition (IC) encountered during the early movements performed following focal muscle fatigue affects the postural control of discrete ballistic movements. For this purpose, subjects performed shoulder flexions in a standing posture at maximal velocity under two movement IC, i.e., in self-paced conditions and submitted to a Stroop-like task in which participants had to trigger fast shoulder flexions at the presentation of incongruent colors. Shoulder flexion kinematics, surface muscle activity of focal and postural muscles as well as center-of-pressure kinematics were recorded. The initial IC and the order in which subjects were submitted to these two conditions were varied within two separate experimental sessions. IC schedule was repeated before and after fatigue protocols involving shoulder flexors. The aim of this fatigue procedure was to affect acceleration-generating capacities of focal muscles. In such conditions, the postural muscle activity preceding and accompanying movement execution is expected to decrease. Following fatigue, when subjects initially moved in self-paced conditions, postural muscle activity decreased and scaled to the lower focal peak acceleration. This postural strategy then transferred to the Stroop-like task. In contrast, when subjects initially moved submitted to the Stroop-like task, postural muscle activity did not decrease and this transferred to self-paced movements. Regarding the center-of-pressure peak velocity, which is indicative of the efficiency of the postural actions generated in stabilizing posture, no difference appeared between the two sessions post-fatigue. This highlights an optimization of the postural actions when subjects first moved in self-paced conditions, smaller postural muscle activation levels resulting in similar postural consequences. In conclusion, the level of neuromuscular activity associated with the postural control is affected and can be optimized by the initial movement IC experienced post-fatigue. Beyond the fundamental contributions arising from these results, we point out potential applications for trainers and sports instructors.


In-vitro activity of the combinations of ampicillin with mecillinam or with beta-lactamase inhibitors against strains resistant to ampicillin.
The in-vitro activity of ampicillin, of mecillinam and of combinations of ampicillin with mecillinam, clavulanic acid or 6 beta-bromopenicillanic acid has been studied against 126 Enterobacteriaceae resistant to ampicillin. The combination of ampicillin with mecillinam showed synergy or addition in 60% of the combinations tested. Synergy was seen especially when the strains were resistant to mecillinam, indifference when they were susceptible to mecillinam. The combination of ampicillin with mecillinam was more active than the combination with clavulanic acid against Escherichia coli, Klebsiella and Enterobacter, but not against Proteus, Morganella and Providencia. The combination of ampicillin with clavulanic acid was more active than the combination with 6 beta-bromopenicillanic acid in E. coli, Klebsiella and Enterobacter strains.


Therapeutic effects of stem cells and substrate reduction in juvenile Sandhoff mice.
Sandhoff Disease (SD) involves the CNS accumulation of ganglioside GM2 and asialo-GM2 (GA2) due to inherited defects in the β-subunit gene of β-hexosaminidase A and B (Hexb gene). Substrate reduction therapy, utilizing imino sugar N-butyldeoxygalactonojirimycin (NB-DGJ), reduces ganglioside biosynthesis and levels of stored GM2 in SD mice. Intracranial transplantation of Neural Stem Cells (NSCs) can provide enzymatic cross correction, to help reduce ganglioside storage and extend life. Here we tested the effect of NSCs and NB-DGJ, alone and together, on brain β-hexosaminidase activity, GM2, and GA2 content in juvenile SD mice. The SD mice received either cerebral NSC transplantation at post-natal day 0 (p-0), intraperitoneal injection of NB-DGJ (500 mg/kg/day) from p-9 to p-15, or received dual treatments. The brains were analyzed at p-15. β-galactosidase staining confirmed engraftment of lacZ-expressing NSCs in the cerebral cortex. Compared to untreated and sham-treated SD controls, NSC treatment alone provided a slight increase in Hex activity and significantly decreased GA2 content. However, NSCs had no effect on GM2 content when analyzed at p-15. NB-DGJ alone had no effect on Hex activity, but significantly reduced GM2 and GA2 content. Hex activity was slightly elevated in the NSC + drug-treated mice. GM2 and GA2 content in the dual treated mice were similar to that of the NB-DGJ treated mice. These data indicate that NB-DGJ alone was more effective in targeting storage in juvenile SD mice than were NSCs alone. No additive or synergistic effect between NSC and drug was found in these juvenile SD mice.


