[Preparation and degradation characteristics of bone repair composite--PDLLA/HA/DBM].
To explore a new method of preparing the composite of DL-polylactic acid (PDLLA), hydroxyapatite(HA), decalcium bone matrix (DBM), and to observe the degradation characteristics of PDLLA/HA/DBM in vitro. An emulsion blend method was developed to prepare the composite of PDLLA/HA/DBM based on the weight rate of PDLLA:HA:DBM = 1.5-2:1-1.5:1. The characteristics of the particles was observed by scanning electron microscope. In vitro, PDLLA/HA/DBM and PDLLA were put into PBS(pH7.4) respectively; the pH value, weight and biomechanics of them were determined during the degradation. Without heating, the emulsion blend method could be developed to prepare PDLLA/HA/DBM. Scanning electron microscope showed that the gap diameter in the compound material was 100 to 400 microns, and the porosity was 71.3%; During degradation, the pH value of PDLLA decreased little within 2 weeks, then decreased obviously and decreased to 4.0 at the end of the 4th week; while the pH value of PDLLA/HA/DBM kept quite steady and was 6.4 at the end of the 12th week. The weight of PDLLA decreased little within 4 weeks, then decreased obviously and remained 50% of its prime weight at the end of the 12th week; while the weight of PDLLA/HA/DBM decreased little within 5 weeks, then decreased obviously and remained 60% of the prime at the end of the 12th week. The prime biomechanical strength was 1.33 MPa in PDLLA and 1.71 MPa in PDLLA/HA/DBM. There was significant difference between them (P < 0.05). The strength of PDLLA decreased little within 3 weeks, then decrease obviously and was 0.11 MPa at the end of the 12th week; the strength of PDLLA/HA/DBM decreased little within 4 weeks, then decrease obviously and was 0.21 MPa at the end of the 12th week. The emulsion blend method is a new method to prepare bone repair materials. As a new bone repair material, PDLLA/HA/DBM is suitable for bone tissue engineering for its good characteristics of porosity and degeneration.


Barrett's esophageal cancer in which magnifying narrow-band imaging was useful for diagnosing extension under the squamous epithelium.
A 36-year-old man complained of heartburn. Gastrointestinal endoscopies showed a reddish and slightly depressed lesion in the right-anterior wall of the esophagogastric junction. With white light imaging, the area of the adenocarcinoma under the squamous epithelium was difficult to detect, but a slightly flat, elevated lesion appeared in the area of adenocarcinoma under the squamous epithelium. With narrow-band imaging (NBI) in the area of the Barrett's esophageal cancer under the squamous epithelium, a slight, brownish change could be observed. In addition, with the magnifying technique, irregular mesh-like vessels were observed, suggesting the presence of differentiated adenocarcinoma under the squamous epithelium. The lesion was resected en bloc by endoscopic submucosal dissection, and Barrett's esophageal cancer under the squamous epithelium was histologically confirmed. In this case, NBI with magnifying endoscopy was very useful to diagnose the extension of Barrett's esophageal cancer under the squamous epithelium.


Principal component analysis for protein folding dynamics.
Protein folding is considered here by studying the dynamics of the folding of the triple beta-strand WW domain from the Formin-binding protein 28. Starting from the unfolded state and ending either in the native or nonnative conformational states, trajectories are generated with the coarse-grained united residue (UNRES) force field. The effectiveness of principal components analysis (PCA), an already established mathematical technique for finding global, correlated motions in atomic simulations of proteins, is evaluated here for coarse-grained trajectories. The problems related to PCA and their solutions are discussed. The folding and nonfolding of proteins are examined with free-energy landscapes. Detailed analyses of many folding and nonfolding trajectories at different temperatures show that PCA is very efficient for characterizing the general folding and nonfolding features of proteins. It is shown that the first principal component captures and describes in detail the dynamics of a system. Anomalous diffusion in the folding/nonfolding dynamics is examined by the mean-square displacement (MSD) and the fractional diffusion and fractional kinetic equations. The collisionless (or ballistic) behavior of a polypeptide undergoing Brownian motion along the first few principal components is accounted for.


Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases.
We investigated the occurrence of T cells in the brain parenchyma of Alzheimer's disease (AD), non-AD degenerative dementias and controls by semi-quantitative analysis of immunohistochemically stained tissue sections. In all cases, we found at least some T cells. The number of T cells was increased in the majority of AD cases compared with other cases. The phenotype of T cells in the AD brain indicates that they are activated but are not fully differentiated. Antigen-triggered clonal expansion is not likely to take place. Local inflammatory conditions might cause accumulation and activation of T cells in the AD brain.


[Standardization of implants shown by "bone-screws" (author's transl)].
The increasing use of orthopaedic implants makes international efforts of standardization with their objectives unification and benefit of the patient necessary and sufficient. In 1975 an ISO-Draft for "bone-screws" has been finished. To get experimental data there was a test series of breaking bone-screws of five producers by torsional stress. Comparable screws showed considerable differences. The control of conformity to standards gave partially distinct differences to the standard profile and different hardness values, what affects to the screws' security of twisting off.


Biodegradable wound dressing-based collagen/hyaluronic acid loaded antibacterial agents for wound healing application.
Three biodegradable wound dressing based on binary Collagen (COL), Hyaluronic acid (HA) crosslinked loaded with silver nanoparticles (AgNPs), Gentamicin (GENT) and AgNPs/GENT successfully prepared using freeze drying technique. Chemical evaluations for synthesized membranes were carried out using FTIR- ATR. While physical properties were evaluated through swelling and degradation percent. Antibacterial activity was evaluated against G+, G-, yeast and fungi. Finally, cytotoxicity and wound healing evaluations were carried out against skin fibroblast normal cell line, while anti-inflammatory evaluated using RAW 264.7 macrophage cell line. The three produced membrane showed physically interaction between polymer network and the loaded antibiotic. Swelling properties showed superior results for three membranes. Degradability of prepared sheets was rapidly no more than three days. Toxicity evaluations and anti-inflammatory showed superior results for all examined samples except mixed with AgNPs and Gentamicin (GENT). Antibacterial activity showed resistance to G+, G- and yeast. All prepared sheet showed safe towards cell except COL/HA/AgNPs/GENT. Wound healing studied showed efficient of both COL/HA/AgNPs and COL/HA/GENT compared to blank and mixed membrane COL/HA/AgNPs/GENT. The obtained results recommended COL/HA loaded individually either AgNPs or Gentamicin (GENT) as antibacterial and wound healing sheet rather than mixed prepared membrane.


Guidance by odors in honeybee navigation.
Animal navigation is guided by multiple sensory cues. Here, we ask whether and how olfactory stimuli emanating from places other than the trained feeding site redirect the flight paths of honeybees. The flight trajectories of individual bees were registered using harmonic radar tracking. Sensory cues (compass direction, distance, visual cues en route and close to the feeding site) associated with the trained flight route dominated wayfinding, but a learned odorant carried by air flow induced excursions into the wind. These redirections were largely restricted to rather small deviations from the trained route (<60°, <200 m) and occurred only if the animal did not receive the trained odorant stimulus at the trained feeding site. Under certain conditions, larger excursions were observed. These findings are discussed in the context of odor guidance of honeybees over longer distances (>300 m from the hive).


Blue-Native Electrophoresis to Study the OXPHOS Complexes.
Blue-native polyacrylamide gel electrophoresis (BN-PAGE) is a technique optimized for the analysis of the five components of the mitochondrial oxidative phosphorylation (OXPHOS) system. BN-PAGE is based on the preservation of the interactions between the individual subunits within the integral complexes. To achieve this, the complexes are extracted from the mitochondrial inner membrane using mild detergents and separated by electrophoresis in the absence of denaturing agents. The electrophoretic procedures can then be combined with a variety of downstream detection techniques. Since its development in the 1990s, BN-PAGE has been applied in the study of mitochondria from all kinds of organisms and extensive amounts of data have been produced using this technique, being key for the understanding of many aspects of OXPHOS physiopathology.


Polycyclic Indoline Derivatives by Dearomatizing Anionic Cyclization of Indole and Tryptamine-Derived Ureas.
The base-promoted dearomatizing cyclization of anionic indole-containing urea derivatives provided tri- or tetracyclic indoline-containing scaffolds from lithiated urea intermediates. 3-Substituted indoles, including tryptamine derivatives, generally underwent the reaction in high yield and with excellent diastereoselectivity. In situ IR spectroscopy suggests a deprotonation-carbolithiation-reprotonation mechanism.


Modulation of endomorphin-2-induced analgesia by dipeptidyl peptidase IV.
The tetrapeptide, endomorphin-2 (Tyr-Pro-Phe-PheNH2) possesses high affinity for mu opioid receptors, and produces potent analgesia in mice. Its structure appears to satisfy the substrate requirements of the proteinase, dipeptidyl peptidase IV which removes dipeptides from the amino terminus of peptides containing proline as the penultimate amino acid. A potent, stable and specific inhibitor of this enzyme, Ala-Pyrrolidonyl-2-nitrile, has been described which should potentiate endomorphin-2-induced analgesia. Further, since dipeptidyl peptidase IV has an absolute requirement for l-Pro, a more metabolically-stable d-Pro2-endomorphin-2 analog should produce longer analgesic actions at lower doses. The present study found that endomorphin-2 was degraded approximately twice as fast than the chromogenic substrate, Ala-Pro-2naphthylamide, by dipeptidyl peptidase IV, whereas d-Pro2-endomorphin-2 was totally resistant to this enzyme's action. d-Pro2-endomorphin-2 (ED50=0.05 microg) was more potent than endomorphin-2 (ED50=30 microg) in significantly increasing tail-flick latencies with longer durations of action. Both the peptide and analogue were equipotent (ED50=0.5 microg) in significantly increasing jump thresholds. Ala-Pyrrolidonyl-2-nitrile (10-75 nmol) elicited a dose-dependent analgesia, and potentiated the analgesic actions of endomorphin-2, particularly on the tail-flick test. Whereas systemic naltrexone (2.5, 10 mg/kg) dose-dependently eliminated each of the three forms of analgesia on the jump test as well as the peak (15 min) effect on the tail-flick test, analgesia elicited by either endomorphin-2, d-Pro2-endomorphin-2 or Ala-Pyrrolidonyl-2-nitrile returned after 30-60 min in naltrexone-treated rats on the tail-flick test. These data strongly suggest that dipeptidyl peptidase IV plays a role in the inactivation of endomorphin-2 in vivo, and thereby modulates its central analgesic actions.


