Intravenous administration of the endothelin-1 antagonist BQ-123 does not ameliorate myocardial ischaemic injury following acute coronary artery occlusion in the dog.
It has been proposed that myocardial ischaemic injury is modulated in part by the release of endothelin-1 from the coronary endothelium either during ischaemia or following reperfusion. Release of sufficient amounts of endothelin-1 would result in coronary vasoconstriction and could potentiate ischaemic damage. An endothelin-1 antagonist, BQ-123, was given intravenously to evaluate the role of endothelin-1 in postischaemic injury and determine whether blockade of the ETA receptor would afford protection from ischaemia/reperfusion injury. Myocardial injury was induced in anaesthetised dogs using 90 min of left circumflex coronary artery occlusion followed by 4 h of reperfusion. Animals treated with a continuous intravenous infusion of BQ-123 (0.1 mg.kg-1.min-1), begun 10 min before ischaemia and continued throughout ischaemia and reperfusion, were compared to saline treated animals. After 4 h of reperfusion the myocardial infarct size measured by triphenyltetrazolium chloride staining was not different between the two groups. Infarct size in the control group was 25.7 (SEM 5.4)% of the area at risk while BQ-123 treatment resulted in an infarct size of 29.2(7.1)% of the area at risk (p = 0.70). Plasma endothelin-1 concentration measured at the coronary sinus was only significantly increased following 5 min of reperfusion. The intravenous administration of a specific ETA receptor antagonist does not protect against ischaemia/reperfusion injury. These results suggest that endothelin-1 receptor antagonists require access to the area at risk during occlusion to protect the myocardium from ischaemic injury.


Assessment of the main pancreatic duct using computed tomography with multiplanar reconstructions.
The aim of this study was to assess the morphology of the main pancreatic duct (MPD) using multiplanar reconstructions and to compare this with the morphology of the MPD of anatomic subjects. The morphology of the MPD was studied by means of multiplanar reconstructions obtained on the one hand from thin tomodensitometric slices and on the other hand from the dissection of anatomic subjects. This study involved 15 subjects in each group. Full multiplanar reconstruction was obtained in 13 cases. In 2 cases, the isthmus did not appear in the reconstructions. The morphology of the MPD was similar in both groups. The length of the MPD was identical at the head and isthmus of the pancreas in both groups but was greater in the dissection group than in the reconstruction group in the body and tail areas of the pancreas. The diameter of the MPD was greater at the head of the pancreas in the dissection group and was identical in both groups for the other segments of the MPD. Multiplanar tomodensitometric reconstruction of the main pancreatic duct is feasible. This new technique, currently under evaluation, could allow the study of canalar pathologies of the pancreas through tomodensitometry.


[Electron microscopic study on calcification of porous hydroxyapatite ceramics implanted in the submandibular glands of rats].
This study was primarily designed to determine the tissue responses and the initial calcification profiles after the implantation of porous hydroxyapatite ceramics (HAP), and secondly, to find out the effects of chronic isoproterenol (IPR) administration on them. For the experiment 1, several granules of HAP were implanted in the submandibular glands of rats and for another experiment 2, chronic IPR administration was carried out to rats implanted HAP. The surrounding tissues of HAP implanted and the insides of its pores were observed and analyzed with a light microscope, an electron microscope and an analytical electron microscope one and three days, and five, eight and ten weeks after treatment. The results were as follows: 1. The outer layer of HAP was encapsulated by granulation tissues due mainly to the infiltration of inflammatory cells one and three days after treatment. Subsequently, the encapsulation was further enhanced by fibrous cells and collagen fibers, whereas no obstructive reactions were seen in the surrounding tissues of HAP implanted. 2. From the first day after treatment, tissue fluid-like matrix substances permeated inside HAP and at the same time, blood cells, phagocytic and mesenchymal cells were detected within the whole HAP. 3. Especially, in the layer within 100-200 microns inside the pores of HAP, a number of fibroblasts, collagen fibers and osteoblast-like cells were observed. 4. Within the pores with cells infiltrated into HAP, a layer, suggestive of the precipitation of calcium-phosphate salts, was formed from one week after treatment. By five weeks, particularly within the layer, amorphous substances with the high density were observed in general and, by eight and ten weeks, the substances were further increased in thickness. 5. By eight and ten weeks, amorphous substances with the high density were observed in a line with collagen fibers and around the cells within HAP. 6. The amorphous substances with the high density were calcified substances consisting of mainly Ca and P, as observed by an elemental analysis. 7. By administration of IPR, most of the acinar cells and the cells in the pores became degenerative after about five weeks and less calcified substances were observed along the collagen fibers. However, as seen in the experiment 1, calcified substances were also found in the precipitated layer within matrix-like substances of the pores.(ABSTRACT TRUNCATED AT 400 WORDS)


Guideline for resuscitation in cardiac arrest after cardiac surgery.
The Clinical Guidelines Committee of the European Association for Cardio-Thoracic Surgery provides this professional view on resuscitation in cardiac arrest after cardiac surgery. This document was created using a multimodal methodology for evidence generation including the extrapolation of existing guidelines from the International Liaison Committee on Resuscitation where possible, our own structured literature reviews on issues particular to cardiac surgery, an international survey on resuscitation hosted by CTSNet and manikin simulations of potential protocols. This protocol differs from existing generic guidelines in a number of areas, the most import of which are the following: successful treatment of cardiac arrest after cardiac surgery is a multi-practitioner activity with six key roles that should be allocated and rehearsed on a regular basis; in ventricular fibrillation, three sequential attempts at defibrillation (where immediately available) should precede external cardiac massage; in asystole or extreme bradycardia, pacing (where immediately available) should precede external cardiac massage; where the above measures fail, and in pulseless electrical activity, early resternotomy is advocated; adrenaline should not be routinely given; protocols for excluding reversible airway and breathing complications and for safe emergency resternotomy are given. This guideline is subject to continuous informal review, and when new evidence becomes available.


Idiopathic chronic diarrhea associated with dysbiosis in a captive cynomolgus macaque (Macaca fascicularis).
Chronic inflammatory enteric diseases occur commonly in humans and animals, especially in captive bred macaques. However, information about the etiology of idiopathic chronic inflammatory diarrhea in cynomolgus monkeys is limited. In this paper, we reported the unusual case of idiopathic chronic diarrhea in a captive cynomolgus monkey based on microbial, imaging, and microbiome examinations.


Fabrication and cellular biocompatibility of porous carbonated biphasic calcium phosphate ceramics with a nanostructure.
Microwave heating was applied to fabricate interconnective porous structured bodies by foaming as-synthesized calcium-deficient hydroxyapatite (Ca-deficient HA) precipitate containing H(2)O(2). The porous bodies were sintered by a microwave process with activated carbon as the embedding material to prepare nano- and submicron-structured ceramics. By comparison, conventional sintering was used to produce microstructured ceramics. The precursor particles and bulk ceramics were characterized by transmission electron microscopy (TEM), dynamic light scattering, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transformed infrared spectroscopy (FTIR) and mechanical testing. TEM micrographs and assessment of the size distribution showed that the needle-like precursor particles are on the nanoscale. SEM observation indicated that the ceramics formed by microwave sintering presented a structure of interconnective pores, with average grain sizes of approximately 86 and approximately 167nm. XRD patterns and FTIR spectra confirmed the presence of carbonated biphasic calcium phosphate (BCP), and the mechanical tests showed that the ceramics formed by microwave sintering had a compressive strength comparable to that obtained by conventional methods. Rat osteoblasts were cultured on the three kinds of BCP ceramics to evaluate their biocompatibility. Compared with the microscale group formed by conventional sintering, MTT assay and ALP assay showed that nanophase scaffolds promoted cell proliferation and differentiation respectively, and SEM observation showed that the nanoscale group clearly promoted cell adhesion. The results from this study suggest that porous carbonated biphasic calcium phosphate ceramics with a nanostructure promote osteoblast adhesion, proliferation and differentiation. In conclusion, porous carbonated BCP ceramics with a nanostructure are simple and quick to prepare using microwaves and compared with those produced by conventional sintering, may be better bone graft materials.


Effects of a 4-week intervention using semi-custom insoles on perceived pain and patellofemoral loading in targeted subgroups of recreational runners with patellofemoral pain.
Explore the effects of a 4-week intervention using semi-custom insoles in recreational runners with patellofemoral pain. Mixed methods. Seventeen (10 males and 7 females) recreational runners. Laboratory. Participants were separated into specific subgroups, then provided with a pair of semi-custom insoles, for a period of 4-weeks. Lower extremity kinetics/kinematics during running at 4.0 m/s were obtained. In addition, knee pain was examined using the Knee injury and Osteoarthritis Outcome Score-Patellofemoral scale (KOOS-PF). Data were collected before and after wearing the insoles for 4-weeks. Significant improvements were shown for KOOS-PF in both subgroups (strong: (pre) = 63.84 & (post) = 71.49 and weak and tight: (pre) = 53.03 & (post) = 72.73), although only improvements in the weak and tight group exceeded the minimum clinically important difference (MCID). In addition, significant reductions in peak patellofemoral stress were shown in both subgroups (strong: (pre) = 6.82 & (post) = 6.39KPa/BW and weak and tight: (pre) = 7.66 & (post) = 6.28KPa/BW), although only reductions in the weak and tight group exceeded the MCID. Semi-custom insoles may be a mechanism to reduce patellofemoral pain symptoms in recreational runners from the weak and tight subgroup. It is proposed that this improvement was mediated through reductions in patellofemoral loading in this subgroup.


Distribution of somatostatin receptor type 2 in the rat: immunohistochemical study.
Somatostatin receptor type 2 (SSTR-2) was identified immunohistochemically in the rat tissues using specific antipeptide antiserum raised in New Zealand white rabbits immunized with a conjugate of synthetic SSTR-2 peptide (31-41) with bovine serum albumin. Immunohistochemical analysis was performed by avidin-biotin complex method. SSTR-2 immunoreactivity was visualized in the central nervous system and anterior pituitary thus supporting previous investigations of SSTR-2 distribution using in vitro autoradiographic ligand binding. Significant stain was detected in neural perikarya, axons and dendrites as well as in many cells of retina, adrenal medulla, gastric and duodenal mucosa, Auerbach's nervous branch and Meíssner's nervous branch of the stomach, small intestine and colon. When using antiserum preincubated with synthetic SSTR-2 peptide (31- 41) or rat anterior pituitary homogenate which contains SSTR-2 peptide, no significant stain of the anterior pituitary or neurons in the hypothalamus was detected. These findings suggest that SSTR-2 is widely distributed and that the method used is valuable in studying the distribution of SSTR-2 in rats.


