Ethical issues in solid organ transplantation: transfusion-free transplantation in Jehovah's witness patients.
Jehovah's Witnesses do not accept transfusion of major allogeneic blood fractions. Successful solid organ transplantation is challenging for Jehovah's Witnesses when anemia, coagulation disturbances, and difficult technical aspects co-exist, and key blood bank resources cannot be utilized. Organ availability for transplantation is limited and demand exceeds supply for all organ types. Historically, the likelihood of poor outcomes in Jehovah's Witnesses patients placed ethical limitations on transplant candidacy for this population violating the precept of maximal utilization of a limited resource. The review's purpose is to describe advancements and strategies that make Jehovah's Witnesses transplant outcomes comparable to transfusion-eligible patients and allay the ethical concerns of their candidacy. Immunomodulation from allogeneic transfusion is a cause of significant postop morbidity. Blood conservation strategies have led to improved outcomes across different medical and surgical cohorts and set the stage for expanded utility in Jehovah's Witnesses with organ insufficiency.Published single-center series with descriptions of specific peri-operative strategies describe the path to major blood product avoidance. Comparable outcomes in solid organ transplantation for Jehovah's Witnesses without allogeneic transfusion are possible when inclusion-exclusion criteria are respected, and blood conservation strategies employed.


Interleukin-1beta is a negative transcriptional regulator of alpha1-adrenergic induced gene expression in cultured cardiac myocytes.
We recently reported that interleukin-1beta (IL-1beta) induces a novel form of cardiac myocyte hypertrophy characterized by an increase in protein content but an absence of the fetal program of skeletal alpha-actin or beta-myosin heavy chain (beta-MHC) gene expression (Palmer, J. N., Hartogensis, W. E., Patten, M., Fortuin, F. D., and Long, C. S. (1995) J. Clin. Invest. 95, 2555-2564). Because of the apparent disparity between this myocardial phenotype and that seen with other hypertrophic agents in culture, such as catecholamines, we investigated the effect of IL-1beta on alpha1-induced cardiomyocyte hypertrophy. Although there was no augmentation in total protein when IL-1beta and phenylephrine were given simultaneously, IL-1beta attenuated the increase in contractile protein mRNAs (skeletal alpha-actin and beta-MHC) in response to phenylephrine. Transient transfection studies with skeletal alpha-actin and beta-MHC promoter constructs linked to the chloramphenicol acetyltransferase (CAT)-reporter gene indicate that repression occurred at the level of gene transcription. In view of the previously reported activity of the zinc finger protein YY1 in the negative regulation of the skeletal alpha-actin promoter in cardiomyocytes (MacLellan, W. R., Lee, T. C., Schwartz, R. J., and Schneider, M. D. (1994) J. Biol. Chem. 269, 16754-16760), we investigated the potential role of this factor in the IL-1beta-mediated effects. Using transient transfection, we found that a mutation in the YY1 binding site of the skeletal alpha-actin promoter abolished the inhibitory effect of IL-1beta. We further found that the 127-base pair fragment of the skeletal alpha-actin promoter required for the IL-1beta effect is also required for inhibition by the overexpression of YY1 in the myocytes. Furthermore, increased levels of YY1 protein are found in IL-1beta treated myocytes. Taken together these results suggest that the repression of contractile protein gene transcription by IL-1beta may be due, at least in part, to activation of the negative transcription factor YY1.