Fractionated extract of Astragalus membranaceus, a Chinese medicinal herb, potentiates LAK cell cytotoxicity generated by a low dose of recombinant interleukin-2.
Success with rIL-2 immunotherapy of human cancer appears to depend on the administration of high doses which are frequently associated with excessive toxicity. Future use of rIL-2 will require certain modifications based on the use of lower doses of rIL-2 without significant loss of antitumor efficacy. We tested in vitro the possibility of potentiating the activity of rIL-2 in terms of LAK cell generation. We hypothesized that co-incubation of LAK cell precursors with a Chinese herbal extract (F3) of Astragalus membranaceus, (an immune modulator currently under study in our laboratory), along with a low concentration of rIL-2, would generate levels of LAK cell activity equivalent to those generated by high concentrations of rIL-2 alone. We found (1) a 10-fold potentiation of rIL-2 activity manifested by tumor cell-killing activity of 80% resulting from LAK cell generation with F3 plus 100 u/ml of rIL-2 versus 76% generated by 1,000 u/ml of rIL-2 alone; (2) a significant reduction in the number of effector LAK cells required for equicytotoxic reaction following LAK cell generation with F3 plus rIL-2 compared to rIL-2 alone. We conclude that potentiation of antitumor activity mediated by rIL-2 in low concentrations is possible by the concomitant use of another immune modulator such as Astragalus membranaceus.


7a-Phenyl-tetra-hydro-pyrrolo-[2,1-b]oxazol-5(6H)-one.
In the title compound, C12H13NO2, the pyrrolidinone moiety is almost flat while the oxazole ring adopts an envelope conformation with the carbon atom bearing the phenyl substituent as the flap: the angle between the mean planes of the fused heterocyclic rings is 45.47 (19)°. In the crystal, C-H⋯O and C-H⋯π contacts link the mol-ecules into infinite [010] chains.


Research progress on the basic helix-loop-helix transcription factors of Aspergillus species.
Basic helix-loop-helix (bHLH) proteins belong to a superfamily of transcription factors, and they are widely distributed in eukaryotic organisms. Members of the bHLH protein family can form homodimers or heterodimers with themselves or other family members, and they often play bifunctional roles as activators and repressors to uniquely regulate the transcription of downstream target genes. The bHLH transcription factors are usually involved in developmental processes, including cellular proliferation and differentiation. Therefore, these transcription factors often play crucial roles in regulating growth, development, and differentiation in eukaryotes. Aspergillus species fungi are widely distributed in the environment, and they play important roles not only in the decomposition of organic matter as an important environmental microorganism but also in the fermentation and the food processing industry. Furthermore, some pathogenic fungi, such as Aspergillus flavus and Aspergillus fumigatus, affect the environment and human health in important ways. Recent research has shown that some Aspergillus bHLH proteins are significantly involved in the regulation of asexual and sexual reproduction, secondary metabolite production, carbohydrate metabolism, conidial and sclerotial production, among other processes. Here, we review the regulatory mechanisms and biological functions of the bHLH transcription factors of the Aspergillus genus to provide a theoretical reference for further study on the growth and development of Aspergillus and the functions of bHLHs.


Streptococcus milleri infection of a hepatopulmonary hydatid cyst.
A case of hepatopulmonary hydatid disease in a Cypriot who presented with pyogenic infection with Streptococcus milleri is described. Although hydatid disease and pyogenic liver abscess are both rare in the UK, an underlying echinococcal pathology should be suspected in any patient from an area endemic for hydatid who presents with a pyogenic hepatic or hepatopulmonary abscess.


Skeletal Muscle Dysfunction in People With Multiple Sclerosis: A Physiological Target for Improving Physical Function and Mobility.
Impaired mobility is amongst the most debilitating symptoms reported by people with multiple sclerosis (MS). Historically, it has been viewed that walking impairments in people with MS are directly caused by the physical damage to the neurons in the central nervous system (CNS) which results from the immunopathology of MS. However, research from over the past 4 decades has revealed that physical function in people with MS is also affected by skeletal muscle dysfunction characterized by a reduced capacity to produce, regulate, and sustain the force-generating muscle contractions that propel human movement. While the immediate CNS damage caused by MS can alter the neural activation of muscle by disrupting neuromotor transmission, chronic reductions in mobility and extreme fatigue can lead to physically inactive lifestyles that negatively affect skeletal muscle through mechanisms of deconditioning. Consequently, people with MS can experience alterations in activation patterns, muscle mass and tissue composition, contractility, metabolism, and perfusion that contribute to reductions in muscle function that ultimately impair key physical functions such as walking. This article provides an overview of the cellular mechanisms that contribute to skeletal muscle dysfunction in people with MS and a discussion of the current evidence suggesting that skeletal muscle may be a key physiological target for interventions aiming to improve mobility in this population. We specifically highlight recent evidence demonstrating the potential for rehabilitation and exercise interventions to induce muscle plasticity in people with MS who have moderate to severe levels of disability. In conclusion, we discuss future directions in basic science and clinical research that may advance our understanding of muscle dysfunction in MS and lead to the development of more precise and effective treatment strategies.


Transcatheter interatrial septal defect closure in a large cohort: midterm follow-up results.
We evaluated immediate and midterm results of transcatheter closure of atrial septal defects (ASDs) and patent foramen ovale (PFO) using various closure devices. The study included four hundred fourteen patients (one hundred eighty-two men, two hundred thirty-two women; mean age 39 ± 12.3 years; range 17-67 years) who underwent transcatheter closure of secundum ASD (n = 193) or PFO (n = 221). All the patients were evaluated by transthoracic echocardiography and transesophageal echocardiography before the procedure. Transcatheter closure was performed by using Amplatzer (n = 184), Occlutech Figulla (n = 209), or BioSTAR (n = 21) devices. Closure of ASDs was performed under general anesthesia with transesophageal echocardiography guidance, and closure of PFOs was performed under local anesthesia with transthoracic echocardiography guidance. Follow-up controls were at 1, 6, and 12 months and annually thereafter. The median follow-up periods of ASD and PFO patients were 43 and 30 months. The mean device size was 19.3 ± 6.2 mm for ASD patients and 24.6 ± 2.6 mm for PFO patients. The mean procedural and fluoroscopy times were 22.3 ± 4.7 and 4.1 ± 1.9 minutes for ASD closure and 12.4 ± 3.2 and 3.1 ± 1.2 minutes for PFO closure, respectively. Procedural device embolization occurred in only two patients (0.48%). During follow-up, recurrent embolic events occurred in four patients (1.8%) after PFO closure, and no residual shunts were seen after ASD closure. Device thrombosis developed in two ASD patients during the procedure and in one PFO patient at 12th month of the follow-up (0.72%). Transcatheter closure of PFOs and secundum-type ASDs using the Amplatzer, Occlutech Figulla, and BioSTAR devices is an efficacious and safe therapeutic option.


Platinum(0) olefin complexes of a bulky terphenylphosphine ligand. Synthetic, structural and reactivity studies.
A novel terphenylphosphine PMe2Ar(Dipp2) () (Dipp = 2,6-(i)Pr2C6H3) forms stable Pt(0) complexes with ethene and 3,3-dimethylbut-1-ene that behave as sources of the reactive Pt(PMe2Ar(Dipp2)) fragment. The complexes are efficient catalysts for the selective hydrosilylation of terminal alkynes.


Urothelial leukoplakia: new aspects of etiology and therapy.
We describe 3 women in 1 family who had systemic urothelial leukoplakia with no underlying pathological condition of the urinary tract. Irritative clinical symptoms resolved, and the macroscopic and microscopic appearance improved after 6 months of therapy with sodium pentosanpolysulfate. Electron microscopy showed special cells in the basal layer of the cornified squamous epithelium that also have been found in the trigone of women with so-called squamous metaplasia. Their similarity to Merkel's cells of the skin supports the theory that ectodermal cells are misplaced during embryogenesis. Genetic factors and sex hormones seem to influence the development of certain variants of squamous epithelium within the urinary tract.


Radiation dose-volume effects on growth hormone secretion.
Growth hormone (GH) deficiency is a known consequence of central nervous system irradiation. The relationship between the dose to the hypothalamus and the time to onset of clinically significant GH deficiency is unknown. Conformal radiotherapy (CRT) techniques allow for a more accurate determination of hypothalamic dosimetry. We correlated the dosimetry of the hypothalamus and the peak GH value after CRT in children with localized primary brain tumors. The arginine tolerance/L-dopa test was performed before (baseline) and repeated 6 and 12 months after CRT in 25 children (median age 4.8 years) with ependymoma (n = 15) or low-grade (n = 8) or high-grade (n = 2) astrocytoma. None had evidence of GH deficiency (arginine tolerance/L-dopa peak GH level >10 ng/mL [10 microg/L]) at baseline. Peak GH levels were modeled as a function of time after CRT and volume of the hypothalamus receiving a dose within the specified intervals of 0-20 Gy, 20-40 Gy, and 40-60 Gy. The model was used to predict the change in the peak GH levels over time (0-12 months) and fit under the assumption that the integral effect of irradiation was a linear sum of the products of the volume receiving a particular dose and the impact of that dose. The peak GH level declined during the 0-12 months after CRT (p < 0.0001). GH deficiency was observed in 11 children at 6 months and a total of 20 children at 12 months. As expected, the effect of the dose interval 0-20 Gy was smaller than the 20-40-Gy dose interval; the largest effect was noted with the dose interval 40-60 Gy. The peak GH level may be predicted using the following estimating equation within the time limit of 0-12 months: GH(t)=Exp[ln(bGH)-(0.00058V(0-20 Gy)+0.00106V(20-40 Gy)+0.00156V(40-60 Gy))x t], where bGH is the baseline peak GH level, V(0-20 Gy), V(20-40 Gy), and V(40-60 Gy) is the percent-volume of the hypothalamus irradiated from 0 to 20 Gy, 20 to 40 Gy, and 40 to 60 Gy, respectively, and t is time after irradiation. When included in the model, the rate of decline in the peak GH response also was influenced by hydrocephalus and tumor location. The peak GH response within 12 months after CRT depends on hypothalamic dose-volume effects and may be predicted on the basis of a linear model that sums the effects of the entire distribution of dose. The modeled effects may be used to optimize radiotherapy and minimize and treat GH deficiency.