Hepatitis B Virus-Encoded MicroRNA (HBV-miR-3) Regulates Host Gene PPM1A Related to Hepatocellular Carcinoma.
Hepatitis B is a liver infection disease caused by the Hepatitis B Virus (HBV) that can become chronic and develop into hepatocellular carcinoma. HBV was classified as a double-stranded DNA virus. Currently, there is a report showing that HBV virus-encoded miRNA called HBV-miR-3 controls the replication of HBV. However, the regulation of HBV-miR-3 in host cells remains unclear. This study aimed to investigate the regulation of HBV-miR-3 in host gene target which is related to chronic HBV infection and HCC process. In this study, we analyzed the read count of HBV-miR-3 from next-generation sequencing of chronic hepatitis patients in Pegylated interferon alpha-2a (PEG-IFN-α-2a) treatment. To understand the regulation of HBV-miR-3 in host cells, the HBV-miR-3 recognition sites were predicted in host target genes using miRDB. The effect of HBV-miR-3 in host cells was examined using qPCR and 3' UTR dual luciferase assay. The read count of HBV-miR-3 was found in chronic hepatitis patients before treatment. Moreover, the decrease of HBV-miR-3 was correlated with response group of chronic hepatitis patients after treatment. On the other hand, the abundance of HBV-miR-3 showed no difference in nonresponse group of chronic patients after PEG-IFN-α-2a treatment. To study the role of HBV-miR-3 in patients, four HBV-miR-3 target regions from Protein phosphatase 1A (PPM1A) and DIX domain containing 1 (DIXDC1) were identified in the human genome using miRDB. Interestingly, we found that HBV-miR-3 hybridized with PPM1A mRNA. The mRNA expression from RT-qPCR showed no difference between HepG2 transfected with pSilencer_scramble or pSilencer_HBV-miR-3. However, the reporter assay showed that PPM1A mRNA was suppressed by HBV-miR-3. The protein expression of PPM1A showed a decrease in cells overexpressing HBV-miR-3. Finally, the HBV-miR-3 can promote cell proliferation in cells overexpressing HBV-miR-3. This study is the first report showed the HBV encoded miRNA can regulate host gene expression. HBV-miR-3 silenced PPM1A by inhibiting the translation process of PPM1A. The downregulation of PPM1A promotes cell proliferation related to HCC development.


Quantitative analysis of tibial subchondral bone: Texture analysis outperforms conventional trabecular microarchitecture analysis.
The aim of this study was to compare two different methods of quantitative assessment of tibial subchondral bone in osteoarthritis (OA): statistical texture analysis (sTA) and trabecular microarchitecture analysis (tMA). Asymptomatic controls aged 20-30 (n = 10), patients aged 40-50 with chronic knee pain but without established OA (n = 10) and patients aged 55-85 with advanced OA scheduled for knee replacement (n = 10) underwent knee MR imaging at 3 Tesla with a three-dimensional gradient echo sequence to allow sTA and tMA. tMA and sTA features were calculated using region of interest creation in the medial (MT) and lateral (LT) tibial subchondral bone. Features were compared between groups using one-way analysis of variance. The two most discriminating tMA and sTA features were used to construct exploratory discriminant functions to assess the ability of the two methods to classify participants. No tMA features were significantly different between groups at either MT or LT. 17/20 and 11/20 sTA features were significantly different between groups at the MT/LT, respectively (P < 0.001). Discriminant functions created using tMA features classified 12/30 participants correctly (40% accuracy; 95% confidence interval [CI], 22-58%) based on MT data and 9/30 correctly (30%,; 95% CI, 14-46) based on LT data. Discriminant functions using sTA features classified 16/30 participants correctly (53%; 95% CI, 35-71) based on MT data and 14/30 correctly (47%; 95% CI, 29-65) based on LT data. sTA features showed more significant differences between the three study groups and improved classification accuracy compared with tMA features.