Varying protein and starch in the diet of dairy cows. II. Effects on performance and nitrogen utilization for milk production.
The main objective of this experiment was to examine the effects of the percentage and source of crude protein (CP) and the amount of starch in the diet of dairy cows on the lactational performance and use of N for milk production. Sixty multiparous Holstein cows were used in a 210-d lactational trial with a completely randomized design with a 2 x 3 factorial arrangement of treatments. Two sources of CP [solvent-extracted soybean meal (SBM) and a mixture of SBM and a blend of animal-marine protein supplements plus ruminally protected Met (AMB)] and 3 levels of dietary CP (means = 14.8, 16.8, and 18.7%) were combined into 6 treatments. On a dry matter (DM) basis, diets contained 25.0% corn silage, 20.0% alfalfa silage, 10.0% cottonseed, 26.7 to 37.0% corn grain, and 4.8 to 13.5% protein supplement, plus minerals and vitamins. Across the 210 d of lactation, the productive response of dairy cows to the source of supplemental CP depended on the concentration of CP in the diet. At 18.7% CP, cows fed SBM consumed more DM and produced more milk, 3.5% fat-corrected milk, fat, and true protein, but had lower efficiency of feed use and body condition score than cows fed AMB. At 16.8% CP, cows fed AMB produced more 3.5% fat-corrected milk, fat, and true protein than cows fed SBM. At 14.8% CP, cows fed SBM consumed more DM but produced less true protein and had lower feed efficiency than cows fed AMB. Across CP sources, cows fed 14.8% CP produced less fat-corrected milk and true protein than cows fed 16.8 and 18.7% CP. Across CP percentages, cows fed AMB produced more fat-corrected milk per kilogram of DM consumed than cows fed SBM. Despite these interactions, improvements in the gross efficiency of N use for milk production were achieved through reductions in the intake of N independently of the source of CP. Data suggest that the intake of N by high-producing dairy cows that consume sufficient energy and other nutrients to meet their requirements can be decreased to about 600 to 650 g daily if the source of RDP and RUP are properly matched with the source and amount of carbohydrate in the diet.


Thrombotic risk minimization for Diane-35 and generics.
This study aimed to evaluate the effect of risk minimization measures on cyproterone acetate/ethinylestradiol (CPA/EE) use in the Netherlands. Potential indications of use and concomitant pharmacy dispensing of other hormonal contraceptives (HC) were assessed among new users in 2011, 2012, and 2014. In this retrospective drug utilization study, new CPA/EE users were identified by pharmacy dispensings in the PHARMO Database Network in 2011, 2012, and 2014. Recent dispensing of drugs to treat acne and concomitant dispensing of other HC were also assessed. General practitioner records were linked to identify diagnoses of acne, other hyperandrogenic conditions, menstrual problems, or consultations for contraceptive management in the preceding year. The number of new CPA/EE users identified per year was 7876 in 2011 and 7562 in 2012 (3.7 new users per 1000 women in both years) and 1401 in 2014 (0.7 per 1000 women). The proportions of users with acne diagnosis or treatment were 55% in 2011, 52% in 2012, and 47% in 2014. Concomitant use of other HC was observed for 3% of new CPA/EE users in 2011, and 2% in 2012 and 2014 (median duration 78 days). Another 25% were potential concomitant users (median duration 60 days). This descriptive analysis showed similar proportions of CPA/EE users examined with acne or other hyperandrogenic conditions, or with recent acne treatment, or concomitant dispensing of other HC in the Netherlands before and after the referral procedure. The key observation was a strong overall reduction of CPA/EE use in the Netherlands.


Distal femoral cortical hypertrophy: predisposing factors and their effect on clinical outcome.
The clinical and radiographic features of 109 hybrid total hip replacements performed between 1986 and 1992 in 96 consecutive patients were retrospectively reviewed. A cementless Harris-Galante (HGP1) cup and a 32 mm monobloc straight Muller stem were used in all cases. The overall prevalence of distal femoral cortical hypertrophy (DCH) was 43.1%. Male sex, underlying diagnosis of avascular necrosis and Charnley grade A were among the factors that predisposed to the development of DCH. The prevalence of stem radiolucencies was lower in the group of patients who developed DCH compared with those without hypertrophy. The Harris Hip Score ranged between 5 and 54 preoperatively and the average HHS was more than 80 postoperatively. No association was found between DCH and thigh pain.