Association between ossification of the posterior longitudinal ligament and ossification of the nuchal ligament in the cervical spine.
To investigate the association between ossification of the posterior longitudinal ligament (OPLL) and ossification of the nuchal ligament (ONL) in terms of incidence and size. This retrospective study evaluated 297 patients who underwent CT of the cervical spine (C-spine). Two radiologists worked in consensus. The incidence of OPLL from patients with and without ONL was compared using Chi Square tests. The mean lengths of ONL from patients with and without OPLL were compared using Student t-test. The correlations between the length of ONL and the presence of OPLL and between the length of ONL and the length of OPLL were analyzed with Pearson correlations. We found that OPLL occurred more frequently in patients with ONL than in patients without ONL (odd ratio = 2.524, p = 0.037); however, the mean length of ONL did not differ significantly patients with and without OPLL (p = 0.874). We found no significant correlation between the length of ONL and the length of OPLL (p = 0.233). The presence of ONL was associated with the presence of OPLL. The length of OPLL and ONL showed no correlation.


Investigation of the activity of baicalein towards Zika virus.
Zika virus (ZIKV) is a mosquito transmitted virus spread primarily by Aedes species mosquitoes that can cause disease in humans, particularly when infection occurs in pregnancy where the virus can have a significant impact on the developing fetus. Despite this, there remains no prophylactic agent or therapeutic treatment for infection. Baicalein is a trihydroxyflavone, that is found in some traditional medicines commonly used in Asia, and has been shown to have several activities including antiviral properties. Importantly, studies have shown baicalein to be safe and well tolerated in humans, increasing its potential utilization. This study sought to determine the anti-ZIKV activity of baicalein using a human cell line (A549). Cytotoxicity of baicalein was determined by the MTT assay, and the effect on ZIKV infection determined by treating A549 cells with baicalien at different time points in the infection process. Parameters including level of infection, virus production, viral protein expression and genome copy number were assessed by flow cytometry, plaque assay, western blot and quantitative RT-PCR, respectively. The results showed that baicalein had a half-maximal cytotoxic concentration (CC50) of > 800 µM, and a half-maximal effective concentration (EC50) of 124.88 µM. Time-of-addition analysis showed that baicalein had an inhibitory effect on ZIKV infection at the adsorption and post-adsorption stages. Moreover, baicalein also exerted a significant viral inactivation activity on ZIKV (as well as on dengue virus and Japanese encephalitis virus) virions. Baicalein has now been shown to possess anti-ZIKV activity in a human cell line.


What do mice select for in seeds?
Knowledge of the basis upon which granivores select seeds is crucial to the understanding of granivory. In this study the preferences of three rodent granivores among seeds of 11 plants from the semi-arid Karoo of South Africa were estimated, and related to the physical and chemical attributes of the seeds. Seed weights and calorific, moisture, protein, polyphenol, ash, lipid and silica contents were estimated and cell contents, soluble ash and soluble carbohydrate contents were derived from these values. These attributes were determined for both the intact seeds and the portion of the seed that is ingested by the mice. The efficiency with which mice ingested the seeds (in terms of time and mass) was recorded. All three mouse species ranked the seeds similarly, and the two species for which handling efficiency was measured did not differ in this regard. Preference hierachies were highly correlated with the rate of energy intake, as predicted by optimal foraging theory. There was no correlation between rodent preferences and the gross energy content of the seeds, emphasising the importance of measuring relevant parameters. The energy yield of the seeds calculated here, in conjunction with rodent population energy requirements and dietary data, may be used to estimate potential granivore impact on the seed production of the plant community.


Oral Incompetence: changes in speech intelligibility following facial nerve paralysis.
Speech may be compromised following facial nerve paralysis (FNP), depending on the cause of the paralysis. This can result in lower quality of life and a reduced capacity to return to vocational roles. Despite its prevalence, it is incompletely understood and rarely described. This study prospectively evaluated the impact of FNP on speech intelligibility. This observational study recruited patients who were diagnosed with FNP and who reported oral incompetence from the Sydney Facial Nerve Service. Their speech was analysed using patient reported outcome measures (Speech Handicap Index) and perceived intelligibility (Speech Pathologist, community member control participants, participant self-rating, and dictation software). Forty participants with FNP and 40 controls were recruited. Participants with FNP rated their intelligibility to be significantly worse than other raters (p <0.001). Consonant analysis demonstrated bilabial, fricatives and labiodental phonemes to be most commonly affected following FNP. Oral competence is compromised after FNP which can lead to a poorer perception of their intelligibility and reduced speech related quality of life.


MODIFIED MUBARAK TECHNIQUE FOR FLEXIBLE FLATFOOT CORRECTION IN CHILDREN AND ADOLESCENTS.
To describe the technique, analyze possible radiographic correction and evaluate the clinical result of medial and plantar calcaneal displacement osteotomy associated with opening wedge cuboid osteotomy for flexible flatfoot correction. 23 patients (30 feet) diagnosed with flexible flat foot treated with plantar and medial calcaneal displacement osteotomy associated with opening wedge cuboid osteotomy were evaluated retrospectively. In the lateral radiographs calcaneal pitch and Meary's angle were the radiographic parameters evaluated; while the talonavicular coverage angle was evaluated in the anteroposterior radiographs. To assess the clinical outcome of the surgical procedure, the American Orthopedic Foot and Ankle Society Score (AOFAS) for the ankle and hindfoot was adopted. The mean values of the evaluated angles and AOFAS score for ankle and hindfoot significantly improved when comparing pre- and postoperative values. Plantar and medial calcaneal displacement osteotomy associated with an opening wedge cuboid osteotomy is able to improve radiological and clinical parameters of child patients with flexible flatfoot. Level of Evidence III, Retrospective Comparative Study.


The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma.
We examined the effect of airway inflammation on airway remodeling and bronchial responsiveness in a mouse model of allergic asthma. BALB/c mice were sensitized to ovalbumin (OA), and exposed to aerosolized OA (0.01, 0.1 and 1%). Twenty-four hours after the final antigen challenge, bronchial responsiveness was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out. Repeated antigen exposure induced airway inflammation, IgE/IgG1 responses, epithelial changes, collagen deposition in the lungs, subepithelial fibrosis associated with increases in the amount of transforming growth factor (TGF)-beta1 in BAL fluid (BALF), and bronchial hyperresponsiveness to acetylcholine. The number of eosinophils in BALF was significantly correlated with TGF-beta1 production in BALF and the amount of hydroxyproline. Furthermore, significant correlations were found between these fibrogenic parameters and the bronchial responsiveness. These findings demonstrated that in this murine model airway eosinophilic inflammation is responsible for the development of airway remodeling as well as bronchial hyperresponsiveness in allergic bronchial asthma.


Hemodynamic effects of slow and rapid defibrination with defibrizyme, the thrombin-like enzyme from venom of the timber rattlesnake.
The hemodynamic response to slow and rapid defibrination was sutdied in anesthetized beagle dogs, with the following results: 1. Slow defibrination was a benign procedure that had little or no effect on the hemodynamic variables studied. 2. Rapid defibrination induced statistically significant decreases in cardiac output, stroke volume, and mean aortic arterial pressure. 3. Bradycardia, a drop in mean left v"ntricular pressure, cardiac and minute work indices, an increase in pulmonary artery pressure, and a drastic rise in pulmonary and systemic vascular resistances were also observed. Although physiologically apparent, these changes were not statistically significantly different from control levels. 4. Pulmonary capillary wedge pressure, left ventricular end-disatolic pressure, arterial pH, and blood gases were not altered by rapid defibrination. 5. In view of the similarities between the hemodynamic changes observed after rapid defibrination and acute myocardial ischemia, the role of decreasing fibrinogen concentrations and blood viscosity in aucte myocardial infarction and the sudden death syndrome is questioned.


Combination chemotherapy of biweekly irinotecan (CPT-11) plus tegafur/uracil (UFT) and leucovorin (LV) for patients with metastatic colorectal cancer: phase I/II study in Japanese patients.
We aimed to evaluate the safety and efficacy of combination chemotherapy with biweekly irinotecan (CPT-11) plus oral tegafur/uracil (UFT) and leucovorin (LV) in patients with previously untreated metastatic colorectal adenocarcinoma in phase I/II setting. We recruited 37 patients with histologically proven metastatic colorectal adenocarcinoma. UFT (300 mg/m(2) per day) and LV (75 mg/day) were administered orally on days 1-21. CPT-11 was administered intravenously on day 1 and 15, at an initial dose of 60 mg/m(2), stepping up to 150 mg/m(2) in a traditional phase I fashion. The treatment was repeated every 4 weeks. After patients enrolled into a phase II portion, the efficacy and toxicity of this regimen were also assessed. The recommended dose of CPT-11 was determined to be 150 mg/m(2). Although one patient had a pulmonary embolism after 60 mg/m(2) of CPT-11, the treatment was well tolerated in general. The overall objective response rate was 37.8% (14/37; 95% CI, 22.5-55.2) in all patients. Median progression-free survival was 226 days (95% CI, 133-276). Biweekly CPT-11 plus UFT and LV had a reasonable safety profile with manageable toxicity, and had a promising activity in patients with metastatic colorectal cancer. Further trials are indicated based on the promising results observed in this study.