A pilot study of 13N-ammonia cardiac PET imaging to assess subacute cardiotoxicity following adjuvant intensity-modulated radiotherapy for locally advanced breast cancer.
(1) Assess the feasibility of 13 N-ammonia cardiac PET (13 N-ammonia-PET) imaging in radiotherapy (RT) treatment position in locally-advanced breast cancer (LABC) patients. (2) Correlate pre-/post-RT changes in myocardial flow reserve (MFR) with the corresponding radiation heart dose. Ten left-sided LABC patients undergoing Volumetric Modulated-Arc-Therapy (VMAT) to chest wall and regional lymph nodes underwent a rest/stress 13 N-ammonia-PET at baseline and (median) 13 months post-RT. Changes in cardiac functions and coronary artery Ca2+ scoring between baseline and follow-up were correlated with average RT dose to the myocardium,3 coronary territories, and 17 myocardial segments. Eight (of 10) patients successfully completed the study. The average rest (stress) global MBF (ml.g-1.min-1) for baseline (follow-up) were 0.83 ± 0.25 (2.4 ± 0.79) and 0.92 ± 0.30 (2.76 ± 0.71), respectively. Differences in MBF, heart rate, blood pressure, and rate-pressure product (RPP) between baseline and follow-up were insignificant (P > 0.1).Strong (R = 0.79; P < 0.01) and moderate (R = 0.53; P = 0.37) correlation existed between MBF Rest and MBF Stress, and RPP respectively. Four patients showed a reduction in MFR of up to ~41% in follow-up studies, increasing to ~52% in myocardial segments close to high-radiation isodose lines in 5/8 patients. Agatston Ca + 2 scoring were zero in both baseline and follow-up in six patients; two patients exhibited mild increase in Ca + 2 on follow-ups (range:10-20).Rest and stress LVEF's were normal (>50) for all patients in both studies. The feasibility of 13 N-ammonia-PET imaging in treatment position of LABC patients was demonstrated. MFR at 1-year post-irradiation of the heart decreased in 50% of the patients. MFR may be a potential index for early detection of cardiotoxicity in BC patients receiving RT to the chest wall.


A New Fluorescence Sensor for Cerium (III) Ion Using Glycine Dithiocarbamate Capped Manganese Doped ZnS Quantum Dots.
A new fluorescence sensor for Ce(3+)ions is reported in this paper. This sensor is based on the fluorescence quenching of glycine dithiocarbamate (GDTC)-functionalized manganese doped ZnS quantum dots (QDs) in the presence of Ce(3+)ions. The synthesis of ultra-small GDTC-Mn:ZnS quantum dots (QDs) is based on the co-precipitation of nanoparticles in aqueous Solution. The nanoparticles are characterized with fluorescence spectroscopy, UV-vis absorption spectra, high-resolution transmission electron microscopy, X-ray power diffraction (XRD), and infrared spectroscopy. In the test carried out, it was found that the interaction between Ce(3+)ions and GDTC capped Mn:ZnS QDs quenches the original fluorescence of QDs according to the Stern-Volmer equation and the results show the existence of collisional quenching process. A linear relationship was observed between the extent of quenching and the concentration of Ce(3+)in the range of 2.0 × 10(-6) to 3.2 × 10(-5) mol.L(-1), with a detection limit of 2.29 × 10(-7) mol.L(-1). The relative standard deviation of 1.61% was obtained for five replicate measurements. The possible quenching mechanism was also examined by fluorescence and UV-vis absorption spectra. The interference of other cations was negligible on the quantitative determination of Ce(3+). This method proved to be simple, sensitive, low cost, and also reliable for practical applications.


Without IPv6, there is no digital transformation for healthcare.
Originally, digital healthcare was created to support underserved and rural patients gain access to health services. Phones, devices, and computers need IP (Internet Protocol) addresses to connect to the Internet. This paper aims to study the close relationship between the Internet and the transformation of healthcare services. The current protocol in use is the Internet Protocol version 4 (IPv4), whose number of Internet addresses has been globally exhausted. The Internet Protocol version 6 (IPv6) with 47 octillion unique addresses for every person on the planet has become the only option for sustainable growth and innovation. However, most of the worldwide industry is still in IPv4. In the era of Artificial Intelligence, Internet of Things, Fifth Generation of Cellular Technology (5G), and Blockchain, there will be a massive need of IP addresses. For 2025, experts predict over 1.5 billion new IPv6 users which will continue to grow exponentially. Nations need to tackle the increasing industry requirements for IPv6 and telehealth adoption to benefit from the full IPv6 connectivity which is the key strategic advantage for the healthcare industry. The strategic potential that telehealth brings to the healthcare industry is widely appreciated. However, what are the implications of its expansion around the world? How can we prioritize the poorest and most vulnerable in society without new technologies?