A survey of 4478 biopsy specimens of oral lesions.
A surgery of 4478 biopsy specimens in dental institute in India was carried out to compare and correlate results obtained from such studies carried out elsewhere. The study revealed that there are more than 150 common and rare oral diseases which are diagnosed and treated by dentists. 13 common diseases comprised majority (60.37%) of the biopsy specimens studied. Of these, tumors (25.53%) and Cysts (14.38%) constituted the majority of the bulk. The study also shows that most of the benign tumors were mesenchymal in origin (almost 5.5:1) while malignant tumors were epithelial (almost 20:1) in origin. Cystic lesions included the most common radicular cyst (7.12%) and the rare hydatid cyst (one case reported). Gingival hyperplasia mainly due to local aetiology, constituted the 3rd largest group. The purpose of this report is to provide some information about the type and frequency of oral lesions usually diagnosed, with the help of histopathological examination in India.


No effect of the plant growth regulator, chlormequat, on boar fertility.
Chlormequat is a commonly used plant growth regulator in agriculture. Defined levels of chlormequat residue are allowed in food and an acceptable daily intake is defined for humans. However, there are results in the literature suggesting that a daily intake below the acceptable level for human is detrimental for mammalian reproduction. In the present experiment we investigated the effect of chlormequat at levels up to that acceptable for humans on reproduction in male pigs. Chlormequat (also known as chlorocholine chloride (CCC)) was mixed into the diet and given to the experimental animals at three levels (three treatment groups), i.e. 0 mg CCC/kg BW per day (Control), 0.025 mg CCC/kg BW per day and 0.05 mg CCC/kg BW per day. Eight mother sows per treatment group were used in the experiment. From the day of insemination, the mother sows received the experimental diets. The piglets were weaned at 4 weeks of age and two boar littermates continued on the same treatment as the dam until maturity and delivery of semen for in vitro fertilization (IVF) and in vivo fertilization. Semen volume, sperm concentration and fraction of live sperms were not (P 0.46) detrimentally affected by chlormequat intake. The fraction of oocytes developing to more than the one-cell stage at day 5 after IVF was not (P = 0.88) detrimentally affected by chlormequat intake. Chlormequat intake did not detrimentally affect the fraction of gilts being pregnant after one insemination (P = 0.65) or the number of embryos in the pregnant gilts (P = 0.36). Serum chlormequat concentration was 0.9 μg/kg in the 0.025 mg CCC/kg BW per day group and 1.8 μg/kg in the 0.05 mg CCC/kg BW per day group, but was below the detection limit in control animals. In conclusion, the plant growth regulator chlormequat could not be proven to be detrimental to the selected reproduction traits in male pigs. This is in contrast to existing results from the male mouse.


The burden of injuries according to maturity status and timing: A two-decade study with 110 growth curves in an elite football academy.
Injuries have a negative impact on the development of football players. Maturation is a potential risk factor for football injuries but available data on this topic provide limited evidence due to methodological shortcomings. The aim of this study was to describe the injury burden of male academy football players according to growth curve-derived maturity status and timing. Injury and growth data were collected from 2000 to 2020. Longitudinal height records for 110 individual players were fitted with the Super-Imposition by Translation and Rotation model to estimate age at peak height velocity (PHV). Players were clustered according to maturity status (pre-, circa-, post-PHV, or adults) and timing (early, on-time, late maturers). Overall and specific injury burdens (days lost/player-season) and rate ratios for comparisons between groups were calculated. Overall injury burden increased with advanced maturity status; pre-PHV players had 3.2-, 3.7-, and 5.5-times lower burden compared with circa-PHV, post-PHV, and adult players, respectively. Growth-related injuries were more burdensome circa-PHV, while muscle and joint/ligament injuries had a higher impact post-PHV and in adults. Further, in the pre-PHV period, late maturers showed lower burden of overall, growth-related, anterior inferior iliac spine osteochondrosis, and knee joint/ligament injuries compared with on-time maturers. In adult players, however, injuries were less burdensome for early maturers than on-time and late maturers. In addition, joint/ligament injuries of adult late maturers were 4.5-times more burdensome than those of early maturers. Therefore, monitoring maturity seems crucial to define each player's maturation profile and facilitate design of targeted injury prevention programmes.Highlights Injury burden is significantly lower in football players at pre-peak height velocity (PHV). Growth-related injuries are most burdensome circa-PHV, while muscle and joint/ligament injuries are more burdensome post-PHV and especially in adults.Before PHV, growth-related and knee joint/ligament injuries have lower burden in players who mature late than those who mature on-time. Adult late maturers have greater burden of overall and joint/ligament injuries than early maturers.Football academies should regularly assess the maturity status and timing of young football players, as the impact of injuries varies with maturation status and timing.Management of the maturity-related injury risk profile, in combination with other relevant factors (training load, neuromuscular and biomechanical factors, physiotherapy, coaching, communication, psychosocial factors …), might help improve the success of player development programmes and protect the health of young football players.