Therapy service use in children and adolescents with cerebral palsy: An Australian perspective.
The aim of this study was to describe the patterns of therapy service use for a sample of children and adolescents with cerebral palsy over a 1 year period and to identify factors associated with frequency of therapy and parental satisfaction with therapy frequency. Parents of 83 children completed a survey on their child's use of occupational therapy, physiotherapy and speech and language pathology services over the previous year. Participants were randomly selected from a sample stratified by age and Gross Motor Function Classification System (GMFCS) level. During the year prior to survey completion, 83% of children had received occupational therapy, 88% had received physiotherapy and 60% had received speech and language pathology services. Frequency of therapy was higher for younger children (P < 0.01), those classified at GMFCS levels IV-V (P < 0.05) and those attending schools specifically for children with disabilities. Current structures for therapy service delivery for children with cerebral palsy are systems-based, and age-based funding systems and the organisation of services around the education system are preventing the delivery of needs-based therapy. Paediatricians that care for children and young people with cerebral palsy need to pay particular attention to those that may miss out on therapy due to age or school type, and support these families in accessing appropriate therapy.


Reduction of the drug-induced nephrotoxicity by ATP-MgCl2. 1. Effects on the cis-diamminedichloroplatinum-treated isolated perfused kidneys.
cis-Diamminedichloroplatinum (CDDP), a widely used cancer chemotherapeutic agent, has been shown to cause dose-dependent acute renal failure (ARF) probably secondary to a direct nephrotoxic effect on proximal tubule cells. The aim of this study was to determine whether administration of ATP-MgCl2 could ameliorate the deleterious effects of CDDP. Isolated rat kidneys were perfused for 2 hr with a 3.5 g % dextran T-110-Krebs HCO3 solution containing 100 micrograms/ml of CDDP. [3H]Inulin was added to measure GFR. Trace amounts of 14C-methylated cytochrome c (cyt) were added to the perfusate to determine the protein reabsorptive capacity (a sensitive indicator of tubular damage) of isolated perfused rat kidneys. Cyt, inulin radioactivity, and [Na+] were measured in the perfusate and urine in control and CDDP-treated kidneys. In additional experiments, ATP-MgCl2 was added simultaneously (0.3 mM) or 1 hr (2 mM) after CDDP treatment. The results indicate that after 2 hr of perfusion, CDDP treatment led to a marked inhibition of protein reabsorption with only a minimal decrease in Na+ and H2O absorption. Furthermore, GFR was not significantly altered despite a marked diuresis. Post-treatment with ATP-MgCl2 led to partial alleviation of the nephrotoxic effect of CDDP after 1 hr of perfusion. ATP-MgCl2 treatment simultaneously with CDDP, however, fully protected the protein reabsorptive capacity of CDDP-treated kidneys. The potential for administering ATP-MgCl2 simultaneously with CDDP suggests a new therapeutic modality in preventing ARF due to CDDP therapy.


Clinical Trials: Understanding Patient Perspectives and Beliefs About Treatment.
Understanding the experiences of patients with solid tumors who are in phase 1 clinical trials can help nurses to provide optimal care. The purpose of this article is to describe patient perspectives of participating in a phase 1 trial and understanding their disease status and treatment options. In addition, the authors describe the impact of the disease and clinical trial participation on quality of life. 30 patients were interviewed and audio recorded; the interviews were transcribed and content analysis methods were used to identify common themes. Patients reported participating in the phase 1 clinical trial because their doctors informed and encouraged them, they had no other treatment options if they wanted to live longer, or they wanted to help future patients with cancer. Most believed that participation would improve or stabilize their illness and quality of life. They believed that, when the clinical trial ended, there would be new treatments. Participants reported that healthcare providers and family members provided support, and that compassion, cultural awareness, spiritual support, and the need for individual attention were important.


Adaptation variability of Yersinia pseudotuberculosis during long-term persistence in soil.
Adaptation changes in the morphological and biological characteristics of pathogenic Yersinia pseudotuberculosis inhabiting a model soil ecosystem for a long time were studied. Changes in cultural, biochemical, and morphological characteristics of Yersinia and a decrease or loss of virulence were observed under these conditions. The detected changes were phenotypical, i. e. several passages in common nutrient media restored the original characteristics of the strain.


HPTLC-densitometric method for simultaneous determination of salmeterol xinafoate and fluticasone propionate in dry powder inhalers.
A high performance thin layer chromatography (HPTLC) method was developed and validated for determination of two anti-asthmatic drugs, salmeterol xinafoate and fluticasone propionate in co-formulations. Study was performed on pre-coated silica gel HPTLC plates using n-hexane:ethyl acetate:acetic acid (5:10:0.2) as a mobile phase. A TLC scanner set at 250 nm was used for direct evaluation of the chromatograms in reflectance/absorbance mode. Method was validated according to ICH guidelines. Determination coefficients of calibration curves were found 0.9977 and 0.9936 in the ranges 100-1000 and 200-2000 ng band(-1) for salmeterol and fluticasone, respectively. Method had an accuracy of 99.5% for salmeterol and 102.01% for fluticasone. Method had the potential to determine these drugs simultaneously from dosage forms without any interference.


A three step supercritical process to improve the dissolution rate of eflucimibe.
The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.


Influence of data acquisition modes and data analysis approaches on non-targeted analysis of phthalate metabolites in human urine.
Humans are often exposed to phthalates and their alternatives, on account of their widespread use in PVC as plasticizers, which are associated with harmful human effects. While targeted biomonitoring provides quantitative information for exposure assessment, only a small portion of phthalate metabolites has been targeted. This results in a knowledge gap in human exposure to other unknown phthalate compounds and their metabolites. Although the non-targeted analysis (NTA) approach is capable of screening a broad spectrum of chemicals, there is a lack of harmonized workflow in NTA to generate reproducible data within and between different laboratories. The objective of this study was to compare two different NTA data acquisition modes, the data-dependent (DDA) and independent (DIA) acquisition (DDA), as well as two data analysis approaches, based on diagnostic ions and Compound Discoverer software for the prioritization of candidate precursors and identification of unknown compounds in human urine. Liquid chromatography coupled to high-resolution mass spectrometry was used for sample analysis. The combination of three-diagnostic-ion extraction and DDA data acquisition was able to improve data filtering and data analysis for prioritizing phthalate metabolites. With DIA, 25 molecular features were identified in human urine, while 32 molecular features were identified in the same urine samples using DDA data. The number of molecular features identified with level 1 confidence was 11 and 9 using DIA and DDA data, respectively. The study demonstrated that besides sample preparation, the impact of data acquisition must be taken into account when developing a NTA method and a consistent protocol for evaluating such an impact is necessary.


The first case report of dental floss pick-related injury presenting with massive hemoptysis: a case report.
A tracheobronchial foreign body is a rarely mentioned cause of massive hemoptysis. Although an aspirated toothpick is a well-known cause of traumatic injury to the respiratory tract, a similar device called a dental floss pick, which is much larger than a toothpick, has never been described as a tracheobronchial foreign body. We report a case of massive hemoptysis in a 32-year-old man due to a dental floss pick in the left main bronchus. Flexible fiberoptic bronchoscopy was successful in removing the foreign body. Tracheobronchial foreign body can be a medical emergency requiring immediate intervention and massive hemoptysis may be the presenting symptom. Flexible fiberoptic bronchoscopy is recommended as the first-line treatment modality for tracheobronchial foreign body removal. A dental floss pick may present as a tracheobronchial foreign body and can reside in the airway asymptomatically for many years.


Effect of intra-nasal nitrilotriacetic acid trisodium salt in lowering elevated calcium cations and improving olfactory dysfunction in COVID-19 patients.
An association between COVID-19 and olfactory dysfunction has been noted in many patients worldwide. The olfactory adaptation process leads to an increase in intracellular calcium cation levels. Nitrilotriacetic acid trisodium salt has high selective chelation for calcium cations from olfactory mucus. The aim of this work is to test the effect of an intranasal nitrilotriacetic acid trisodium salt to lower the elevated calcium cations in COVID-19 patients with relevant symptoms of olfactory dysfunction. Fifty-eight COVID-19 adult patients with relevant symptoms of olfactory dysfunction were enrolled in a prospective randomized controlled trial. They received a nasal spray containing either 0.9% sodium chloride or 2% nitrilotriacetic acid trisodium salt. Olfactory function was assessed before and after treatment using the Sniffin' Sticks test. Quantitative analysis of calcium cation concentration in nasal secretions was performed using a carbon paste ion-selective electrode. After the application of nitrilotriacetic acid trisodium salt compared to sodium chloride, a significant improvement from functional anosmia to healthy normosmia with significant decrease in calcium cation concentration was observed. Further collaborative research is needed to fully investigate the effect of an intranasal nitrilotriacetic acid trisodium salt in the treatment of olfactory disorders.


Oxidase-mimicking peptide-copper complexes and their applications in sandwich affinity biosensors.
This work reported that the peptide-Cu2+ complexes reveal oxidase-mimicking activities for oxygen reduction and ascorbate oxidation. The peptide features a histidine (His) residue in the first position with respect to the free N-terminal amine. The complexes can be easily integrated with nanomaterials such as gold nanoparticles (AuNPs) to form nanocatalysts or nanozymes, which allows for the fabrication of sensitive sensing platforms. To explore the analytical performances of the peptide-Cu2+ complexes in biosensing, sandwich electrochemical and fluorescent immunoassays of prostate specific antigen (PSA) were performed with AuNP/peptide-Cu2+ conjugates as the nanolabels. In the electrochemical immunoassays, the nanolabels coined as nanocatalysts promoted the electrocatalytic reduction of oxygen. For the fluorescent assays of PSA, the nanolabels coined as nanozymes catalyzed the oxidation of ascorbic acid (AA), and the resulting oxidization product dehydroascorbic acid (DHA) was reacted with o-phenylenediamine (OPD) to form fluorescent 3-(dihydroxyethyl)furo [3,4-b]quinoxaline-1-one (DFQ). The electrochemical and fluorescent signals are proportional to the concentration of PSA in the linear range of 0.001-0.50 and 0.001-2.00 ng/mL, respectively. The low detection limits of the methods (0.40 and 1.00 pg/mL) enabled clinical detection of PSA in serum samples. The findings should be valuable for understanding the biological functions of peptide-Cu2+ complexes, and provide new insight to develop optical and electrochemical sensing platforms for clinical diagnosis.