Outcomes of the Ilizarov frame use in elderly patients.
The use of circular frame is widely accepted. This is an outcome review on use of circular Ilizarov frame in elderly patients. Data from all patients treated with an Ilizarov circular frame between January 2002 and December 2014, who were 65 years of age or over at surgery was collected. Seventy Ilizarov circular frames were applied during this period in our unit at a mean age of 71.2 years. Clinical, radiological and quality of life questionnaire (SF-12) data were gathered. Mortality, complication and revision data were also collected. Indications of application of Ilizarov frame were fractures (53%), non-unions (19%), deformity correction (7%) and ankle fusions (21%). Mean period of time in the frame was 184.4 ± 84.2 days. Mortality and complication rates were low (5-7%) at a mean follow-up 4.2 years. There was no case of septic arthritis or newly induced deep infection. Physical and Mental components of SF-12 questionnaire returned to normal for that age group. There was no difference between the subgroups (tibia plateau fractures, pilon fractures, ankle fusions, non-unions, deformity correction and miscellaneous trauma) concerning the physical and mental subjective (PCS and MCS SF-12 component) outcomes (p > 0.05). Ilizarov circular frame as a definitive treatment of many kinds of trauma and orthopaedic conditions can be safely and reliably used in the elderly with good quality of life results.


Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial.
Garlic is widely promoted as a cholesterol-lowering agent, but efficacy studies have produced conflicting results. Garlic supplements differ in bioavailability of key phytochemicals. We evaluated the effect of raw garlic and 2 commonly used garlic supplements on cholesterol concentrations in adults with moderate hypercholesterolemia. In this parallel-design trial, 192 adults with low-density lipoprotein cholesterol (LDL-C) concentrations of 130 to 190 mg/dL (3.36-4.91 mmol/L) were randomly assigned to 1 of the following 4 treatment arms: raw garlic, powdered garlic supplement, aged garlic extract supplement, or placebo. Garlic product doses equivalent to an average-sized garlic clove were consumed 6 d/wk for 6 months. The primary study outcome was LDL-C concentration. Fasting plasma lipid concentrations were assessed monthly. Extensive chemical characterization of study materials was conducted throughout the trial. Retention was 87% to 90% in all 4 treatment arms, and chemical stability of study materials was high throughout the trial. There were no statistically significant effects of the 3 forms of garlic on LDL-C concentrations. The 6-month mean (SD) changes in LDL-C concentrations were +0.4 (19.3) mg/dL (+0.01 [0.50] mmol/L), +3.2 (17.2) mg/dL (+0.08 [0.44] mmol/L), +0.2 (17.8) mg/dL (+0.005 [0.46] mmol/L), and -3.9 (16.5) mg/dL (-0.10 [0.43] mmol/L) for raw garlic, powdered supplement, aged extract supplement, and placebo, respectively. There were no statistically significant effects on high-density lipoprotein cholesterol, triglyceride levels, or total cholesterol-high-density lipoprotein cholesterol ratio. None of the forms of garlic used in this study, including raw garlic, when given at an approximate dose of a 4-g clove per day, 6 d/wk for 6 months, had statistically or clinically significant effects on LDL-C or other plasma lipid concentrations in adults with moderate hypercholesterolemia.


Examining the impact of a distance education MPH program: a one-year follow-up survey of graduates.
This article addresses the critical issue of measuring impact of a distance education Master of Public Health degree program on public health practitioners. It is based on an online survey of the 49 graduates of the Public Health Leadership Program at the School of Public Health of the University of North Carolina at Chapel Hill. The survey was carried out 1-year postgraduation and had a 73% response rate. Results indicated that graduates continued to have a high level of satisfaction with the program; 97% of respondents indicated they would recommend the program to others, and 75% said that their overall opinion about the program had increased since graduation. On a scale of 1 to 10, 79% of respondents rated the program with a score of 8 or higher in terms of the impact of the program on their ability to do their current job. Regarding new opportunities, 75% of respondents reported that they had new professional affiliations or service commitments, and 31% had job promotions since graduating. The methodology and results reported here may be a model for assessing the impact of a distance learning degree program for mid-career professionals. These results support the viability of a distance-education format for providing necessary training at the master's level for the public health workforce.


Effective photodegradation of methomyl pesticide in concentrated solutions by novel enhancement of the photocatalytic activity of TiO2 using CdSO4 nanoparticles.
Annihilation of electrons-holes recombination process is the main remedy to enhance the photocatalytic activity of the semiconductors photocatalysts. Doping of this class of photocatalysts by foreign nanoparticles is usually utilized to create high Schottky barrier that facilitates electron capture. In the literature, because nonpolar nanoparticles (usually pristine metals, e.g., Ag, Pt, Au, etc.) were utilized in the doping process, the corresponding improvement was relatively low. In this study, CdSO4-doped TiO2 nanoparticles are introduced as a powerful and reusable photocatalyst for the photocatalytic degradation of methomyl pesticide in concentrated aqueous solutions. The utilized CdSO4 nanoparticles form polar grains in the TiO2 matrix due to the electrons leaving characteristic of the sulfate anion. The introduced nanoparticles could successfully eliminate the harmful pesticide under the sunlight radiation within a very short time (less than 1 h), with a removal capacity reaching 1,000 mg pesticide per gram of the introduced photocatalyst. Moreover, increase in the initial concentration of the methomyl did not affect the photocatalytic performance; typically 300, 500, 1,000, and 2,000 mg/l solutions were completely treated within 30, 30, 40, and 60 min, respectively, using 100 mg catalyst. Interestingly, the photocatalytic efficiency was not affected upon multiple use of the photocatalyst. Moreover, negative activation energy was obtained which reveals super activity of the introduced photocatalyst. The distinct photocatalytic activity indicates the complete annihilation of the electrons-holes recombination process and abundant existence of electrons on the catalyst surfaces due to strong electrons capturing the operation of the utilized polar CdSO4 nanoparticles. The introduced photocatalyst has been prepared using the sol-gel technique. Overall, the simplicity of the synthesizing procedure and the obtained featured photocatalytic activity strongly recommend the introduced nanoparticles to treat the methomyl-containing polluted water.


Transcatheter valve-in-valve replacement of degenerated bioprosthetic aortic valves: a single Australian Centre experience.
Patients with degenerated surgical bioprosthetic valves may be at high risk for further surgery because of age, comorbidities and the difficulties of repeat procedures. Percutaneous valve-in-valve implantation offers what may be a simpler and safer procedure. From May 2009 to March 2014 at the Prince Charles Hospital 1625 patients underwent surgical aortic valve replacement while 262 underwent transcatheter aortic valve implantation. Twelve patients had valve-in-valve implants for degenerated bioprosthetic aortic valves. These implants were deployed successfully without major valvular or paravalvular regurgitation. There were no periprocedural deaths, myocardial infarcts, neurological events or major vascular complications. Two patients died after 1624 and 1319days. Median survival for the remainder is 581days; they are stable with New York Heart Association class I/II functional status although 4 have a degree of patient-prosthesis mismatch, one has moderate aortic regurgitation and one required surgery for a late aortic dissection. Transcatheter valve-in-valve implantation is safe and effective treatment for patients with failed bioprosthetic aortic valves for whom reoperation is considered to be hazardous.


Evidence that RNA silencing-mediated resistance to beet necrotic yellow vein virus is less effective in roots than in leaves.
In plants, RNA silencing is part of a defense mechanism against virus infection but there is little information as to whether RNA silencing-mediated resistance functions similarly in roots and leaves. We have obtained transgenic Nicotiana benthamiana plants encoding the coat protein readthrough domain open reading frame (54 kDa) of Beet necrotic yellow vein virus (BNYVV), which either showed a highly resistant or a recovery phenotype following foliar rub-inoculation with BNYVV. These phenotypes were associated with an RNA silencing mechanism. Roots of the resistant plants that were immune to foliar rub-inoculation with BNYVV could be infected by viruliferous zoospores of the vector fungus Polymyxa betae, although virus multiplication was greatly limited. In addition, virus titer was reduced in symptomless leaves of the plants showing the recovery phenotype, but it was high in roots of the same plants. Compared with leaves of silenced plants, higher levels of transgene mRNAs and lower levels of transgene-derived small interfering RNAs (siRNAs) accumulated in roots. Similarly, in nontransgenic plants inoculated with BNYVV, accumulation level of viral RNA-derived siRNAs in roots was lower than in leaves. These results indicate that the RNA silencing-mediated resistance to BNYVV is less effective in roots than in leaves.


Localization of UDP glucuronosyltransferase gene(s) on mouse chromosome 5.
The drug-metabolizing UDP glucuronosyltransferases are encoded by genes which constitute a multigene family. One rat gene subfamily codes for at least four constitutive enzyme forms, including those which glucuronidate the androgenic steroids testosterone (UDPGTr-3) and androsterone (UDPGTr-4). In the present study, UDPGTr-3 and UDPGTr-4 cDNAs were used to demonstrate that an homologous subfamily is present in the mouse genome. Using mouse X Chinese hamster somatic cell hybrids, we mapped at least one gene of this UDP glucuronosyltransferase subfamily (UDPGTr-3) to mouse chromosome 5 and suggest the name as the Udpgt-3 locus.


Role of particle size in assessment of physico-chemical properties and trace elements of Indian fly ash.
In this paper, the effect of particle size on the physico-chemical, mineralogical, and leaching behavior of Indian fly ash was studied. Experiments were carried out to study the leaching of different elements such as Mg, Cr, Zn, Pb, Mn, Fe, Cu, Co, Mo, and Ni from Indian fly ash. During the experiments, the liquid-to-solid (L/S) ratio of the fly ash was taken as 9/1, 8/2, 7/3, 3/2, 1/1, and 2/3. The effect of four different particle size ranges (below 53, 53-75, 75-106, and 106-150 μm) of fly ash was analyzed. The ASTMD-3987 method was used to analyze the presence of trace elements from fly ash. In the ASTM D-3987 method, distilled water was used for extraction of leachate. Fly ash slurry samples were agitated in a lubricating type temperature-controlled Remi orbital shaker for a time duration of 18 hours with speed of 100 revolutions per minute (rpm) at a temperature of 25ºC. Distilled water does not save cost as well as being easily available. The leaching test of trace elements from fly ash was investigated at different pH conditions in order to predict the environmental effect from the ash disposal on the groundwater quality. Results revealed that pH of slurry suspension increases with increase in particle size. The pH value of fly ash slurries was negligibly affected by the decrease in L/S ratio for all particle sizes. Fine particles of fly ash produce a more harmful effect as compared to the coarser range of fly ash particles.