Sternalis muscle: importance in surgery of the breast.
Mastectomy is a commonly performed surgery for carcinoma of breast. During surgery, pectoral fascia is removed and pectoralis major muscle is laid bare. Sternalis is a rare muscle encountered in the subcutaneous plane. We examined the operative records of 1,152 patients who underwent modified radical mastectomies between 1990 and 2000. Patients who underwent conservative breast surgery or radical mastectomy were excluded. Among 1,152 patients who underwent modified radical mastectomy, eight were identified as having sternalis, a subcutaneously placed muscle oriented craniocaudally. The thickness of the muscle varied. The muscle was spared in all patients. Sternalis is a rare muscle in the subcutaneous plane. It should not be mistaken for a mass on mammography. During surgery it is important to be aware of this rare entity and identify the muscle early so that the dissection plane is appropriate. The depth at which internal mammary nodes are irradiated may also vary in the presence of the muscle. In addition, it should not be mistaken for recurrence on follow-up.


Reversibility of the changes induced by n-3 fatty acids in mouse plasma, liver and blood cell lipids.
The changes induced by dietary n-3 fatty acids (FA) in the lipids and FA of plasma, liver and blood cells, and their reversibility, was studied in mice given a diet containing 9% fish oil (FO) for 2 weeks and then returned to, and kept for another 2 weeks on, the usual standard lab chow diet. In plasma, the concentrations of phospholipids (PL), mostly phosphatidylcholine (PC), triacylglycerols (TG), cholesterol and cholesterol esters (CE) decreased rapidly after starting the FO diet, and remained low from day 3 onwards. This decrease was concomitant with a remarkable reduction in the n-6 FA, especially 18:2n-6, not compensated for by the relative enrichment in n-3 FA induced by FO. In liver, TG and CE decreased and PL slightly increased, all of them showing reduced n-6/n-3 ratios. Sphingomyelin, which lacks polyunsaturated FA other than small amounts of 18:2 and 24:2n-6, showed altered ratios between its very long chain monoenes and saturates. In the washout phase, the most rapid event was an immediate increase in 18:2n-6 and after a few days in 20:4n-6 in plasma and liver, where most of the lipid and FA changes were reversed completely in about 10 days. In the case of blood cells even 2 weeks were insufficient for a reversal to the initial n-6/n-3 ratios. The lipid class responsible for this lack of reversibility was phosphatidylethanolamine, PC having returned to the initial fatty acid composition during the stated period.


Associations between self-estimated and measured physical fitness among 40-year-old men and women.
The aim was to evaluate whether 40-year-old men and women are able to estimate their level of fitness compared with actual measured physical fitness. Twenty-nine men and 35 women first completed a questionnaire at home and then their physical fitness was measured at laboratory. The index of self-estimated physical fitness was calculated by summing up the scores of self-estimated endurance, strength, speed and flexibility. The index of self-estimated endurance was calculated by summing up the scores of self-estimated endurance and those of the self-estimated distance they could run, cycle, ski and walk. The index of measured physical fitness was calculated by summing up the z-scores of a submaximal bicycle ergometer test, ergojump tests (counter-movement jump and jumping in 15 s), a 30-s sit-up test, hand-grip tests and a sit-and-reach test. The correlation (Spearman) between the indices of self-estimated and measured physical fitness was 0.54 for both sexes, and that between self-estimated endurance and measured endurance was 0.53 for both sexes. Maximal oxygen uptake estimated based on submaximal ergometer test was higher among those with longer self-estimated distance of running, cycling, skiing and walking (P for linear trend <0.001). Our study shows that 40-year-old adults can estimate at group level their fitness according to different categories moderately well. They can also estimate at group level their endurance moderately well by estimating the distance they can run, cycle, ski or walk. However, in some individuals self-estimation of fitness is not in agreement with the results of fitness tests.