Apparent sprouting of striatal serotonergic terminals after dopamine-depleting brain lesions in neonatal rats.
Near-total dopamine-depleting brain lesions produced in 3-day-old rats by intracerebroventricular injection of the neurotoxin 6-hydroxydopamine led to pronounced increases in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid contents 1-8 months later. This effect was associated with an increase in in vitro high affinity 5-HT uptake, suggesting that proliferation of new serotonergic terminals had occurred within the striatum. No such effect was obtained when comparable brain lesions were produced in adult rats.


Selective Functionalization of Carbonyl Closo-Decaborate [2-B10H9CO]- with Building Block Properties via Grignard Reagents.
A green, fast and selective approach for the synthesis of mono-substituted closo-decaborate derivatives [2-B10H9COR]2- has been established via a nucleophilic addition reaction between the carbonyl derivative of closo-decaborate [2-B10H9CO]- and the corresponding Grignard reagent RMgX, where R is the ethyl, iso-propyl, pentyl, allyl, vinyl and propynyl groups. This approach is accomplished under mild conditions with 70-80% yields. The significance of these derivative is their ability to constitute building blocks for polymeric integration via the allyl, vinyl and propynyl substituents. All products were characterized by 11B, 1H and 13C NMR, elemental analysis and mass spectrometry.


Serum calprotectin: a potential biomarker to diagnose chronic prosthetic joint infection after total hip or knee arthroplasty.
The preoperative detection of prosthetic joint infection (PJI) prior to revision of total hip or knee arthroplasty is still a challenge. Serum Calprotectin (CP) is a heterodimer of two calcium-binding proteins present in the cytoplasm of neutrophils that is released in inflammatory processes and infections. The objective of this study is to determine the reliability of serum CP in the diagnosis of chronic PJI. 81 patients (40 women, 41 men) that presented a potential indication for revision arthroplasty of the hip (THA; n = 18) or knee (TKA, n = 63) at a single institution were prospectively evaluated. The joints were diagnosed as chronically infected or aseptic based on the musculoskeletal infection society (MSIS) criteria of 2018. Receiver operating characteristics and the Youden's index were used to define an ideal cutoff value. The median serum CP level was significantly higher in the group with chronic PJI (15,120 vs. 4980 ng/ml; p < 0.001) compared to the aseptic cases. The calculated optimal cut-off value was 9910 ng/ml (AUC 0.899, 95% CI 0.830-0.968) with a specificity of 91% and sensitivity of 81%. The present investigation suggests that serum CP has a high specificity and good sensitivity to diagnose chronic PJI after TJA of the knee or hip.


Multidisciplinary approach for the management of complex hepatic injuries AAST-OIS grades IV-V: a prospective study.
Complex hepatic injuries grades IV-V are highly lethal. The objective of this study is to assess the multidisciplinary approach for their management and to evaluate if survival could be improved with this approach. Prospective 54-month study of all patients sustaining hepatic injuries grades IV-V managed operatively at a Level I Trauma Center. survival. univariate and stepwise logistic regression. Seventy-five patients sustained penetrating (47/63%) and blunt (28/37%) injuries. Seven (9%) patients underwent emergency department thoracotomy with a mortality of 100%. Out of the 75 patients, 52 (69%) sustained grade IV, and 23 (31%) grade V. The estimated blood loss was 3,539+/-3,040 ml. The overall survival was 69%, adjusted survival excluding patients requiring emergency department thoracotomy was 76%. Survival stratified to injury grade: grade IV 42/52-81%, grade V 10/23-43%. Mortality grade IV versus V injuries (p < 0.002; RR 2.94; 95% CI 1.52-5.70). Risk factors for mortality: packed red blood cells transfused in operating room (p=0.024), estimated blood loss (p < 0.001), dysryhthmia (p < 0.0001), acidosis (p = 0.051), hypothermia (p = 0.04). The benefit of angiography and angioembolization indicated: 12% mortality (2/17) among those that received it versus a 36% mortality (21/58) among those that did not (p = 0.074; RR 0.32; 95% CI 0.08-1.25). Stepwise logistic regression identified as significant independent predictors of outcome: estimated blood loss (p= 0.0017; RR 1.24; 95% CI 1.08-1.41) and number of packed red blood cells transfused in the operating room (p = 0.0358; RR 1.16; 95% CI 1.01-1.34). The multidisciplinary approach to the management of these severe grades of injuries appears to improve survival in these highly lethal injuries. A prospective multi-institutional study is needed to validate this approach.


Synthesis and anti-HIV-1 activity of 4-[4-(4,6-bisphenylamino-triazin-2-ylamino)-5-methoxy-2-methylphenylazo]-5-hydroxynaphthalene-2,7-disulfonic acid and its derivatives.
A structure-based design approach has been used to optimize a lead HIV-1 entry inhibitor targeted to the envelope glycoprotein gp41. The docking study on this lead compound revealed important structural requirements that need to be preserved as well as structural non-requirements that could be eliminated to substantially reduce the molecular size of the lead compound. Based on the results from docking study, a limited number of analogues were designed and synthesized. This approach yielded a new analogue (compound 4) that retained the anti-HIV-1 activity with reduced molecular size approaching towards more drug-like character.


Impact of green technological innovations on environmental quality for Turkey: evidence from the novel dynamic ARDL simulation model.
The contribution of this research is to provide empirical evidence that investing in green technology innovation (GTI) can reduce the ecological footprint in Turkey, which can lead to sustainable economic growth and environmental quality. The research also highlights the importance of controlling energy consumption, GDP, trade openness, and urbanization, as these variables have a positive or negative effect on ecological footprint. The findings of this research can be useful for the Turkish government, policymakers, and environmentalists to promote the implementation of GTI and eco-friendly resources, which can reduce the impact of climate change and contribute to economic prosperity. Overall, this research provides important information for decision-makers to adopt policies that prioritize green innovation and environmental protection in Turkey.


One-year post-discharge resource utilization and treatment patterns of patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with ticagrelor or prasugrel.
Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel. Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences. Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month; P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month; P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 %; P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 %; P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month; P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month; P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 %; P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days; P = 0.002), with no significant difference in mean adherence (61 vs. 63 %; P = 0.17). Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations.


Refining the tree of lifeLife as We Made It: How 50,000 Years of Human Innovation Refined-and Redefined-Nature Beth Shapiro Basic Books, 2021. 352 pp.
Human interventions, both intentional and unintentional, define a new chapter in Earth's storied history.


Hypertension in kidney transplantation.
Arterial hypertension in renal transplant patients plays a major role in the progression to chronic allograft failure, and in morbidity and mortality associated with cardiovascular disease. Its cause is diverse, with contributions not only from donor and/or recipient factors, but it also is influenced strongly by the type of immunosuppressive regimen. Despite increased awareness of the adverse effects of hypertension in both graft and patient survival, long-term studies have shown that arterial hypertension in the transplant population has not been controlled adequately. Ambulatory blood pressure measurements provide the advantage of a better assessment of the diurnal blood pressure variation, a predictor of target organ damage and cardiovascular morbidity and mortality events. Although the available data do not support the recommendation of any class of antihypertensive medication as preferred agents for blood pressure management in the transplant population, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers have shown beneficial effects beyond their antihypertensive effects. Clinical data in transplant recipients are emerging that suggest that applying interventions proven to be effective in reducing cardiovascular morbidity and mortality in the general population may be effective for the transplant population.


Data acquisition and analysis of pulsatile signals using a personal computer: an application in cardiovascular physiology.
Software is described which collects and analyzes pulsatile analog signals using an APPLE PC and a modestly priced analog-digital interface. The program will input and output data, store and retrieve data to disk and display data on the monitor. Four types of data analysis determine mean, maximum and minimum values and frequency in various combinations. For example, the present program analyzes cardiovascular signals for heart rate, stroke volume, cardiac output, systolic, diastolic and mean pressures over a representative 10 s period. Simple modifications to the program are described which extend its range of application.


Castleman's disease: an unusual retroperitoneal mass.
Castleman's disease (angiofollicular lymph node hyperplasia) rarely presents as an isolated retroperitoneal mass radiographically indistinguishable from retroperitoneal malignancies. We report a case of the hyaline vascular variant of Castleman's disease presenting as a calcified pararenal mass. Computerized tomography and nuclear magnetic resonance imaging of this lesion are presented, and its clinical behavior and management are discussed.


A Brodie's Abscess of Femoral Neck Mimicking Osteoid Osteoma: Diagnostic Approach and Management Strategy.
Brodie's abscess usually presents as a diagnostic dilemma resulting in a diagnostic delay. It mimics various benign and malignant conditions both clinically and radiologically. This report describes a case of a 14 year old boy who presented with a clinical and radiological picture of osteoid osteoma of proximal femur but found to have a brodie's abscess on histology and culture. It describes the clinical spectrum of subacute osteomyelitis, its unusual MRI features and the importance of obtaining a histological diagnosis before definitive treatment.


Evidence-based medicine audit as a tool for improving emergency ophthalmology.
To audit the proportion of interventions in emergency ophthalmology that are evidence based and to determine whether the quality of care can be improved. Audit of diagnosis-intervention pairs was carried out retrospectively in March 2003. The outcomes were assessed for evidence level reached in the Medline database 1966-2003 and the Cochrane Database of Systematic Reviews. Locally agreed guidelines were issued and the study repeated prospectively in March 2004, when new medical staff were at a similar level of experience. The participants had no prior knowledge of the study to avoid prescribing bias (Hawthorne's phenomenon). In the first part of the audit in 2003, 71% of interventions were evidence based, with 36% derived from systematic reviews, meta-analysis or randomised controlled trials (evidence levels 1-3). After guidelines for care were implemented in 2004, there was an improvement in the number of evidence-based interventions to 82% (P=0.04), and levels 1-3 were reached in 60% (P=0.02). The proportion with no evidence or against evidence dropped from 29 to 18% (P=0.04). An additional benefit was to reduce the number of re-attendances required. Evidence-based medicine can be used to improve the quality of care in the acute ophthalmic setting, both in refining the standard of interventions and in reducing the number of hospital visits.