Arthroscopic chondral cyst excision in a stiff Perthes' hip.
Persistent hip stiffness in Perthes' disease indicates a poor prognosis and is a therapeutic challenge. We report a case of a 13-year-old boy with a stiff Perthes' hip that was nonresponsive to prolonged nonsurgical treatment. Imaging revealed Catterall group IV Perthes' disease in an advanced reossification stage, with a focal defect in the weight-bearing area of the capital femoral epiphysis. A focal, compressible chondral elevation was detected on hip arthroscopy; on incision, flocculent fluid was released. After the cyst was excised, microfracture revascularization of the chondral defect was undertaken. Postoperatively, the patient had immediate pain relief, correction of deformity, and restoration of painless range of motion; this has continued for 4 years since surgery was performed. Persistence of an unhealed necrotic segment in Perthes' disease has traditionally been associated with osteochondritis dissecans; however, in this case, the unhealed and nonossified segment produced an elevated painful chondral cyst that caused spasm and stiffness of the hip. Although 2 distinct types of chondral lesions have been described in Perthes' disease, stiffness arising because of these lesions has not been reported. Patients with this unusual third type of chondral lesion of the capital femoral epiphysis, which causes persistent stiffness in Perthes' hip, may be identified and successfully treated with the use of arthroscopic techniques.


Pure neural leprosy: steroids prevent neuropathy progression.
Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats leprosy infection but is insufficient in arresting or preventing the nerve damage that causes impairments and disabilities. This case-series study evaluates the benefits of the combined use of steroids and MDT in preventing nerve damage in patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88% male aged 20-79 years, median=41) received a daily morning dose of 60 mg prednisone (PDN) that was gradually reduced by 10 mg during each of the following 5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or PCR. A low prevalence (8.3%) of reaction was observed after release from treatment. However, most of the clinical parameters showed significant improvement; and a reduction of nerve conduction block was observed in 42% of the patients. The administration of full-dose PDN improved the clinical and electrophysiological condition of the PNL patients, contributing to the prevention of further neurological damage.


The human coronary collateral circulation.
Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. Well-developed coronary collateral arteries in patients with coronary artery disease (CAD) mitigate myocardial infarcts and improve survival. Collateral arteries preventing myocardial ischaemia during brief vascular occlusion are present in 1/3 of patients with CAD. Among individuals without relevant coronary stenoses, there are preformed collateral arteries preventing myocardial ischaemia in 20-25%. Collateral flow sufficient to prevent myocardial ischaemia during coronary occlusion amounts to double dagger25% of the normal flow through the open vessel. Myocardial infarct size, the most important prognostic determinant after such an event, is the product of coronary artery occlusion time, area at risk for infarction and the inverse of collateral supply. Coronary collateral flow can be assessed only during vascular occlusion of the collateral-receiving artery. The gold standard for coronary collateral assessment is the measurement of intracoronary occlusive pressure- or velocity-derived collateral flow index expressing collateral as a fraction of flow during vessel patency. Approximately one of five patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting. Therapeutic promotion of collateral growth is a valuable treatment strategy in those patients. Promotion of collateral growth should aim at inducing the development of large conductive collateral arteries (i.e. arteriogenesis) and not so much the sprouting of capillary like vessels (i.e. angiogenesis). Large conductive collateral arteries appear to be effectively promoted via the activation of monocytes/macrophages by means of granulocyte-colony stimulating factor or of augmenting coronary flow velocity.


Interpersonal problems and personality: using three factor solutions.
Attempting to bridge the gap between psychotherapy research on interpersonal discord and personality research on factors of normal and abnormal personality, the present study uses personality factors to predict interpersonal problems. Eysenck's P-E-N (Psychoticism-Extraversion-Neuroticism) model of personality and its correspondent index, the Eysenck Personality Questionnaire-Revised is used as a schema from which to conceptualize and measure personality. Horowitz's Inventory of Interpersonal Problems, which includes six problems commonly reported by psychotherapy patients at intake (hard to be assertive, hard to be submissive, hard to be intimate, hard to be sociable, too controlling, and too responsible), was used as an index of interpersonal distress. Hierarchical multiple regression, in which the most significant predictor was entered into the equation first, indicate significant prediction of various problems by the personality factors considered here. Results are discussed in the context of interpersonal theory.


Pediatric rheumatology for the adult rheumatologist.
Although many manifestations of rheumatic diseases in children are similar to those in adults, there exist important differences. These include variations in presentation and complications, differential diagnoses to consider, medication side effects, impact on growth, and psychosocial issues. As there is a US and worldwide shortage of pediatric rheumatologists, many children with rheumatic illnesses are cared for by other physicians, especially by adult rheumatologists. This article is aimed toward educating the adult rheumatologist in 4 key areas of childhood rheumatic disease: juvenile idiopathic arthritis, other rheumatic and inflammatory illnesses seen primarily in the pediatric population, differences in rheumatic diseases common to both adults and children, and psychosocial issues.


Discovery of potent and selective inhibitors of calmodulin-dependent kinase II (CaMKII).
We hereby disclose the discovery of inhibitors of CaMKII (7h and 7i) that are highly potent in rat ventricular myocytes, selective against hERG and other off-target kinases, while possessing good CaMKII tissue isoform selectivity (cardiac γ/δ vs. neuronal α/β). In vitro and in vivo ADME/PK studies demonstrated the suitability of these CaMKII inhibitors for PO (7h rat F = 73%) and IV pharmacological studies.


Retinociliary vein associated with a craniopharyngioma.
A 60-year-old white man had a diagnosis of craniopharyngioma made in 1945. Three operations for partial tumor removal were performed in 1951, 1957, and 1962. Ophthalmoscopy and fluorescein angiography revealed bilateral optic atrophy and a large retinociliary vein in the left eye. The present report is the only example of a retinociliary vein documented with photography and fluorescein angiography. It is not possible to ascertain whether this retinociliary vein is an acquired malformation or a congenital development anomaly. The extreme rarity of this entity, though, suggests that this retinociliary vein developed as a result of obstruction, by the craniopharyngioma, to the retinal venous outflow during early development.


Oxidative damage to plant DNA in relation to growth conditions.
In this study we investigated the level of 8-oxo-2'-deoxyguanosine (8-oxodG) in DNA of Cardamine pratensis plants subjected to different growth conditions trying to answer the question whether factors like light and water accessibility or low temperature may have an impact on the total DNA oxidative damage. The level of this modified nucleoside was determined using HPLC coupled to UV absorbance and electrochemical detection (HPLC-UV-EC). We did not observe any statistically significant differences in 8-oxodG level between DNA of etiolated and light exposed plants as well as between DNA of regularly watered and drought-subjected plants. In contrast, we have shown that chilling (1 degree C for 28 h) brings about the increase of 8-oxodG level in DNA.


Energy metabolism during cold ischemia and reperfusion in rat small intestinal transplantation: comparison of jejunal and ileal grafts.
In segmental small intestinal transplantation, the question as to whether the jejunum or ileum is the better graft remains unclear. The authors investigated this question regarding nutrition, blood chemistry, and adaptation. The authors compared the jejunum and ileum as the proper portion of segmental graft in rat small intestinal transplantation, regarding energy metabolism both during cold preservation and after reperfusion using high-performance liquid chromatography, as well as histological examination. In a cold preservation study, the concentrations of adenosine triphosphate (ATP) in the jejunum versus ileum at 0, 6, 12, 24, and 48 hours of cold preservation were 1.98 +/- 0.93 versus 1.83 +/- 0.84, 0.79 +/- 0.51 versus 0.55 +/- 0.41, 0.60 +/- 0.41 versus 0.58 +/- 0.45, 0.38 +/- 0.28 versus 0.47 +/- 0.39, and 0.44 +/- 0.26 versus 0.55 +/- 0.29 (micromol/g dry weight), respectively. There were no significant differences between the jejunum and ileum at any times of preservation. Adenosine monophosphate (AMP), adenosine diphosphate (ADP), total adenine nucleotides (TAN), and energy charge (EC) also showed no significant differences between the jejunum and ileum at any times of preservation. In the reperfusion study, the concentrations of ATP in jejunum versus ileum 30 minutes after reperfusion after 6, 12, and 24 hours of cold preservation were 0.68 +/- 0.19 versus 0.50 +/- 0.17, 0.71 +/- 0.51 versus 0.42 +/- 0.14, and 0.93 +/- 0.29 versus 0.75 +/- 0.47 (micromol/g dry weight), respectively. Each value was slightly higher in the jejunum than that in the ileum; however, there were no statistically significant differences. TAN showed the same changes as ATP. No significant differences were found between the jejunum and ileum in either AMP, ADP, or EC. The histological findings both just before and 30 minutes after reperfusion were also compared. However, no evident differences were found between the jejunum and ileum. These results thus suggest that no significant differences exist between the jejunum and ileum regarding energy metabolism either during cold preservation or after reperfusion in small intestinal transplantation.


Sonographic-detected joint effusion compared with physical examination in the assessment of sacroiliac joints in spondyloarthritis.
An observational case-control study was designed to analyse the discriminative value of ultrasound (US)-detected joint effusion compared with physical examination in the assessment of sacroiliac joints (SIJ) in patients with spondyloarthropathy (SpA) with or without inflammatory back pain (IBP). 45 patients with SpA, classified according to European Spondylarthropathy Study Group criteria, and 30 healthy volunteers were studied. All patients had clinical evaluation of the SIJ, Bath ankylosing spondylitis (AS) metrology index, Bath AS disease activity index, Bath AS functional index, health assessment questionnaire, patient's and physician's visual analogue scale on global disease activity. Ultrasound showed joint effusion in 38.9% of SIJ of patients with SpA and in 1.7% of SIJ of controls (p<0.001). The presence of IBP was significantly associated with SIJ effusion assessed by US alone or plus at least one SIJ test. SIJ effusion assessed by US alone or plus at least one SIJ test had a positive likelihood ratio (LR) (2.67 and 4.04, respectively) for the presence of IBP higher than LR of single clinical tests. Positive sacral sulcus test, iliac gapping and midline sacral thrust test were associated with SIJ effusion assessed by US, but all clinical tests, singly and in various combinations, had a low LR for the presence of SIJ effusion assessed by US. The study suggests that high resolution sonography is useful in the assessment of SIJ involvement in SpA, resulting in images that are fast and inexpensive and may locate, complementing the physical examination, the origin of IBP.