Neuroprotective effects of hyperbaric oxygen treatment on traumatic brain injury in the rat.
This study was designed to evaluate the potential benefits of hyperbaric oxygen (HBO) in the treatment of traumatic brain injury (TBI). The right cerebral cortex of rats was injured by the impact of a 20-g object dropped from a predetermined height. The rats received HBO treatment at 3 ATA for 60 min after TBI. Neurological behavior score, brain water content, neuronal loss in the hippocampus, and cell apoptosis in brain tissue surrounding the primary injury site were examined to determine brain damage severity. Three and six hours after TBI, HBO-treated rats displayed a significant reduction in brain damage. However, by 12 h after TBI, the efficacy of HBO treatment was considerably attenuated. Furthermore, at 24, 48, and 72 h after TBI, the HBO treatment did not show any notable effects. In contrast, multiple HBO treatments (three or five times in all), even when started 48 h after TBI, remarkably reduced neurology deficit scores and the loss of neuronal numbers in the hippocampus. Although multiple treatments started at 48 h significantly improved neurological behaviors and reduced brain injury, the overall beneficial effects were substantially weaker than those seen after a single treatment at 6 h. These results suggest that: (1) HBO treatment could alleviate brain damage after TBI; (2) a single treatment with HBO has a time limitation of 12 h post-TBI; and (3) multiple HBO treatments have the possibility to extend the post-TBI delivery time window. Therefore, our results clearly suggest the validity of HBO therapy for the treatment of TBI.


Maternal mortality at the State Specialist Hospital Bauchi, Northern Nigeria.
To analyse and document our experiences with maternal mortality with the view of finding the trends over the last seven years, common causes and attributing socio-demographic factors. A prospective analysis of maternal mortality. State Specialists Hospital Bauchi, Bauchi Northeastern Nigeria. These include maternal mortality ratio for the period under review and the annual trends, age and parity most affected the direct and indirect causes of maternal mortality in our environment. The Maternal Mortality Ratio (MMR) for the period under review was 1,732 per 100, 000 live births. Six hundred and twenty one of the deaths (81.0%) occurred in 12,067 unbooked deliveries giving a maternal mortality ratio of 5,146 per 100,000 for unbooked mothers. This ratio is approximately eleven times that obtained in booked live deliveries. Age range was 14-44 years and the mean age was 27.8 years. The highest maternal death was in the adolescent mothers. The primigravidas had the highest maternal mortality of 28.9%. The direct obstetric causes of maternal death accounted for 79.4% of the deaths. The major causes of deaths were eclampsia 31.9%, haemorrhage 19.2% and sepsis 10.4%. Amongst the indirect causes of maternal death, anaemia was the leading cause accounting for 12.1%. The annual MMR was highest for the year 2006 (2,586 per 100,000). Maternal mortality is unacceptably high in our environment. The provision of more health facilities where basic and comprehensive antenatal care are provided, skilled attendants at birth, community mobilisation to improve antenatal attendance and the use of TBAs as a link between the pregnant women, families and communities providing important messages for a healthy pregnancy, and safe birth remain the bedrock of containing maternal mortality in our environment.