Power production strategy during steady-state cycling is cadence dependent.
Crank power is produced by extension and flexion of the hip and knee joints during steady-state pedaling below 120 rpm. Despite the pedaling cadence exceeding 120 rpm during track cycling, the power production strategy for lower-limb coordination above 120 rpm is unknown. This study aimed to assess the effects of various pedaling cadences on the power production strategy of lower-limb coordination during steady-state pedaling. Twenty trained collegiate cyclists performed a 30-s steady-state pedaling exercise at 50% of maximal anaerobic power under four different conditions with 90-, 120-, 150- and 180-rpm pedaling cadences. Pedal kinetics and limb kinematics were recorded using a pedal force measurement system and motion capture system, respectively. Positive mechanical work of hip extension significantly decreased with increasing pedaling cadence (P < 0.05). In contrast, the positive mechanical work of the knee joint flexion significantly increased with increasing pedaling cadence (P < 0.05). For contribution to the total mechanical work at 150 or above rpm, the knee joint showed > 70% of the total contribution, whereas the hip joint showed < 40%. Additionally, the positive mechanical work of the hip shifted to negative mechanical work under 180-rpm condition. These results indicate that power production strategy during steady-state pedaling at 180 rpm is different from the general pedaling cadence. Therefore, specific training needs to be conducted at an excessive-high pedaling cadence such as 180 rpm to achieve high performance in track cycling.


Effectiveness of a programme comprising serial casting, botulinum toxin, splinting and motor training for contracture management: a randomized controlled trial.
To determine the effectiveness of a programme comprising serial casting, botulinum toxin, splinting and motor training in contracture management. A randomized trial with concealed allocation and assessor blinding, a deferred treatment cross-over design within the control group, was conducted. Inpatient Brain Injury Unit of a rehabilitation centre. A total of 10 patients with severe acquired brain injury (13 ankles). The intervention group received botulinum toxin and then serial casting. The control group was placed on a wait list for six weeks (control phase) and then received the same interventions as the intervention group (intervention phase). Both groups received splinting and motor training following serial casting. The primary outcome was passive ankle dorsiflexion range. Secondary outcomes included spasticity, ankle dorsiflexor strength, Functional Independence Measure score for the walking item and walking speed. The mean between-group difference for passive ankle dorsiflexion range at completion of casting was 26° (95% confidence interval (CI): 17-35); at Week 2, after casting was 24° (95% CI: 14-33). The mean within-group differences for passive ankle dorsiflexion at completion of casting, Week 2 after casting and Week 8 after casting were 26° (95% CI: 20-31), 26° (95% CI: 18-33) and 24° (95% CI: 19-30), respectively. These improvements were sustained at Week 2 and Week 8 after casting. A programme for contracture management comprising serial casting, botulinum toxin, motor training and splinting can be useful in improving joint range.


Accumulation and elimination of dieldrin in muscle tissue of channel catfish.
Dieldrin accumulation and elimination in muscle tissue of channel catfish (Ictalurus punctatus) from water and food was determined in the laboratory. Twenty-eight-day exposure of fish 150-225 mm and 350-400 mm long to 75 parts per trillion (ng/liter) dieldrin resulted in the larger catfish consistently accumulating more dieldrin than the smaller fish. After 28 days of elimination, dieldrin levels in both size groups were nearly equal. Catfish exposed to 2 ppm (mg/kg) dieldrin through their diets accumulated significantly more dieldrin in muscle than did fish exposed to 75 pptr in water. When fish were exposed to dieldrin both in food and water, dieldrin from both sources contributed to the total dieldrin load. Large catfish accumulated more dieldrin from food and water than did smaller catfish. After 28 days of elimination, levels of dieldrin were not significantly different in muscles of 150-225 mm and 350-440 mm catfish exposed via both food and water.


[Hermann Emminghaus--100 years of the psychopathology of childhood and adolescence].
The centenary of Hermann Emminghaus's monograph "Die psychischen Störungen des Kindesalters" ("The Psychic Disorders of Childhood") gives occasion to appreciate the life and work of the founder of modern children and youth psychiatry. Children and youth psychiatry, in the G.D.R., operates on the principle of sub-specialization out of its parent subjects. In this, Hermann Emminghaus's basic views, as expressed in his monograph of 1887, are confirmed.