Incidence and predictors of major hemorrhagic complications from thrombolytic therapy in patients with massive pulmonary embolism.
The risk factors for bleeding in patients receiving recombinant tissue-type plasminogen activator for massive pulmonary embolism are not known. The hospital records of 132 consecutive patients who received recombinant tissue-type plasminogen activator for massive pulmonary embolism were retrospectively reviewed. Bleeding was estimated by using the bleeding severity index, a method previously validated in patients receiving anticoagulants. Multivariate stepwise logistic regression was used to identify independent risk factors for bleeding. Four other definitions of bleeding in large pulmonary embolism thrombolytic trials were also used, and the agreement among these criteria was assessed. According to the bleeding severity index, 33 patients (25%) had one or more major bleeding complications. Hemorrhage at the venous puncture site for angiography was the most frequent complication (15 patients, 11%). Major bleeding at the catheterization site was more common at the femoral site (14 of 63 patients = 22%) than at the brachial site (1 of 63 patients = 2%; P = 0.0004). The use of the five different bleeding definitions resulted in a variation in the major bleeding rate from 3% to 43%. The kappa coefficient varied from 0.07 to 0.84, indicating poor agreement between most of the classifications. The use of the femoral vein for pulmonary angiography was the only variable significantly associated with major bleeding. Most of the differences observed in the pulmonary embolism thrombolytic trials are likely related to the differences in the definition of bleeding rather than to the thrombolytic regimen.


Disturbances of the menstrual cycle in bulimia nervosa.
Blood was obtained three times a week throughout one menstrual cycle or during a 6-week period from 15 patients with bulimia nervosa and from 10 healthy age-matched controls. Of the patients, three had amenorrhoea, eight had oligomenorrhoea and four had regular cycles. Normal follicular development, as judged from continuously low oestradiol (E2) values (less than 120 pg/ml or less than 440 pmol/l), did not occur in seven patients. Compared to patients with increasing E2 values (greater than 120 pg/ml), these seven had a significantly lower body weight. Among the eight patients showing follicular development (E2 greater than 120 pg/ml), four reported regular cycles, but only three developed normal plasma progesterone (P4) values during the luteal phase (P4 greater than 3 ng/ml or greater than 9.5 nmol/l). The luteal phase was of normal length in only one bulimic patient.


Rectovaginal fistula after Posterior Intravaginal Slingplasty and polypropylene mesh augmented rectocele repair.
Posterior Intravaginal Slingplasty and mesh augmented rectocele repairs are procedures promoted for correction of vaginal relaxation. There is little data on the complications of these procedures alone or in combination. The first report of rectovaginal fistula after Posterior Intravaginal Slingplasty with graft augmented rectocele repair is presented. A 60-year-old female developed a rectovaginal fistula 3 months after undergoing a Posterior Intravaginal Slingplasty and mesh augmented rectocele repair for prolapse. Two attempts at correcting the fistula failed and there was a recurrence of her vault prolapse. She may now require diverting colostomy and repeat repair of her vault prolapse. The case report highlights the difficulties in treating a rectovaginal fistula that developed after Posterior Intravaginal Slingplasty and mesh augmented rectocele repair for vaginal vault prolapse. More data regarding complications associated with use of these procedures is needed prior to widespread use.


P-selectin mediates leukocyte rolling in concanavalin-A-induced hepatitis.
Concanavalin-A (Con-A)-induced hepatitis is an experimental model of human autoimmune hepatitis characterized by leukocyte activation and infiltration of the liver. The aim of the present study was to evaluate the role of P-selectin on leukocyte-endothelial interactions within the hepatic microvasculature in response to Con-A. The study was performed in P-selectin-deficient mice and wild-type mice pretreated with anti-P-selectin blocking monoclonal antibody (mAb) or vehicle. After 2 h of Con-A (20 mg/kg i.v.) or PBS administration, leukocyte rolling and adhesion and the index of sinusoidal perfusion were evaluated using the intravital microscopy technique in the liver. Apoptosis was determined by flow cytometry analysis of caspase-3 activity assayed on freshly isolated hepatocytes. Con-A induced a significant increase in leukocyte rolling, mainly located at the central venule (2.1+/-0.4 vs 0.6+/-0.2 cells/min in wild-type mice treated with vehicle) and less marked, but still significant, in portal venules. This was associated with a significant increase in leukocyte adhesion. In P-selectin-deficient mice treated with Con-A, leukocyte rolling in portal and central venules was markedly reduced. However, leukocyte adhesion was only partially attenuated. A few sinusoids were perfused in wild-type mice treated with Con-A (26%). The percentage of perfused sinusoids was significantly higher in P-selectin-deficient mice (45%; P<0.05 vs wild-type). Similar effects were noted after the simultaneous injection of Con-A and anti-P-selecting mAb in wild-type mice. After Con-A treatment, apoptosis was markedly reduced in isolated hepatocytes of P-selectin-deficent mice (37+/-7% vs 75+/-5% in wild type). The results of this intravital microscopy study clearly demonstrate that P-selectin is involved in the initial leukocyte rolling that leads to the development of Con-A-induced liver injury.


Electromyographic activity of sternocleidomastoid muscle in patients with Parkinson's disease.
The aim of this study was to evaluate the effect of administration of levo-dopa, which means without effect-off state and under effect-on state, on the sternocleidomastoid muscle electromyographic activity (SCM-EA) in patients with Parkinson's disease (PD) at rest and to compare it to asymptomatic subjects. Ten patients with PD, mean age 64.6+/-6.2 (SD) years and nine asymptomatic subjects, mean age 61.4+/-5.9 (SD) years were studied. The SCM-EA was evaluated during maximal inspiratory pressure and breathing at rest through surface electromyography. Statistical analysis was performed with t-test (anthropometric data and SCM-EA of patients in off state to asymptomatic), Mann-Whitney (SCM-EA of patients in on state to asymptomatic) and Wilcoxon test (SCM-EA off and on states). The effect size index (d) was calculated for statistically significant differences. There were no significant differences in SCM electromyographic activity between patients with PD comparing off to on (p=0.13) or among on state to asymptomatic subjects (p=0.06). However, when subjects with PD in off where compared to asymptomatic there was a significantly higher SCM electromyographic activity (p=0.03, d=1.09). These patients, without levo-dopa effect, when compared with asymptomatic subjects, present a significantly higher electromyographic activity of SCM, the main accessory respiratory muscle, which could be related to an increased work of breathing.


Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [(18)F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience.
Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI. FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p < 0.001). FET and BV positivity were in agreement in only 26 of the 32 patients and in 42 of 63 lesions, and spatial congruence in the tumour volumes as assessed by the Dice coefficients was generally poor with median Dice coefficients exceeding 0.1 in less than half the patients positive on at least one modality for any pair of modalities. In 56 % of the patients susceptibility artefacts in DSC BV maps overlapped the tumour on MRI. The study demonstrated that although tumour volumes determined by BV MRI and FET PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials.


[Pathogenetic therapy of nervous system and muscular diseases using large doses of prednisolone on alternate days].
A total of 230 patients with myasthenia, polymositis, disseminated sclerosis and myeloradiculopolyneuronitis were administered high doses of prednisolone (up to 100 mg) every other day. The treatment efficacy and low incidence of side effects and complications are emphasized. High doses of prednisolone given every other day do not inhibit secretions of endogenic ACTH and cortisol. The immunodepressant effect of the drug remains unchanged.


In the shadow of phylogenetic uncertainty: the recent diversification of Lysandra butterflies through chromosomal change.
The phylogeny of the butterfly genus Lysandra (Lycaenidae, Polyommatinae) has been intractable using both molecular and morphological characters, which could be a result of speciation due to karyotype instability. Here we reconstruct the phylogeny of the group using multi-locus coalescent-based methods on seven independent genetic markers. While the genus is ca. 4.9 Mya old, the diversification of the extant lineages was extremely recent (ca. 1.5 Mya) and involved multiple chromosomal rearrangements. We find that relationships are uncertain due to both incomplete lineage sorting and hybridization. Minimizing the impact of reticulation in inferring the species tree by testing for mitochondrial introgression events yields a partially resolved tree with three main supported clades: L. punctifera+L. bellargus, the corydonius taxa, and L. coridon+the Iberian taxa, plus three independent lineages without apparently close relatives (L. ossmar, L. syriaca and L. dezina). Based on these results and new karyotypic data, we propose a rearrangement recognizing ten species within the genus. Finally, we hypothesize that chromosomal instability may have played a crucial role in the Lysandra recent diversification. New chromosome rearrangements might be fixed in populations after severe bottlenecks, which at the same time might promote rapid sorting of neutral molecular markers. We argue that population bottlenecks might be a prerequisite for chromosomal speciation in this group.


Patient Perspectives on Active vs. Passive Music Therapy for Cancer in the Inpatient Setting: A Qualitative Analysis.
Music therapy (MT) is a nonpharmacologic therapy where licensed therapists provide active (e.g., singing, playing songs) or passive (e.g., listening) music-based interventions. Both active and passive MT are effective techniques for treating cancer-related symptoms. However, the influence of active vs. passive MT techniques on patient-reported perceptions and experiences of care have yet to be explored. To understand how active and passive MT is perceived and experienced by patients with cancer. We conducted a retrospective analysis of semistructured interviews collected as part of a quality improvement study (n = 20) with patients in the inpatient setting who had received active or passive MT within the past 24 hours. Transcripts were analyzed using thematic content analysis. Four themes emerged: 1) Different articulations of benefit for recipients of active vs. passive MT; 2) patient choice as a form of empowerment; 3) changed perception of hospital experience; and 4) differing recommendations for future MT. Recipients of active MT emphasized the session's interactive elements, finding the sessions stimulating by providing opportunities for joyous social interaction not centered on their diagnosis. Passive MT recipients focused on the calming therapeutic effect of the session, easing anxieties through focus and reflection on the music itself. This analysis builds on current MT literature by providing insights specifically from oncology patients treated in the inpatient setting. Patients experience active and passive MT in different ways and perceived unique benefits for coping with cancer from each technique. Our findings can inform development of specific MT for symptom control in hospital settings.