Postoperative radiation therapy for low-grade glioma: patterns of care between 1998 and 2006.
The role of postoperative radiotherapy (PORT) in the management of low-grade glioma remains controversial. An analysis using data from the European Organization for Research and Treatment of Cancer 22844/22845 studies concluded that several factors portend a poor prognosis: age ≥40 years, astrocytoma histology, tumor size ≥6 cm, tumor crossing midline, and preoperative neurologic deficits. PORT may benefit patients with high-risk features. The aim of this study was to assess temporal trends and determinants of the use of PORT. By using data from the Surveillance, Epidemiology, and End Results program, the authors identified 1127 adult patients diagnosed with low-grade glioma (World Health Organization grade I and II) who underwent surgical resection between January 1, 1998 and December 31, 2006. The primary outcome was receipt of PORT. The authors performed multivariate logistic regression to examine the association between clinical, patient, and demographic characteristics and receipt of PORT. Receipt of PORT declined during the study period, from 64% of patients in 1998 to 36% of patients in 2006. On multivariate analysis, significant predictors of receipt of PORT were age ≥40 years, tumor crossing midline, and partial surgical resection. The use of PORT for patients with low-grade glioma has declined in the period from 1998 to 2006 for both low-risk and high-risk patients.


Perioperative adverse events attributed to α2-adrenoceptor agonists in patients not at risk of cardiovascular events: systematic review and meta-analysis.
Several systematic reviews have reported the benefits of perioperative α2-adrenoceptor agonist use for various conditions, but safety evidence is poorly documented. We performed a systematic review focusing on adverse events. We searched the MEDLINE, Embase, LILACS, Cochrane, and Clinical Trials Register databases for RCTs comparing the effects of α2-adrenoceptor agonists and placebo during non-cardiovascular surgery under general anaesthesia, for any indication, in patients not at risk of cardiovascular events. The primary outcome was the incidence of severe adverse events during or after α2-adrenoceptor agonist administration. The secondary endpoints were other adverse events. A meta-analysis was carried out on the combined data. Evidence quality was rated by the Grading of Recommendations Assessment, Development and Evaluation method. We included 56 studies (4868 patients). Our review, based on moderate-quality evidence, revealed that hypotension occurred frequently during the preoperative and postoperative periods, for both clonidine and dexmedetomidine. Bradycardia was reported only with dexmedetomidine. In contrast, dexmedetomidine seemed to protect against intraoperative hypertension and tachycardia. Subgroup analysis suggested that the risk of hypotension and bradycardia persisted after cessation of treatment. Interestingly, intraoperative hypotension and postoperative bradycardia were not observed with a bolus dosage of dexmedetomidine less than 0.5 μg kg-1 or with continuous administration alone. Pooled data for the incidence of adverse events associated with use of α2-adrenoceptor agonists in various perioperative contexts provide high-confidence evidence for a risk of hypotension and bradycardia, and protective effects against hypertension and tachycardia. CRD42017071583.


Systemic uptake inhibition decreases serotonin release via somatodendritic autoreceptor activation.
In vivo microdialysis was used to examine the effects of peripheral uptake inhibition on extracellular serotonin (5-HT). Previous results from this lab indicated that systemic fluoxetine caused a decrease in 5-HT when terminal uptake was inhibited by local infusion of the uptake blocker. We hypothesized that the decrease in 5-HT levels in the terminal region was due to an increase in 5-HT in the vicinity of the inhibitory somatodendritic autoreceptors in the dorsal raphe nucleus (DRN). To test this prediction, rats were implanted with probes in both the basal diencephalon (a nerve terminal region) and the DRN (the cell body region). Fluoxetine (10 mg/kg i.p.) increased extracellular 5-HT, in a depolarization-dependent manner, by approximately 140% in both areas. In a separate experiment, fluoxetine was infused into the diencephalon overnight to block nerve terminal uptake sites. This pretreatment caused an eight- to 10-fold increase in 5-HT levels. Subsequent systemic fluoxetine, sertraline, or paroxetine, produced a 50% decrease in extracellular 5-HT in the diencephalon, presumably due to activation of the 5-HT1A somatodendritic autoreceptors. Consistent with this hypothesis, systemic administration of the 5-HT1 antagonists spiperone, penbutolol, or WAY100135 reversed the fluoxetine-induced decrease in 5-HT to approximately 85% of the pre-fluoxetine baseline levels. Likewise, pretreatment with penbutolol, but not selective beta-adrenergic antagonists, blocked the fluoxetine-induced decrease in release. These findings suggest that the ability of acute systemic 5-HT uptake inhibition to elevate nerve terminal 5-HT is limited by autoreceptor activation following elevation of 5-HT in the DRN.


Characterization of neurons in the area of the medullary lateral reticular nucleus responsive to noxious visceral and cutaneous stimuli.
In halothane-anesthetized rats, 283 caudal medullary neurons responsive to colorectal distension (CRD) were characterized using extracellular electrodes. Neurons inhibited by CRD (n = 82) were in the area dorsal to the lateral reticular nucleus (LRN). Most neurons excited by CRD (n = 130) were located within or immediately adjacent to the LRN, were excited by noxious heat and/or noxious pinch of at least half the body surface and were called bilateral nociceptive specific (bNS) neurons. bNS neurons had accelerating responses to graded CRD (threshold: 20 +/- 2 mmHg). Ten of twelve bNS neurons tested could be antidromically activated by electrical stimulation of the midline cerebellum. Other neurons excited by CRD (n = 71) had mixed responses to cutaneous stimuli and were generally located in the area dorsal to the LRN. Increases in blood pressure due to intravenous phenylephrine did not significantly alter the spontaneous activity of neurons excited by CRD, but altered spontaneous activity (12 excited, four inhibited) in all neurons tested which were inhibited by CRD. Decreases in blood pressure produced by intravenous nitroprusside produced a reciprocal response in most neurons inhibited by CRD and had a delayed onset (20-30 s after bolus administration) excitatory effect on 21 of 27 units excited by CRD. Combined with other studies, these data suggest a role for neurons within and adjacent to the LRN in the modulation of visceral nociception. They also implicate a role for the cerebellum in visceral nociceptive processing.


Teicoplanin and rifampicin singly and in combination in the treatment of experimental Staphylococcus epidermidis endocarditis in the rabbit model.
Teicoplanin and rifampicin were evaluated as single and combined agents in the treatment of endocarditis due to Staphylococcus epidermidis in the rabbit model. Rabbits were treated for ten days and the number of bacteria in vegetations determined. At the end of ten days the geometric mean number of bacteria in the vegetations were 5.53 X 10(8), 6.68 X 10(6). 1.10 X 10(4), 2.57 X 10(1) cfu/g of vegetation for control, teicoplanin, rifampicin, and teicoplanin plus rifampicin groups respectively. The MIC and MBC values of the S. epidermidis isolates were 0.78 mg/l for teicoplanin and less than or equal to 0.10 mg/l for rifampicin. In the rifampicin treated group three post-treatment isolates of S. epidermidis tested exhibited marked resistance to rifampicin with MIC and MBC values greater than or equal to 200 mg/l. Teicoplanin and rifampicin were both effective as single agents in the clearance of S. epidermidis from the bloodstream. Rifampicin was more effective than teicoplanin in the clearance of S. epidermidis from vegetations but teicoplanin in combination with rifampicin was more effective than either drug alone.


Injection-Molded Microfluidic Device for SERS Sensing Using Embedded Au-Capped Polymer Nanocones.
To enable affordable detection and diagnostic, there is a need for low-cost and mass producible miniaturized sensing platforms. We present a fully polymeric microfluidic lab-on-a-chip device with integrated gold (Au)-capped nanocones for sensing applications based on surface-enhanced Raman spectroscopy (SERS). All base components of the device were fabricated via injection molding (IM) and can be easily integrated using ultrasonic welding. The SERS sensor array, embedded in the bottom of a fluidic channel, was created by evaporating Au onto IM nanocone structures, resulting in densely packed Au-capped SERS active nanostructures. Using a Raman active model analyte, trans-1,2-bis-(4-pyridyl)-ethylene, we found a surface-averaged SERS enhancement factor of ∼5 × 106 with a relative standard deviation of 14% over the sensor area (2 × 2 mm2), and a 18% signal variation among substrates. This reproducible fabrication method is cost-effective, less time consuming, and allows mass production of fully integrated polymeric, microfluidic systems with embedded high-density and high-aspect ratio SERS sensor.


Pronator teres reflex: reliability and normal value.
The pronator reflex has been used clinically and electrophysiologically to evaluate the sixth and seventh cervical roots (C-6, C-7). This has been proven to be the result of stretching the pronator teres muscle. We examined 25 healthy individuals with surface electromyogram to establish electrophysiologically the reproducibility and reliability of this reflex, in addition to finding the 95% confidence interval (C.I.) for the latency for both males and females and to correlate it with the arm length. Standard procedure was used for all people. To elicit the pronator teres reflex, the volar report of the distal radius was struck by the hammer with the forearm in neutral position and the elbow flexed at 90 degrees. The response was pronation of the forearm. A reproducible diphasic response was found in all individuals. The mean latency was 15.9 (+/-1.3) ms with the 95% C.I. 16.8 for females and 17.4 (+/- 1.4) ms with the 95% C.I. 18.7 for males. The data were collected to be used for further evaluation of C-6, C-7 radiculopathy.