Single-stage interpolation flaps in facial reconstruction.
Relatively deep and complex surgical defects, particularly when adjacent to or involving free margins, present significant reconstructive challenges. When the use of local flaps is precluded by native anatomic restrictions, interpolation flaps may be modified to address these difficult wounds in a single operative session. To provide a framework to approach difficult soft tissue defects arising near or involving free margins and to demonstrate appropriate design and execution of single-stage interpolation flaps for reconstruction of these wounds. Examination of our utilization of these flaps based on an anatomic region and surgical approach. A region-based demonstration of flap conceptualization, design, and execution is provided. Tunneled, transposed, and deepithelialized variations of single-stage interpolation flaps provide versatile options for reconstruction of a variety of defects encroaching on or involving free margins. The inherently robust vascularity of these flaps supports importation of necessary tissue bulk while allowing aggressive contouring to restore an intricate native topography. Critical flap design allows access to distant tissue reservoirs and placement of favorable incision lines while preserving the inherent advantages of a single operative procedure.


Evidence from serial sections that some cells contain large numbers of mitochondria.
Three-dimensional reconstructions based on serial sections through cells of the chloromonadophycean alga Gonyostomum semen Diesing indicate that there are many small unbranched mitochondria in log-phase cells. These organelles are approximately ellipsoid in shape with their longest axis ranging from 0-7 to 2-0 micrometer in length. Occasionally mitochondria reaching up to 3-6 micrometer in length have been observed: these have the same general morphology as their smaller counterparts. Preliminary observations indicate that cells of a related alga, Vacuolaria virescens Cienkowsky, also possess many small unbranched mitochondria. These observations are discussed in relation to recent reports that some cells contain a single branched mitochondrion or, at most, a small number of these organelles. It is suggested that mitochondrial number may be related to cell volume and that large cells may contain many mitochondria.


Rapid evolution of silver nanoparticle resistance in Escherichia coli.
The recent exponential increase in the use of engineered nanoparticles (eNPs) means both greater intentional and unintentional exposure of eNPs to microbes. Intentional use includes the use of eNPs as biocides. Unintentional exposure results from the fact that eNPs are included in a variety of commercial products (paints, sunscreens, cosmetics). Many of these eNPs are composed of heavy metals or metal oxides such as silver, gold, zinc, titanium dioxide, and zinc oxide. It is thought that since metallic/metallic oxide NPs impact so many aspects of bacterial physiology that it will difficult for bacteria to evolve resistance to them. This study utilized laboratory experimental evolution to evolve silver nanoparticle (AgNP) resistance in the bacterium Escherichia coli (K-12 MG1655), a bacterium that does not harbor any known silver resistance elements. After 225 generations of exposure to the AgNP environment, the treatment populations demonstrated greater fitness vs. control strains as measured by optical density (OD) and colony forming units (CFU) in the presence of varying concentrations of 10 nm citrate-coated silver nanoparticles (AgNP) or silver nitrate (AgNO3). Genomic analysis shows that changes associated with AgNP resistance were already accumulating within the treatment populations by generation 100, and by generation 200 three mutations had swept to high frequency in the AgNP resistance stocks. This study indicates that despite previous claims to the contrary bacteria can easily evolve resistance to AgNPs, and this occurs by relatively simple genomic changes. These results indicate that care should be taken with regards to the use of eNPs as biocides as well as with regards to unintentional exposure of microbial communities to eNPs in waste products.


Dysregulated myelopoiesis and hematopoietic function following acute physiologic insult.
The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis. Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term functional status. Multiple approaches targeting MDSC expansion and suppressor cell activity may serve as a primary or adjunctive therapeutic intervention. Traumatic injury and the neuroendocrine stress response suppress bone marrow erythropoietin receptor expression in a process that may be reversed by nonselective beta-adrenergic receptor blockade. Hepcidin-mediated iron-restricted anemia of critical illness requires further investigation of novel approaches involving erythropoiesis-stimulating agents, iron administration, and hepcidin modulation. Emergency myelopoiesis is a dynamic process with unique phenotypes for different physiologic insults and host factors. Following an acute physiologic insult, critically ill patients are subject to persistent MDSC expansion, deterioration of lymphocyte number and function, and inadequate stress erythropoiesis. Better strategies are required to identify patients who are most likely to benefit from targeted therapies.