Centralizing the Cemented Exeter Femoral Stem Using the Direct Lateral Approach: Surgical Tips and Radiological Evaluation.
Varus malalignment in total hip arthroplasty has been associated with poor long-term outcomes and complications including abnormal load distribution, endosteal osteolysis, frank loosening, and periprosthetic fractures. Postoperative radiographic assessment was performed on 224 patients from our case series who underwent cemented Exeter total hip arthroplasty using the direct lateral approach alone. No patient had a true varus-aligned stem (ie, ≤-5° on the coronal assessment). We describe our surgical technique, with 4 easily reproducible technical tips to achieve positional consistency of the femoral stem: commencing stem insertion from the piriform fossa entry point, using a femoral stem distal centralizer, aiming the tip of the component to the center of the patella, and placing the thumb between the calcar and inferior neck of the femoral component to prevent the stem from tipping into varus.


No-touch isolation techniques for pancreatic cancer.
The rate of recurrence, including liver metastasis is high in pancreatic cancer, even when complete surgical resection is performed as a curative treatment. In patients with pancreatic cancer, the handling and grasping of the pancreas during surgery may increase the risk of liver metastasis, as squeezing may spread cancer cells via the portal vein. A no-touch isolation technique might prevent the spread of cancer cells via the hematogenous metastatic route in patients with pancreatic cancer. However, while no-touch isolation techniques are simple, feasible and, in theory, ideal procedures for the surgical treatment of pancreatic cancer, there have been no randomized controlled prospective studies to validate their advantages and their efficacy remains controversial. It is, therefore, worth investigating the use of no-touch isolation techniques in pancreatic cancer.


The polyisoprenoid chain length influences the interaction of ubiquinones with phospholipid bilayers.
The interaction between ubiquinone homologues with polyisoprenoid chain lengths varying from 3 to 10 units and dipalmitoylphosphatidylcholine bilayers has been examined by differential scanning calorimetry and wide angle X-ray diffraction analysis. Decreasing the polyisoprenoid chain lengths of ubiquinone in mixed dispersions with phospholipid in mol ratios of about 10 mol% caused a decrease in the gel-liquid crystalline phase transition temperature of the phospholipid and a broadening of the transition. Enthalpy measurements showed that most of the phospholipid (greater than 92%) was involved in the transition endotherm and the formation of a gel phase was also confirmed by the presence of a sharp X-ray reflection of 0.42 nm. These results are consistent with a model in which all of the ubiquinone homologous ultimately undergo a phase separation from phospholipid molecules entering a gel phase on cooling below the phase transition temperature. Reducing the length of the polyisoprenoid chain alters the amphipathic balance of the ubiquinone molecules and is reflected in the tendency of shorter chain ubiquinones to intercalate between the phospholipid molecules upon reheating through the main phase transition.


Learning by observation in the macaque monkey under high experimental constraints.
While neuroscience research has tremendously advanced our knowledge about the neural mechanisms of individual learning, i.e. through trial-and-error, it is only recently that neuroscientists have begun to study observational learning, and thus little is known about its neural mechanisms. One limitation is that observational learning has been addressed under unconstrained experimental conditions, not compatible with neuronal recordings. This study examined observational learning in macaque monkeys under the constraining conditions of behavioral neurophysiology. Two animals sat in primate chairs facing each other, with their head fixed. A touch screen was placed face up between the chairs at arm's reach, and the monkeys were trained on an abstract visuomotor associative task. In one experiment, the monkeys alternated the roles of "actor" and "observer". The actor learned to associate visual cues with reaching targets, while the observer "watched" freely. Then, the observer was given the same cue-target associations just performed by the actor, or had to learn new, not previously observed ones. The results show that learning performance is better after observation. In experiment 2, one monkey learned from a human actor who performed the task with errors only, or with successes only in separate blocks. The monkey's gain in performance was higher after observation of errors than after successes. The findings suggest that observational learning can occur even under highly constraining conditions, and open the way for investigating the neuronal correlates of social learning using the methods of behavioral neurophysiology.


Anti-neuroinflammation ameliorates systemic inflammation-induced mitochondrial DNA impairment in the nucleus of the solitary tract and cardiovascular reflex dysfunction.
Decreased heart rate variability (HRV) leads to cardiovascular diseases and increased mortality in clinical studies. However, the underlying mechanisms are still inconclusive. Systemic inflammation-induced neuroinflammation is known to impair the autonomic center of cardiovascular regulation. The dynamic stability of blood pressure and heart rate (HR) is regulated by modulation of the reciprocal responses of sympathetic and parasympathetic tone by the baroreflex, which is controlled by the nucleus of the solitary tract (NTS). Systemic inflammation was induced by E. coli lipopolysaccharide (LPS, 1.2 mg/kg/day, 7 days) peritoneal infusion via an osmotic minipump in normotensive Sprague-Dawley rats. Systolic blood pressure (SBP) and HR were measured by femoral artery cannulation and recorded on a polygraph under anesthesia. The low-frequency (LF; 0.25-0.8 Hz) and high-frequency (HF; 0.8-2.4 Hz) components of SBP were adopted as the indices for sympathetic vasomotor tone and parasympathetic vasomotor tone, while the baroreflex effectiveness index (BEI) was adopted from the analysis of SBP and pulse interval (PI). The plasma levels of proinflammatory cytokines and mitochondrial DNA (mtDNA) oxidative damage were analyzed by ELISA. Protein expression was evaluated by Western blot. The distribution of oxidative mtDNA was probed by immunofluorescence. Pharmacological agents were delivered via infusion into the cisterna magna with an osmotic minipump. The suppression of baroreflex sensitivity was concurrent with increased SBP and decreased HR. Neuroinflammatory factors, including TNF-α, CD11b, and Iba-1, were detected in the NTS of the LPS group. Moreover, indices of mtDNA damage, including 8-OHdG and γ-H2AX, were significantly increased in neuronal mitochondria. Pentoxifylline or minocycline intracisternal (IC) infusion effectively prevented mtDNA damage, suggesting that cytokine and microglial activation contributed to mtDNA damage. Synchronically, baroreflex sensitivity was effectively protected, and the elevated blood pressure was significantly relieved. In addition, the mtDNA repair mechanism was significantly enhanced by pentoxifylline or minocycline. These results suggest that neuronal mtDNA damage in the NTS induced by neuroinflammation could be the core factor in deteriorating baroreflex desensitization and subsequent cardiovascular dysfunction. Therefore, the enhancement of base excision repair (BER) signaling in mitochondria could be a potential therapeutic strategy for cardiovascular reflex dysregulation.


Tranilast, an anti-allergic drug, possesses antagonistic potency to angiotensin II.
N-(3',4'-dimethoxycinnamoyl) anthranilic acid (tranilast), an effective anti-allergic drug, has successfully prevented restenosis in patients who have undergone percutaneous transluminal coronary angioplasty. To elucidate the mechanism of tranilast, we investigated its antagonistic effect to angiotensin II, which plays a pivotal role in the proliferation of vascular smooth muscle cells, using angiotensin II-induced contractions in human gastroepiploic artery and rabbit aorta. The possible antagonistic effects of other anti-allergic agents such as 4-( p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthal azinone hydrochloride (azelastine), 9-methyl-3-( 1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyramidin-4-one potassium salt (pemirolast) and disodium cromoglycate were also compared. Tranilast dose-dependently inhibited the angiotensin II-induced contractions in human and rabbit arteries (IC50 = 3.6x10(-5) M and pD'2 = 3.69, respectively). Pemirolast showed a weak antagonistic effect to angiotensin II, but the effective concentration cannot be administered in clinical dosage. Tranilast and pemirolast had no effect on the concentration-contractile response curves for KCI and norepinephrine. Azelastine inhibited angiotensin II-, KCl- and norepinephrine-induced contractions non-specifically, while disodium cromoglycate did not affect these contractile responses. Tranilast but not azelastine showed synergistic action with 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimi dazole-7-carboxylic acid (CV- 11974) in antagonizing angiotensin II-induced contraction and the inhibitory pattern was similar to that of the non-peptide angiotensin II AT1 receptor antagonist CV-11974. These findings indicate that only tranilast possesses the unique ability to antagonize angiotensin II in clinical dosage, which may contribute at least in part to prevention of restenosis after percutaneous transluminal coronary angioplasty.


Naphthalene biodegradation in temperate and arctic marine microcosms.
Naphthalene, the smallest polycyclic aromatic hydrocarbon (PAH), is found in abundance in crude oil, its major source in marine environments. PAH removal occurs via biodegradation, a key process determining their fate in the sea. Adequate estimation of PAH biodegradation rates is essential for environmental risk assessment and response planning using numerical models such as the oil spill contingency and response (OSCAR) model. Using naphthalene as a model compound, biodegradation rate, temperature response and bacterial community composition of seawaters from two climatically different areas (North Sea and Arctic Ocean) were studied and compared. Naphthalene degradation was followed by measuring oxygen consumption in closed bottles using the OxiTop(®) system. Microbial communities of untreated and naphthalene exposed samples were analysed by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) and pyrosequencing. Three times higher naphthalene degradation rate coefficients were observed in arctic seawater samples compared to temperate, at all incubation temperatures. Rate coefficients at in situ temperatures were however, similar (0.048 day(-1) for temperate and 0.068 day(-1) for arctic). Naphthalene biodegradation rates decreased with similar Q10 ratios (3.3 and 3.5) in both seawaters. Using the temperature compensation method implemented in the OSCAR model, Q10 = 2, biodegradation in arctic seawater was underestimated when calculated from the measured temperate k1 value, showing that temperature difference alone could not predict biodegradation rates adequately. Temperate and arctic untreated seawater communities were different as revealed by pyrosequencing. Geographic origin of seawater affected the community composition of exposed samples.