Measurement of specific multiplication of an oncolytic and a nononcolytic strain of Clostridium butyricum inside the tumour UVT 15264 of the mouse.
Clostridium butyricum was recultivated from tumour material after treatment of tumour-bearing mice with spores and counted by soft agar colony technique. The oncolytic strain Cl. butyricum H8 grows inside the tumour UVT 15264 up to 8 X 10(8)/g during 48 h. In this time part of tumour became lysed. Multiplication inside of this tumour by the tumour specific but nononcolytic strain Cl. butyricum CNRZ 528 could not be detected by application counting technique. Combination of spore treatment with antibiotic chemotherapy in dosage able to prevent oncolysis or in dosage to reduce them corresponds with loss of clostridial multiplication or with reduced vegetative multiplication respectively.


Pharmacological modulation of cell death in organ transplantation.
New options to pharmacologically modulate fundamental mechanisms of regulated cell death are rapidly evolving and found first clinical applications in cancer therapy. Here, we present an overview on how the recent advances in the understanding of the biology and pharmacology of cell death might influence research and clinical practice in solid organ transplantation. Of particular interest are the novel opportunities related to organ preservation and immunomodulation, which might contribute to promote organ repair and to develop more selective ways to modulate allogeneic immune responses to prevent rejection and induce immunological tolerance.


Reducing costs at the end of life through provider incentives for hospice care: A retrospective cohort study.
Costs of medical care have been found to be highest at the end of life. To evaluate the effect of provider reimbursement for hospice care on end-of-life costs. The policy expanded access to hospice care for end-stage renal disease patients, a policy previously limited to cancer patients only. This study employed a difference-in-differences analysis using a generalized linear model. The main outcome is inpatient expenditures in the last 30 days of life. A cohort of 151,509 patients with chronic kidney disease or cancer, aged 65 years or older, who died between 2005 and 2012 in the National Health Insurance Research Database, which contains all enrollment and inpatient claims data for Taiwan. Even as end-of-life costs for cancer are declining over time, expanding hospice care benefits to end-stage renal disease patients is associated with an additional reduction of 7.3% in end-of-life costs per decedent, holding constant patient and provider characteristics. On average, end-of-life costs are also high for end-stage renal disease (1.88 times higher than those for cancer). The cost savings were larger among older patients-among those who died at 80 years of age or higher, the cost reduction was 9.8%. By expanding hospice care benefits through a provider reimbursement policy, significant costs at the end of life were saved.


Synthesis, analytical characterization and bioactivity of Ag and Cu nanoparticles embedded in poly-vinyl-methyl-ketone films.
The electrosynthesis of copper and silver core-shell nanoparticles (NPs) by the sacrificial anode technique, employing tetraoctylammonium (TOA) salts as base electrolyte for the first time, is described. These surfactants were selected because they combine high NP stabilizing power with useful disinfecting properties. The resulting colloids were mixed with a solution of an inert dispersing polymer and used to prepare nanostructured composite thin films. The morphologies and chemical compositions of the nanomaterials were characterized by Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). The TEM reveals that the average core diameter of the metal NPs ranges between 1.7 and 6.3 nm, as a function of the nature of the metal and of the electrosynthesis conditions, and does not change significantly upon inclusion in the polymer matrix. An appreciable concentration of the metal is detected on the nanoparticle surface by XPS. High-resolution XP spectra indicate that both copper and silver are present at zero oxidation state in all of the materials (colloids and composite films). This demonstrates the high efficiency of the surfactant at controlling the morphology and the chemical composition of the nanodispersed metal in both the as-synthesized colloid and in the polymeric dispersion. The nanocoatings are shown to exert a marked inhibitory effect on the growth of eukaryote and prokaryote target microrganisms, and experimental evidence of a synergic disinfecting effect due to the surfactant and the nanodispersed metal is provided. On the basis of these stability and bioactivity results, it is clear that Cu-NPs and Ag-NPs are suitable for application in disinfecting or antifouling paint and coating formulations.


Isolation and sequence analysis of the gene encoding translation elongation factor 3 from Candida albicans.
The structural gene encoding translation elongation factor 3 (EF-3) has been cloned from a Candida albicans genomic library by hybridization to a Saccharomyces cerevisiae probe containing the Saccharomyces gene, YEF3 (Sandbaken et al., 1990b). The sequences were shown to be functionally homologous to the Saccharomyces gene by three criteria: (1) a Saccharomyces strain transformed with a high copy plasmid containing CaEF3 sequences overproduces the EF-3 peptide two-fold; (2) extracts from this strain exhibit a two-fold increase in the EF-3-catalysed, ribosome-dependent ATPase activity (Kamath and Chakraburtty, 1988); and (3) the Candida gene complements a Saccharomyces null mutant. The coding region, identified by DNA sequencing, indicates that CaEF3 encodes a 1050 amino acid polypeptide having a potential molecular weight of 116,865 Da. This protein shows 77% overall identity to the Saccharomyces YEF3 gene, with a significantly greater identity (94%) concentrated in the region of the protein thought to contain the catalytic domain of EF-3 (Sandbaken et al., 1990a). The upstream non-coding region contains T-rich regions typical of many yeast genes and several potential RAP1/GRF1 elements shown to regulate expression of a number of translational genes (Mager, 1988). The data confirm a high degree of conservation for EF-3 among the two organisms.


A semi-precision cast splint for fixation following segmental osteotomies.
A method of fixation following intra-oral segmental osteotomies is presented. Immobilisation is obtained by a three-part cast splint connected by a semi-precision horizontal pin attachment. The advantages of this method are discussed.


Upper limb function is normal in patients with restless legs syndrome (Willis-Ekbom Disease).
Restless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is a sensorimotor-related sleep disorder. Little is known of the effect of RLS/WED on motor function. The current study investigated upper limb function in RLS/WED patients. We hypothesised that RLS/WED patients exhibit subtle changes in tremor amplitude but normal dexterity and movement speed and rhythmicity compared to healthy controls. RLS/WED patients (n=17, 59 ± 7 years) with moderate disease and healthy controls (n=17, 58 ± 6 years) completed screening tests and five tasks including object manipulation, maximal pinch grip, flexion and extension of the index finger (tremor assessment), maximal finger tapping (movement speed and rhythmicity assessment), and the grooved pegboard test. Force, acceleration, and/or first dorsal interosseus EMG were recorded during four of the tasks. Task performance did not differ between groups. Learning was evident on tasks with repeated trials and the magnitude of learning did not differ between groups. Hand function, tremor, and task learning were unaffected in RLS/WED patients. Patients manipulated objects in a normal manner and exhibited normal movement speed, rhythmicity, and tremor. Further research is needed to assess other types of movement in RLS/WED patients to gain insight into the motor circuitry affected and the underlying pathophysiology.


High-throughput cardiac safety evaluation and multi-parameter arrhythmia profiling of cardiomyocytes using microelectrode arrays.
Microelectrode arrays (MEAs) recording extracellular field potentials of human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) provide a rich data set for functional assessment of drug response. The aim of this work is the development of a method for a systematic analysis of arrhythmia using MEAs, with emphasis on the development of six parameters accounting for different types of cardiomyocyte signal irregularities. We describe a software approach to carry out such analysis automatically including generation of a heat map that enables quick visualization of arrhythmic liability of compounds. We also implemented signal processing techniques for reliable extraction of the repolarization peak for field potential duration (FPD) measurement even from recordings with low signal to noise ratios. We measured hiPS-CM's on a 48 well MEA system with 5minute recordings at multiple time points (0.5, 1, 2 and 4h) after drug exposure. We evaluated concentration responses for seven compounds with a combination of hERG, QT and clinical proarrhythmia properties: Verapamil, Ranolazine, Flecainide, Amiodarone, Ouabain, Cisapride, and Terfenadine. The predictive utility of MEA parameters as surrogates of these clinical effects were examined. The beat rate and FPD results exhibited good correlations with previous MEA studies in stem cell derived cardiomyocytes and clinical data. The six-parameter arrhythmia assessment exhibited excellent predictive agreement with the known arrhythmogenic potential of the tested compounds, and holds promise as a new method to predict arrhythmic liability.


[Risk factors associated with cardiac involvement in patients with dermatomyositis/polymyositis].
To identify risk factors associated with cardiac involvement (CI) in patients with dermatomyositis/polymyositis (DM/PM). Medical records of 129 DM/PM patients were reviewed retrospectively. The risk factors associated with CI in those patients were screened through Xt tests or independent tests before a multivariate logistic regression analysis was performed. ROC curves were constructed to determine diagnostic values of the identified risk factors. CI occurred in 59 (45. 74%) of DM/PM patients, with 41 (69. 49%) showing electrocardiographic (ECG) abnormality; 25 (42. 37%) showing ultrasonic cardiogram (UCG) abnormality; 8 (13. 56%) being diagnosed with heart failure, and 2 (3. 39%) being diagnosed with myocardial infarction. Eight (13.56%) of the patients with CI died. CI was more likely to occur in patients with an older age, having interstitial lung disease, antinuclear antibody (ANA) positive, and anti-Jo-1 antibody positive (P<0.05). The logistic regression analysis revealed that interstitial lung disease (beta=1. 554), aspartic aminotransferase/creatine kinases (AST/CK) ratio (beta=1.189), positive ANA (beta= 1. 172) and age (beta=0.042) were risk factors associated with CI (P<0. 05). Notable areas under ROC curve (0. 642) was found for AST/CK in determining CI in DM/PM patients (P<0. 05), albeit with low accuracy. A cut-off of AST/CK ratio at 0. 312 was identified as a reference point for determining CI in patients with DM/PM. Cardiac involvement is the most common complication of DM/PM, although the majority are subclinical. ECG and UCG are common tools for diagnosing cardiac involvement. Interstitial lung disease, AST/CK ratio, positive ANA and age are predictors of CI in DM/PM patients.


Evolutionary footprint of coevolving positions in genes.
The analysis of molecular coevolution provides information on the potential functional and structural implication of positions along DNA sequences, and several methods are available to identify coevolving positions using probabilistic or combinatorial approaches. The specific nucleotide or amino acid profile associated with the coevolution process is, however, not estimated, but only known profiles, such as the Watson-Crick constraint, are usually considered a priori in current measures of coevolution. Here, we propose a new probabilistic model, Coev, to identify coevolving positions and their associated profile in DNA sequences while incorporating the underlying phylogenetic relationships. The process of coevolution is modeled by a 16 × 16 instantaneous rate matrix that includes rates of transition as well as a profile of coevolution. We used simulated, empirical and illustrative data to evaluate our model and to compare it with a model of 'independent' evolution using Akaike Information Criterion. We showed that the Coev model is able to discriminate between coevolving and non-coevolving positions and provides better specificity and specificity than other available approaches. We further demonstrate that the identification of the profile of coevolution can shed new light on the process of dependent substitution during lineage evolution.