Effect of emodin on endoplasmic reticulum stress in rats with severe acute pancreatitis.
This study aimed to investigate the protective effect of emodin on endoplasmic reticulum (ER) stress in rats with severe acute pancreatitis (SAP) and the underlying molecular mechanism. Sprague-Dawley male rats were randomly divided into sham operation group, SAP model group, and emodin treatment group. SAP was constructed through injecting sodium taurocholate into pancreatic and biliary duct in rats. Half an hour before establishing the animal model, emodin or sodium carboxymethylcellulose was intragastrically administrated to the rats in respective group. Rats were killed at 3, 6, and 12 h postdisease induction. The amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in serum, pancreatic histopathology, acinar ER ultrastructure, protein expression of Bip, IRE1α,TRAF2, ASK1, p-JNK, and p-p38 MAPK in pancreas were examined. Sodium taurocholate induced pancreatic injury and ER lumen dilated in exocrine pancreas in rats at 3-, 6-, and 12-h time points. ER stress transducers Bip, IRE1α, and their downstream molecules TRAF2, ASK1 in pancreatitis were upregulated. Furthermore, phosphorylation of JNK and p38MAPK in pancreas was increased, which induced high expression level of inflammatory cytokines such as TNF-α and IL-6. Treatment with emodin obviously ameliorated pancreatic injury and decreased the release of amylase and inflammatory cytokines. Further studies showed that emodin significantly decreased the expression of Bip, IRE1α, TRAF2, and ASK1, inhibited phosphorylation of JNK and p38 MAPK in pancreas in rats at all time points. Emodin could reduce pancreatic injury and restrain inflammatory reaction in SAP rats partly via inhibiting ER stress transducers IRE1α and its downstream molecules.


Ocular manifestations of diabetes mellitus: diabetic cataracts in dogs.
Cataracts form in diabetic dogs because of the disruption of normal lens metabolism. The pathophysiology seems to be a combination of increased lens cell membrane permeability, reduced cell membrane function, damage from accumulating osmotic products (polyols), glycosylation of lens proteins, and oxidative injury. Lens-induced uveitis must be recognized and managed in presurgical preparation of dogs with diabetes cataracts. Phacoemulsification is the current treatment of choice for diabetic cataracts in dogs and can be performed at an earlier time than traditional extracapsular lens extraction. This may allow for greater success rates after surgery.


Should predictive scores based on vital signs be used in the same way as those based on laboratory data? A hypothesis generating retrospective evaluation of in-hospital mortality by four different scoring systems.
few studies have compared the discrimination of predictive scores of in-hospital mortality that used vital signs with those using laboratory results in different patient populations. a hypothesis generating retrospective observational cohort study. A score that only used vital signs was compared with three other scores that used laboratory changes in 44,985 medical and 20,432 surgical patients. the discrimination of the score based only on vital signs was highest for the prediction of in-hospital death within 24h. In contrast the, albeit lower, discrimination of scores based only on laboratory data remained constant for the prediction of death up to 30 days after hospital admission. Moreover, the discrimination of scores based only on laboratory data was higher in surgical than in medical patients. in acutely ill medical patients a vital sign based score appears to predict mortality within 24h better than scores using laboratory data. This may be because in acutely ill patients vital sign changes indicate how well a patient is responding to a current insult. In contrast, for patients without acute illness laboratory data may be a more valuable indication of the patient's capacity to respond to insults in the future.


Compound heterozygote for lipoprotein lipase deficiency: Ser----Thr244 and transition in 3' splice site of intron 2 (AG----AA) in the lipoprotein lipase gene.
Cloning and sequencing of translated exons and intron-exon boundaries of the lipoprotein lipase gene in a patient of French descent who has the chylomicronemia syndrome revealed that he was a compound heterozygote for two nucleotide substitutions. One (TCC----ACC) leads to an amino acid substitution (Ser----Thr244), while the other alters the 3' splice site of intron 2 (AG----AA). The functional significance of the Thr244 amino acid substitution was established by in vitro expression in cultured mammalian cells.