Effect of postoperative pain treatment on outcome-current status and future strategies.
The effect of postoperative pain relief on morbidity and hospital stay is reviewed. Beneficial effects of postoperative pain relief by patient-controlled analgesia (PCA) opioids on morbidity and hospital stay have not been documented. The clinical outcome effects of the 20%-30% opioid sparing by non-steroidal anti-inflammatory agents have not been defined, but recent data suggest hastened recovery in cholecystectomy and knee surgery. The effect of continuous epidural analgesia on morbidity and hospital stay remains controversial except for improved pulmonary outcome. However, existing randomised trials on continuous epidural analgesia have insufficient design due to predominantly opioid-based epidural analgesia and the lack of a revision of perioperative care programmes to take advantage of the beneficial physiological effects of balanced epidural analgesia. The effects of pain relief on outcome remains debatable, despite beneficial effects of pathophysiological responses. Future outcome studies are required where optimised dynamic pain relief is integrated with a multimodal rehabilitation programme.


Exploring the Notion of Context in Medical Data.
Scientific and technological knowledge and skills are becoming crucial for most data analysis activities. Two rather distinct, but at the same time collaborating, domains are the ones of computer science and medicine; the former offers significant aid towards a more efficient understanding of the latter's research trends. Still, the process of meaningfully analyzing and understanding medical information and data is a tedious one, bound to several challenges. One of them is the efficient utilization of contextual information in the process leading to optimized, context-aware data analysis results. Nowadays, researchers are provided with tools and opportunities to analytically study medical data, but at the same time significant and rather complex computational challenges are yet to be tackled, among others due to the humanistic nature and increased rate of new content and information production imposed by related hardware and applications. So, the ultimate goal of this position paper is to provide interested parties an overview of major contextual information types to be identified within the medical data processing framework.


Retinal Hydration Assessment With Optical Coherence Tomography: Unraveling Its Significance in Retinal Fluid Dynamics, Macular Edema and Cell Viability.
The purpose of this study was to quantify retinal hydration (RH) levels with optical coherence tomography (OCT) and determine the extent of cellular damage resulting from intraretinal fluid alterations. We took 6.0 mm sections of the human sensory retina that were excised from 18 fresh (<24 hours) donor eyes. They were either exposed to various osmotic stresses between 90 and 305 mOsm or dehydrated under a laminar flow hood. Change in tissue weight was used to calculate the retinal water content (RWC). Image analyses were conducted on OCT between 0 and 180 minutes to assess retinal thickness (RT) and "optically empty areas" (OEAs) representing intraretinal fluid. Correlations were sought among RWC, OEA, RWC, and RT. The effect of RH on retinal cell viability (RCV) was assessed with the Live-Dead Assay. RH demonstrated a stronger correlation with the OEA than plain RT measurements (r = 0.99, P < 0.001). RH-RCV interaction fits well to a bell-shaped curve. A significant proportion of retinal cells (>80%) remained viable despite the change in RH ranging between 0.87 and 1.42 times. This "safe zone" was found to be associated with a 22% increase in OEA (r = 0.99, P < 0.01). OCT has been demonstrated as a valuable tool for assessing RH and can be used for intraretinal fluid content analysis. RH is a better indicator of RCV compared with RT. Computing RH may improve the determination of functional outcome of intravitreal pharmacotherapeutics used for diabetic macular edema and exudative age-related macular degeneration. We link basic research and clinical care by assessing retinal hydration's impact on retinal fluid dynamics, macular edema, and cell viability.


High-gain printed monopole antenna with dual-band characteristics using FSS-loading and top-hat structure.
In this paper, a printed monopole antenna with high-gain and dual-band characteristics for applications in wireless local area networks and the internet of things sensor networks is presented. The proposed antenna consists of a rectangular patch with multiple matching stubs surrounded to improve the impedance bandwidth of the antenna. The antenna incorporates a cross-plate structure which is seated at the base of the monopole antenna. The cross-plate consist of metallic plates aligned perpendicularly which enhances the radiations from the edges of the planar monopole to maintain uniform omnidirectional radiation patterns within the antenna's operating band. Furthermore, a layer of frequency selective surface (FSS) unit cells and a top-hat structure is added to the antenna design. The FSS layer consist of three unit cells printed at the back side of the antenna. The top-hat structure is placed on top of the monopole antenna and comprises of three planar metallic structures arranged in a hat-like configuration. The coupling of both the FSS layer and the top-hat structure presents a large aperture to increase the directivity of the monopole antenna. Thus, the proposed antenna structure realizes a high gain without compromising the omnidirectional radiation patterns within the antenna's operating band. A prototype of the proposed antenna is fabricated where good agreement is achieved between the measured and full-wave simulation results. The antenna achieves an impedance bandwidth |S11| < - 10 dB and VSWR ≤ 2 for the L and S band at 1.6-2.1 GHz and 2.4-2.85 GHz, respectively. Furthermore, a radiation efficiency of 94.2% and 89.7% is realized at 1.7 and 2.5 GHz, respectively. The proposed antenna attains a measured average gain of 5.2 dBi and 6.1 dBi at the L and S band, respectively.


Risk of Parkinson's Disease in Celiac Disease: A Swedish Population-Based Study.
Using a population-based matched cohort design, we assessed the association of celiac disease (CeD) with risk of PD by comparing patients with biopsy-confirmed CeD in Sweden to a biopsy-free population and their unaffected siblings, separately. No overall association was observed but CeD diagnosed before age 60 associated positively with incident diagnosis of PD (hazard ratio [HR] = 1.29; 95% confidence interval [CI]: 1.02-1.62), which was mainly attributed to the significantly elevated risk detected after 10-15 years since biopsy (HR = 1.68; 95% CI: 1.05-2.68). Our findings imply an increased vulnerability to long-term PD development among patients with CeD diagnosed before 60s. ANN NEUROL 2023;94:911-916.


Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hürthle cell and/or apocrine-like changes.
We have recently observed that Hürthle cell tumours and papillary thyroid carcinoma with tumour cells showing decapitation of luminal portion of the cytoplasm (apocrine-like changes) display negative or decreased immunoreactivity for HBME. The purpose of this study is to correlate papillary thyroid carcinoma with positive and negative immunoreactivity for HBME with the histopathological features. Two hundred and five thyroid neoplasms including carcinoma and adenomas were grouped into Hürthle cell tumours, tumours with or without some features of Hürthle cells, tumours with apocrine-like changes and adenomas with or without limited nuclear features of papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma. All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma that have areas of limited nuclear features but not diagnostic for papillary thyroid carcinoma showed stronger immunostaining for HBME than their respective counterparts with Hürthle cell changes. All Hürthle cell tumours showed negative to focal reactivity. This decrease of reactivity for HBME was proportional to the levels of Hürthle cell changes. In addition, focal to extensive apocrine-like changes were seen in most Hürthle cell neoplasms and rarely seen in non-Hürthle cell neoplasms. Apocrine-like changes abolished or decreased HBME immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear features. Immunostaining for cytokeratin AE3 was not affected by Hürthle cell or apocrine-like changes. All papillary thyroid carcinomas without Hürthle cell or apocrine-like differentiation are reactive for HBME. Hürthle cell tumours and tumours with Hürthle cell or apocrine-like changes show negative or focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker for papillary thyroid carcinoma and tumours with limited nuclear features.


Erratum: Survey of supraglottic airway devices usage in anaesthetic practice in South Indian State: Erratum.
[This corrects the article on p. 190 in vol. 59, PMID: 25838594.].


Sense it and use it: interoceptive accuracy and sensibility in suicide ideators.
Interoceptive deficits have been found to be associated with suicidal ideation and behavior. However, an objective measure of interoceptive accuracy has not been investigated in participants with suicide ideation, by now. This study aimed at investigating interoceptive accuracy and sensibility in persons with and without suicide ideation (SI) while controlling for severity of depressive symptoms. Ninety-five participants (age: M = 34.8, SD = 11.6, n = 56 female [58.9%]; n = 51 patients with a Major Depressive Disorder and n = 44 healthy participants) were assessed for interoceptive accuracy and sensibility, depression and SI. Twenty-five participants (26%) reported SI. They showed interoceptive accuracy comparable to persons without SI (t = -.81, p = .422), but significantly lower interoceptive sensibility. After controlling for severity of depressive symptoms in a hierarchical linear regression analysis, most associations between interoceptive sensibility and SI disappeared. Results suggest that suicide ideators do not lack the ability to perceive their own bodily signals but they feel less able to use them in a way that is advantageous for them. Differences between suicide ideators and non-ideators appear to be largely driven by depressive symptoms (depression bias).


Natural djurleite with refined composition Cu61.39S32 revealing disorder of some Cu sites.
A djurleite crystal was discovered from a natural sample originally labelled as chalcocite. The djurleite crystal under investigation has a refined composition of Cu61.39S32, thus revealing a Cu deficiency compared to the originally reported Cu62S32 phase [Evans (1979). Z. Kristallogr. 150, 299-320], where all atomic sites are reported to be fully occupied. In addition, the current refinement revealed a splitting of eight of the Cu sites into pairs.


Conditioning lesion effects on rat sciatic nerve regeneration are influenced by electrical stimulation delivered to denervated muscles.
The rate of regeneration and the initial delay of the fastest growing fibers of the rat sciatic nerve were electrophysiologically evaluated after a freeze at mid-thigh. A prior section or a prior freeze at the ankle level increased the rate of regeneration and decreased the initial delay with different magnitudes. These phenomena are named 'conditioning lesion effects'. A daily electrical stimulation transcutaneously delivered to the foot sole muscles from the day following their denervation by the prior lesion did not modify the increased rate of regeneration but prevented the decrease of the initial delay whatever the type of the prior lesion. Therefore, the initiation of earlier sprouting of the parent axons seems to be specifically controlled by a signal associated with muscle denervation properties.