Medicare: the place to start delivery system reform.
The development of accountable care organizations (ACOs) is an appropriate goal for delivery system reform. The Medicare program can be instrumental in starting the necessary transformations in payment design, incentives, and delivery system structure. Payment reforms are critical; should come first; and may need to be substantial, cumulative in impact, and dramatic in design. Learning from successful models of physician-hospital integration and creating new models that can pass legal, regulatory, and antitrust concerns will be needed, if the promise of ACOs is to be fulfilled.


Alteration of cartilage mechanical properties in absence of β1 integrins revealed by rheometry and FRAP analyses.
Mechanical properties are essential for biological functions of the hyaline cartilage such as energy dissipation and diffusion of solutes. Mechanical properties are primarily dependent on the hierarchical organization of the two major extracellular matrix (ECM) macromolecular components of the cartilage: the fibrillar collagen network and the glycosaminoglycan (GAG)-substituted proteoglycan, mainly aggrecan, aggregates. Interaction of chondrocytes, the only cell type in the tissue, with the ECM through adhesion receptors is involved in establishing mechanical stability via bidirectional transduction of both mechanical forces and chemical signals. In this study, we aimed to determine the role of the transmembrane β1 integrin adhesion receptors in cartilage biomechanical properties by the use of genetic modification in mice. Costal cartilages of wild type and mutant mice lacking β1 integrins in chondrocytes were investigated. Cartilage compressive properties and solute diffusion were characterized by rheometric analysis and Fluorescence Recovery After Photobleaching (FRAP), respectively. Cartilage tissue sections were analyzed by histology, immunohistochemistry and transmission electron microscopy (TEM). At the histological level, the mutant costal cartilage was characterized by chondrocyte rounding and loss of tissue polarity. Immunohistochemistry and safranin orange staining demonstrated apparently normal aggrecan and GAG levels, respectively. Antibody staining for collagen II and TEM showed comparable expression and organization of the collagen fibrils between mutant and control cartilages. Despite the lack of gross histological and ultrastructural abnormalities, rheological measurements revealed that the peak elastic modulus in compression of mutant cartilage was 1.6-fold higher than the peak elastic modulus of wild-type sample. Interestingly, the diffusion coefficient within the mutant cartilage tissue was found to be 1.2-fold lower in the extracellular space and 14-fold lower in the pericellular (PCM) space compared to control. The results demonstrate that the absence of β1 integrins on the surface of chondrocytes increases the stiffness and modifies the diffusion properties of costal cartilage. Our data imply that β1 integrins-mediated chondrocyte-matrix interactions directly affect cartilage biomechanics probably by modifying physical properties of individual cells. This study thus highlights the crucial role of β1 integrins in the cartilage function.


Tympanoplasty and eustachian tube function.
In an attempt to assess the value of preoperative tubal testing in the selection of cases most likely to respond favourably to surgery, 100 ears with a central perforation following chronic otitis media were investigated. Tubal function was tested manometrically with different known tests. Postoperatively the healing and hearing results were correlated with the preoperative test results. No positive correlation was found between healing or hearing and tubal function. Postoperatively 50 ears were re-tested in a pressure chamber with a flow volume technique. It was found that the tubal function improves postoperatively in spite of no visible pathological changes in the aural end of the tube. Possible explanations are offered.


Return to the past: myocardial regeneration therapy.
In recent years, myocardial regeneration therapy has been the subject of intense research. Several different cell lines and routes of administration have been tested and the main mechanisms of action are known. A substantial amount of data is available not only from the bench, but also from the bedside. However, there are still many unanswered questions about the safety and efficacy of this treatment The future of this therapy is uncertain at present, but it unquestionably has great potential. We await the results of ongoing clinical trials in order to have a clearer view of this field of research.


Value patterns and content among families of Soviet immigrants: SYMLOG analysis.
The purpose of this qualitative study is to understand and compare two immigrant families whose children perceived their families to be well-functioning, and two families whose children perceived them to be poor-functioning. The method of analysis used for studying the values of the families is based on SYMLOG. Four families, who immigrated to Israel during the early seventies from the former USSR, and whose adolescents were born in Israel, were interviewed. The results show that in the two "well-functioning" families, there is a high degree of consensus on their values-those that they accept, as well as, those that they reject. The two "poor-functioning" families did not exhibit identical value patterns--neither in the values that they favor, nor in those that they reject. In terms of content, in the well-functioning families, there was a strong expression of two values: friendliness and the desirability of self-sacrifice in order to reach family goals. In contrast, in the poor-functioning families, the value of conservatism was salient. Finally, all four families expressed strong opposition to the values of strong individualism and nonconformity. Suggestions for family intervention are offered.


Ordering phthalocyanine-C60 fullerene conjugates on individual carbon nanotubes.
We report on the remarkable organization properties of a covalently-linked phthalocyanine-C(60) fullerene conjugate which is able to self-organize by means of non-covalent interactions on the outer wall of single-walled carbon nanotubes (SWCNTs).


Decreased Glasgow Coma Scale score does not mandate endotracheal intubation in the emergency department.
Decreased consciousness is a common reason for presentation to the emergency department (ED) and admission to acute hospital beds. In trauma, a Glasgow Coma Scale score (GCS) of 8 or less indicates a need for endotracheal intubation. Some advocate a similar approach for other causes of decreased consciousness, however, the loss of airway reflexes and risk of aspiration cannot be reliably predicted using the GCS alone. A survey of all poisoned patients with a decreased GCS who were admitted to an ED short-stay ward staffed by experienced emergency physicians, to establish the incidence of clinically significant aspiration or other morbidities and endotracheal intubation. A prospective, observational study was conducted of all patients admitted to the ED short-stay ward with a decreased level of consciousness (GCS < 15). The study included 73 patients with decreased consciousness as a result of drug or alcohol intoxication. The GCS ranged from 3 to 14, and 12 patients had a GCS of 8 or less. No patient with a GCS of 8 or less aspirated or required intubation. There was one patient who required intubation; this patient had a GCS of 12 on admission to the ward. This study suggests that it can be safe to observe poisoned patients with decreased consciousness, even if they have a GCS of 8 or less, in the ED.


Antistaphylococcal activity of amoxicillin and ticarcillin when combined with clavulanic acid. Evaluation of oxacillin-resistant and oxacillin-susceptible isolates.
The beta-lactamase inhibitor, clavulanic acid, was combined with amoxicillin and with ticarcillin for in vitro studies with 586 staphylococci: 97 stock cultures of oxacillin-resistant strains recovered before 1982, and 489 blood or wound isolates collected from 40 separate medical centers during 1987-1988 (300 were oxacillin resistant). Over 92% of the staphylococci produced beta-lactamase enzymes and were thus resistant to both penicillins. However, with the addition of clavulanic acid, oxacillin-susceptible strains were rendered susceptible to low concentrations of amoxicillin and ticarcillin. Staphylococcus aureus strains with borderline or partial borderline resistance to penicillinase-resistant penicillins occurred infrequently (72 of 325 S. aureus isolates). Those strains were susceptible to both clavulanic acid combinations, because their methicillin resistance is thought to be due to an excess beta-lactamase production. Strains with chromosomally mediated intrinsic heteroresistance were relatively resistant to both drug combinations. Minimal inhibitory concentration (MIC) breakpoints that best separated those heteroresistant strains from oxacillin-susceptible isolates were as follows: amoxicillin/clavulanic acid, less than or equal to 2.0/1.0 micrograms/ml for susceptible; and ticarcillin/clavulanic acid, less than or equal to 4.0/2.0 micrograms/ml for susceptible. When the broth was supplemented by 2% NaCl, MICs for both drug combinations were increased by less than one doubling dilution. Although oxacillin and methicillin broth microdilution tests were more reliable when 2% NaCl was added, tests with the two drug combinations were only minimally improved by adding 2% NaCl to the broth medium.


[Estrogens and brain].
Recent data upon molecular mechanisms of pleiotropic action of estrogens in human brain is presented in the article. Given detailed descriptions of properties of classical and membrane bound estradiol receptors, that maintain gene expression regulation, modulation of neurotransmittent systems and signal cascade activation in neuronal cells. Data upon regional distribution of estradiol receptor subtypes in the brain, their participation in main cell population function control (including progenitor cells) is given. Special attention is paid to estrogen participation in neurogenesis, inflammation and apoptosis regulation in central nervous system; in the control of formation and functioning of cerebral vessels.


On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology.
Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or Soluplus®, is a relatively new copolymer and a promising carrier of amorphous solid dispersions. Knowledge on the inherent properties of Soluplus® (e.g. cloud points, critical micelle concentrations, and viscosity) in different conditions is relatively inadequate, and the application characteristics of Soluplus®-based solid dispersions made by microwave methods still need to be clarified. In the present investigation, the inherent properties of a Soluplus® carrier, including cloud points, critical micelle concentrations, and viscosity, were explored in different media and in altered conditions. Ibuprofen, a BCS class II non-steroidal anti-inflammatory drug, was selected to develop Soluplus®-based amorphous solid dispersions using the microwave-quench cooling (MQC) method. Scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Raman spectroscopy (RS), and Fourier transform infrared spectroscopy (FT-IR) were adopted to analyze amorphous properties and molecular interactions in ibuprofen/Soluplus® amorphous solid dispersions generated by MQC. Dissolution, dissolution extension, phase solubility, equilibrium solubility, and supersaturated crystallization inhibiting experiments were performed to elucidate the effects of Soluplus® on ibuprofen in solid dispersions. This research provides valuable information on the inherent properties of Soluplus® and presents a basic understanding of Soluplus® as a carrier of amorphous solid dispersions.


Overview of the lady beetle tribe Diomini (Coleoptera: Coccinellidae) and description of a new phytophagous, silk-spinning genus from Costa Rica that induces food bodies on leaves of Piper (Piperaceae).
A new genus of lady beetle, Moiradiomus gen. nov. (Coleoptera: Coccinellidae Latreille, 1807: Diomini Gordon, 1999 ), and four new species are described from Costa Rica, representing the first known occurrences of obligate phytophagous lady beetle species outside of the tribe Epilachnini Mulsant, 1846 (sens. Ślipiński 2007). The new species are described, illustrated and keyed, and their life histories discussed. Each species of Moiradiomus occurs on a separate species of Piper L., 1753 (Piperaceae Giseke, 1792), where the larva constructs a small silken tent between leaf veins and inside this shelter induces the production of food bodies, which are its exclusive source of food. Background information is provided on lady beetle trophic relations and other insect/Piper symbioses. The taxonomic history of Diomus Mulsant, 1850 and related species in the tribe Diomini is reviewed and existing errors in observation, interpretation, identification, and classification are corrected in order to provide a more meaningful context for understanding the new genus. The tribe Diomini is rediagnosed and recircumscribed to include Diomus, Decadiomus Chapin, 1933, Heterodiomus Brèthes, 1925, Dichaina Weise, 1923, Andrzej Ślipiński, 2007, and Moiradiomus. Magnodiomus Gordon, 1999 and Erratodiomus Gordon, 1999 are removed from Diomini and transferred to Hyperaspidini Costa, 1849, subtribe Selvadiina Gordon, 1985 stat. nov. Mimoscymnus Gordon, 1994 and Planorbata Gordon, 1994, originally described in Coccidulini Mulsant, 1846 are also transfered to Hyperaspidini and placed in Mimoscymnina subtribe nov. (type genus Mimoscymnus). The main morphological characters distinguishing Diomini and Hyperaspidini are described and illustrated. A key to genera of Diomini sensu novo is provided. The identification of the Australian Diomus species illustrated in Gordon's publication on North American lady beetles is corrected from D. pumilio Weise, 1885 to D. tenebricosus (Boheman, 1859), however specimens recently collected in California do not match these genitalic illustrations and are identified as true D. pumilio. The following species of Diomus are transferred to Decadiomus as new combinations: D. balteatus (LeConte, 1878), D. floridanus (Mulsant, 1850), D. amabilis (LeConte, 1852), D. liebecki (Horn, 1895), D. myrmidon (Mulsant, 1850), D. humilis (Gordon, 1976), D. pseudotaedatus (Gordon, 1976), D. taedatus (Fall, 1901), D. bigemmeus (Horn, 1895), and D. austrinus (Gordon, 1976). Decadiomus seini Segarra, 2014 is placed as a junior synonym of D. austrinus. The following new species of Moiradiomus are described: M. clotho sp. nov., M. lachesis sp. nov., M. atopos sp. nov., M. nanita sp. nov.


Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993-2003).
To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment. Retrospective case series. 139 dogs with histologically confirmed nasal carcinomas. Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model. Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days). The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.


[Selective hematoporphyrin derivative (HMD) application in arterial vessels using a porous balloon catheter results in equivalent levels as compared to high-dose systemic administration].
The treatment of atherosclerotic vascular stenosis with percutaneous angioplasty is limited by a rate of restenosis of about 20-40%, in spite of new angioplasty devices. Histological and immune histological examinations of restenosed material obtained by coronary atherectomy indicate that cellular proliferation is an important determinant of restenosis. With the use of photodynamic therapy (PDT), it might be possible to selectively impair proliferating tissue by the application of the photosensitizer Photofrin II (a hematoporphyrin-derivative, HPD) followed by localized laser-light radiation. With the knowledge of the success of PDT in tumor therapy, the extension of the application of PDT in prophylaxis of restenosis should be examined. The technique used up to now works with the systemic application of the sensitizer. By applying HPD locally, however, one might be able to reduce the amount of the photosensitizer, but still achieve an equally cytotoxic effect. A recently developed catheter with a porous balloon enables local application of HPD. The following study describes the uptake and distribution of the hematoporphyrin-derivative Photofrin II within the walls of elastic and muscular type vessels after systemic and selective application. In 20 rabbits and seven pigs, Photofrin II was applied systemically (5 mg/kg i.v.) and locally (5 ml of 2.5 mg/ml). From each animal 12 vascular specimens (six arterial segments of either muscular and elastic type) were removed at a definite time within a defined period of 5 min to 24 h after application. To quantify the uptake of Photofrin II, we used fluorescence microscopy with digital image processing. After systemic application there was an increase of Photofrin II over a 4-h period. In contrast, a maximum concentration of Photofrin II was measured immediately after local application and found to be decreasing over a period of 4 h. The intima showed the highest uptake of HPD, both after local and systemic applications, as compared to uptake by the media and adventitia. The intimal uptake was significantly higher after local than after systemic application. Media and the adventitia showed, respectively, only one-half and one-fifth of the intima's intake. The rapid increase of the HPD concentration after local application would make PDT feasible in restenosis prophylaxis immediately after angioplasty without systemic side-effects of the photosensitizer.


[Depressive disorders in Parkinson's disease: clinical presentations, diagnosis, treatment].
An aim of the study was to investigate the psychopathological structure, pathopsychological mechanisms of the formation and predictors of depressive disorders in Parkinson's disease (PD), taking into consideration the form, stage, progression rate and severity of motor symptoms, and to develop a system of differential therapy. Along with general clinical and psychopathological examination, a complex of psychometric and psychodiagnostic methods was used. Three variants of depressive disorders were singled out: adaptation disorder (59 patients), prolonged depressive reaction; recurrent depressive disorder (36 patients), organic depressive disorder (89 patients). In total, 184 PD patients with depression disorders and 76 patients without depression were studied. History of disease, results of the clinical examination and changes in scores of psychometric and psychodiagnostic measurements as well as the results of differential pharmaco- and psychotherapy were considered for all variants.


Amnesic sensitivity to proactive interference: its relationship to priming and the causes of amnesia.
A group of alcoholic amnesics was compared with a group of controls on an A-B, A-C word pairs interference paradigm. With memory instructions the amnesics needed 5 presentation trials to their controls' single trials to match the groups on A-B cued recall. Under these conditions they still showed more proactive interference on the A-C list. When both groups were given five presentation trials for each list and 'free association' instructions, then they both showed this level of interference. This suggested that the amnesic interference effect only occurs because priming is not modulated by conscious memory, i.e. it is an effect of poor conscious memory. This interpretation was further supported by the finding that amnesics forgot the A-B list faster over 2 hr than their controls, when memory instructions were given.


Temporal variability in arctic fox diet as reflected in stable-carbon isotopes; the importance of sea ice.
Consumption of marine foods by terrestrial predators can lead to increased predator densities, potentially impacting their terrestrial resources. For arctic foxes (Alopex lagopus), access to such marine foods in winter depends on sea ice, which is threatened by global climate change. To quantify the importance of marine foods (seal carrion and seal pups) and document temporal variation in arctic fox diet I measured the ratios of the stable isotopes of carbon ((13)C/(12)C) in hair of arctic foxes near Cape Churchill, Manitoba, from 1994 to 1997. These hair samples were compared to the stable carbon isotope ratios of several prey species. Isotopic differences between seasonally dimorphic pelage types indicated a diet with a greater marine content in winter when sea ice provided access to seal carrion. Annual variation in arctic fox diet in both summer and winter was correlated with lemming abundance. Marine food sources became much more important in winters with low lemming populations, accounting for nearly half of the winter protein intake following a lemming decline. Potential alternative summer foods with isotopic signatures differing from lemmings included goose eggs and caribou, but these were unavailable in winter. Reliance on marine food sources in winter during periods of low lemming density demonstrates the importance of the sea ice as a potential habitat for this arctic fox population and suggests that a continued decline in sea ice extent will disrupt an important link between the marine and terrestrial ecosystems.


Immunization of mice with human immunodeficiency virus glycoprotein gp160 peptide 315-329 induces both class I- and class II-restricted T cells: not all T cells can respond to whole molecule stimulation.
The V3 loop of human immunodeficiency virus (HIV) glycoprotein gp160 is of interest as a possible site for protective immune responses. This article examines the murine T cell response to peptide 315-329 derived from HIV gp160. Surprisingly, immunization with peptide in complete Freund's adjuvant induced class I-restricted T cells as well as class II-restricted T cells. These data suggest that this peptide may have the unusual ability to enter the class I antigen processing pathway. Strategies that employ V3 loop peptides to induce protective immunity must generate T cells that can recognize epitopes derived from whole molecules in vivo. Therefore, peptide-induced T cells were tested for their ability to respond to naturally processed forms of gp120 and gp160 whole-molecule preparations. Peptide induced class I-restricted cells were capable of recognizing transfectants expressing gp160. However, only one of two class II-restricted T cell lines was capable of recognizing soluble whole molecules. This indicates that peptide immunization induces T cells that recognize a class II-restricted determinant that is not generated during normal processing of whole molecules. We have also examined the response of peptide primed T cells to lipidated peptide antigens. Lipidated peptides are generally considered to have increased antigenicity and immunogenicity as compared to normal peptides. However, lipidation of peptide 315-329 damaged both the class I- and II-restricted determinants, indicating that lipidation is not always desirable. The data presented here highlight a potential serious problem in the use of peptide vaccines, in that peptide immunization may not always induce T cells that can protect against a viral challenge.


Effects of anaesthetics and anticonvulsants on the action of kainic acid in the rat hippocampus.
The effects of anaesthetics and anticonvulsants on the acute behavioral response and neurochemical alterations following intrahippocampal injection of kainic acid were examined. When compared to the effects in animals anaesthetized with a combination of chloral hydrate and pentobarbital (Equithesin), brief anaesthesia with ether or with hexobarbital potentiated whereas prolonged anaesthetia attenuated the action of 0.5 microgram of kainic acid. Of the constituents of Equithesin, chloral hydrate offered less protection than pentobarbital. The anticonvulsants, phenobarbital, diazepam, diphenylhydantoin, and carbamazepine offered partial protection when administered in conjunction with ether anaesthetia.


Recurrent PDL1 expression and PDL1 (CD274) copy number alterations in breast implant-associated anaplastic large cell lymphomas.
Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a variant of anaplastic large cell lymphoma arising within seroma effusion associated with breast implants. BI-ALCL is a rare disease, recently recognized as a new provisional entity by the 2017 revised World Health Organization classification. All BI-ALCLs tested so far showed a "triple-negative" genetic profile-negative for ALK, DUSP22, and TP63 rearrangements-and were characterized by mutational and gene expression profiles consistent with aberrant activation of the JAK/STAT pathway. The active form of STAT3 (pSTAT3) is constantly expressed in BI-ALCLs and may favor tumor immune escape by triggering the transcription of PDL1 (CD274), a gene encoding the immune-checkpoint molecule programmed cell death ligand 1 (PDL1); immunohistochemical positivity for PDL1 has been recently described in 3 BI-ALCL cases, and one of them also harbored PDL1 gene amplification. We evaluated PDL1 and pSTAT expression by immunohistochemistry and PDL1 copy number alterations (CNAs) at chromosome 9p24.1 by fluorescent in situ hybridization in a cohort of 9 BI-ALCL cases; we also investigated the presence of tumor-infiltrating programmed cell death 1 (PD1)+ T cells (tumor-infiltrating lymphocytes, or TILs) and PDL1+ tumor-associated macrophages (TAMs) in BI-ALCL microenvironment. Tumor cells expressed PDL1 in 5 (56%) of 9 cases and harbored PDL1 CNAs in 3 (33%) of 9 cases; immunohistochemistry for pSTAT3 was positive in all 6 cases tested (100%), indicative of active JAK/STAT signaling. We observed PDL1 CNAs only among PDL1-positive cases, whereas PD1+ TILs and PDL1+ TAMs were present at variable levels in both PDL1-positive and PDL1-negative BI-ALCLs. We report frequent PDL1 expression and recurrent PDL1 CNAs in BI-ALCLs: our data suggest that 9p24.1 alterations represent a common mechanism of PDL1 overexpression in this disease, likely acting in synergy with constitutive pSTAT3 signaling. In PDL1-positive cases without chromosomal aberration, PDL1 expression may be induced by JAK/STAT signaling alone and/or others alternative pathways. BI-ALCL microenvironment hosts variable amounts of PD1+ TILs and PDL1+ TAMs, suggesting the presence of an active PD1/PDL1 axis. These findings may be of therapeutic value in advanced-stage patients who may benefit from a PD1/PDL1 blocking treatment.


Occurrence of moulds from bee pollen in Central Italy--A preliminary study.
The present study aimed to preliminary evaluate the occurrence of fungi in 40 specimens of trapped pollen collected from April-September 2015 in 40 apiaries from Tuscany (Central Italy). Cultural and microscopical examinations allowed the recognition of Cladosporium sp., Alternaria sp., Humicola sp. Mucoraceae and Acremonium sp. Penicillium brevicompactum, Penicillium chrysogenum, Aspergillus flavus , Aspergillus nidulans, Aspergillus niger and Aspergillus terreus were also identified. Yeasts and Fusarium spp. were not isolated. All pollen specimens were positive for at least one fungal isolate. Total CFU per gram ranged from 4-568. Aspergillus and Penicillium were obtained from 8 (20%) and from 22 (55%) pollen samples, respectively, associated in 4 cases (10%). The recovery of storage fungi such as Aspergillus and Penicillium in trapped pollen presents a potential risk for human health and attention should be paid to all stages of the post-harvest process.


The analysis of nickel refinery slimes and residues.
Procedures are outlined for the determination of the 28 elements usually present in the slimes and residues from nickel refineries.


Assessing the impact of the All-Wales Mental Handicap Strategy: a survey of four districts.
The All-Wales Mental Handicap Strategy (AWS) pledged government leadership and additional resources for the task of developing community based residential, domiciliary, respite, daycare and professional services for people with mental handicaps and their families throughout Wales. Ultimately, the authors of the AWS sought to affect for the better the extent to which people with mental handicaps experience typical community life. A large random sample of people with mental handicaps in four diverse districts was used to track changes in services received, professional input, involvement in individual planning, the number of community activities pursued, and the size and range of individuals' social networks across the middle 4 years of the AWS. The balance between private housing and service residence remained unchanged although, with the ageing of the cohort, there was a decrease in the proportion living with parents and an increase in those living independently or in another family situation. There was an increase in the availability of residential services in the form of ordinary housing and an associated contraction in large congregate care facilities. However, not all moves were towards more ordinary living. Some people moved from large statutory sector specialist facilities to other atypical forms of residence, as did some people from family homes. Family support services in the form of family aides and short-term care increased significantly, but indicators still suggest that an expansion of these services is merited. Day services diversified slightly, but without affecting the major role of the traditional centre. There was a decrease in the numbers receiving a fulltime service. Only a third of the sample received regular individual plan reviews of the services they received and the developmental goals set in their name. In general, individuals were involved in a greater number of community activities that brought them into contact with other citizens. However, such an increase has not led to significant changes in the size or composition of people's friendship networks. Overall, the changes in service provision and family and user experience have been in line with the direction set by the AWS. However, the degree of change still required before the new pattern of services envisaged by the AWS is substantially in existence, or the experience of people with mental handicaps conforms with the guiding principles which underpin it, is considerably greater than that achieved after 7 of its initial 10 years.


Temperature dependence of binding and catalysis for human serum arylesterase/paraoxonase.
The influence of temperature upon the hydrolysis of phenyl acetate, catalysed by purified human serum arylesterase/paraoxonase (E. C. 3.1.8.1), was studied in the temperature range 10 °C-40 °C by spectrophotometry in TRIS buffer, pH 8.0, using both initial rate analysis and progress curve analysis. The kinetic parameters (catalytic constant k(cat); Michaelis constant K(m); product inhibition constant K(p)) were determined by nonlinear regression. All parameters increased with temperature, but the ratios k(cat)/K(m) and K(p)/K(m) remained practically constant. Binding of both substrate and reaction product (phenol) was exothermic. A negative entropic term accounted for about 50% of the enthalpy change for both the binding and catalytic steps. Thermodynamic analysis suggested that: (1) the rate-limiting step is the nucleophilic attack of the carbonyl group of the substrate by a water molecule, (2) the active site is preorganized with no induced fit, (3) the enzyme-bound calcium plays an important role in stabilizing both the substrate and the transition state. The practical implications of these results are discussed.


Identification of AcMNPV EXON0 (ac141) domains required for efficient production of budded virus, dimerization and association with BV/ODV-C42 and FP25.
The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) late gene exon0 (ac141) is required for the efficient production of budded virus (BV). EXON0 interacts with nucleopcapsid protein BV/ODV-C42 and FP25 and enables egress of nucleocapsids from the nucleus to the cytoplasm. This study examines the functional domains of EXON0 that play a role in BV production. Six putative domains of the 261 amino acid EXON0 were deleted and examined for functionality by determining their ability to rescue an AcMNPV exon0 knockout bacmid. Domain mapping results showed that all the six domains were required but deletion of the N-terminal acidic region and the leucine zipper domains had the greatest impact on BV production. Yeast 2-hybrid and co-immunoprecipitation demonstrated that EXON0 formed dimers. Point mutation analysis demonstrated that the leucine zipper was required for dimer formation and interaction with BV/ODV-C42 and FP25. The charged domain was also required for BV/ODV-C42 interaction.


The effects of cell density, attachment substratum and dexamethasone on spontaneous apoptosis of rat hepatocytes in primary culture.
The rates of spontaneous cell detachment, cell viability, and apoptosis in primary cultures of rat hepatocytes plated at high and low density were compared. Apoptosis was frequent in detached cells, and the rates of cell detachment and apoptosis were greater in high-density than in low-density cultures. Among attached cells, more cells had condensed or fragmented nuclei in high-density than in low-density cultures. Further, ladder-like DNA fragmentation was not seen in low-cell-density cultures but was clearly evident in high-density cultures. Bax was more highly expressed in cells cultured at high density, and on collagen vs. matrigel, whereas changes of Bcl-2 and Fas expression observed in culture appeared unrelated to the rate of apoptosis. The rate of hepatocyte apoptosis appeared to be identical in low-density cultures on collagen 1 and matrigel, but when cells were cultured at high density, matrigel suppressed apoptosis by more than 50% at 36 h. In hepatocytes cultured on collagen 1, dexamethasone (0.1 microM) suppressed apoptosis in both low- and high-density cultures; higher doses had no further effects. In high density cultures, aurintricarboxylic acid (10 microM) suppressed apoptosis and this improved cell attachment at 48 h. It is concluded that cell viability in primary cultures of rat hepatocytes grown on collagen I is dependent on optimal culture density and that the cell population is regulated, at least in part, by apoptosis. Corticosteroids suppress spontaneous apoptosis of cultured hepatocytes in a non-dose-dependent manner, whereas matrigel abolishes apoptosis induced by increasing cell density. Bax may be an important protein in the cell density and cell matrix-dependent regulation of apoptosis in cultured hepatocytes.


Reconsideration of the primary and secondary diagnostic criteria of Meckel's diverticulum scintigraphy. A study of 93 confirmed cases.
Meckel's diverticulum scintigraphy (MDS) is a common method for diagnosing ectopic gastric mucosa (EGM), but atypical images are difficult to diagnose. This study aimed to improve the understanding of the existing diagnostic criteria through a review of confirmed cases. A total of 352 patients underwent MDS. Among 120 patients with a positive diagnosis, 106 underwent surgery. This study analyzed the imaging presentation, surgical records, and pathological results. The existing diagnostic criteria included the location, shape, and radioactive appearance of the lesions. Data from surgical records with typical or atypical images were compared. One hundred cases (100/106) were surgically confirmed to be Meckel's diverticulum (MD). The remaining 6 were intestinal polyps, intestinal duplication, duodenal ulcer, non-Hodgkin's lymphoma (NHL) and hiatal hernia. Out of the 100 MD cases, 93 had complete operation records and 59/93 of the MDS 63.4% MD were located in the right lower quadrant, and 81.7% had a round shape in the scintiscan. The onset of the lesions activity in 96.8% (90/93) of the cases corresponded with the onset of the gastric activity. The radioactivity of 97.8% (91/93) of the lesions gradually increased during the examination. There were no significant differences between the typical and atypical scintiscan images: in the distance of MD from the ileocecal valve, in the MD length, and the basal diameter of MD for lesions at different scintiscans (P>0.05), or of different shapes (P>0.05). Location in the right lower quadrant and round shape of the lesions are not the primary diagnostic factors for Meckel's diverticulum. The establishment of the diagnosis of MD requires careful consideration of other imaging characteristics such as: a) The onset of lesions' radioactivity to correspond with the onset of the gastric activity and b) The lesions' radioactivity to gradually increase during the scan procedure.