Ca2+ Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity.
Fusion with, and subsequent entry into, the host cell is one of the critical steps in the life cycle of enveloped viruses. For Middle East respiratory syndrome coronavirus (MERS-CoV), the spike (S) protein is the main determinant of viral entry. Proteolytic cleavage of the S protein exposes its fusion peptide (FP), which initiates the process of membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium ions (Ca2+) play an important role in fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FPs share a high sequence homology, and here, we investigated whether Ca2+ is required for MERS-CoV fusion by screening a mutant array in which E and D residues in the MERS-CoV FP were substituted with neutrally charged alanines (A). Upon verifying mutant cell surface expression and proteolytic cleavage, we tested their ability to mediate pseudoparticle (PP) infection of host cells in modulating Ca2+ environments. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV wild-type (WT) PP infection by approximately 2-fold and that E891 is a crucial residue for Ca2+ interaction. Subsequent electron spin resonance (ESR) experiments revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry showed an approximate 1:1 MERS-CoV FP to Ca2+ ratio, as opposed to an 1:2 SARS-CoV FP to Ca2+ ratio, suggesting significant differences in FP Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging infectious disease with zoonotic potential and has reservoirs in dromedary camels and bats. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans, with 2,468 confirmed cases causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. In order to develop novel drugs and vaccines, it is important to understand the molecular mechanisms that enable the virus to infect host cells. Our data have found that calcium is an important regulator of viral fusion by interacting with negatively charged residues in the MERS-CoV FP region. This information can guide therapeutic solutions to block this calcium interaction and also repurpose already approved drugs for this use for a fast response to MERS-CoV outbreaks.


The accuracy of urinary ultrasound in the diagnosis of urinary stone disease in patients with acute flank pain: is it influenced by the time of ultrasound performance during the day or week?
The aim of this article is to investigate the possible impact of timing of ultrasound (US) during the day or week on its diagnostic accuracy. We analyzed the records of 500 patients who underwent an initial urinary US, followed by a noncontrast computed tomography (NCCT) for the assessment of urinary stone disease. The sensitivity, specificity, negative and positive predictive values, negative and positive likelihood ratio, and overall diagnostic accuracy rates of US and were analyzed at different times of the day or week. The specificity and diagnostic accuracy of urinary US showed a decline toward the middle of the week followed by a steady rise by the end of the week, higher sensitivity for urinary US was noticed around mid-week. On the other hand, when urinary US results are subgrouped according to the time of the day they are performed, the specificity remained generally stable but the sensitivity and diagnostic accuracy showed lowest levels between 11:00 a.m. and 02:00 p.m. and between 04:00 p.m. and 05:00 p.m. Although some observational differences between sensitivity, specificity, and diagnostic accuracy of urinary US performed at different times of the day or week are seen, these differences were not statistically significant. Our study showed no significant influence of US timing on its diagnostic accuracy. A larger randomized prospective series is necessary to evaluate the impact of different factors on "precision" and "accuracy" in US reporting and, hence, the diagnostic accuracy of urinary US in identifying urinary stone disease.


Challenges, attitudes and practices of the spectacle wearers in a resource-limited economy.
To evaluate challenges, attitudes and practices among spectacle wearers to effect positive change when necessary, and determine positive change in a resource-limited economy. A multi-hospital descriptive, cross sectional survey of spectacle wearers was conducted between May 2007 and December 2008 in Nigeria. A total of 214 wearers comprising 43.5% males and 56.5% females aged 18-84 years were surveyed. The majority of subjects (92.6%) had at least secondary education. The wearers' challenges included expensive spectacles (43.0%), falling/scratched/broken lenses (29.4%) and fear that spectacles would damage the eyes (23.8%). The wearers' attitudes were comprised of consultations with 'road side dispensers' (7%) and permitting other individuals to select spectacle frames for them (26%). Care and maintaince practices included use of handkerchief, tissue paper, fingers and water to clean spectacles (49.5%) and placing spectacles inside spectacle cases (30.4%). There were no associations (P > 0.05) between gender or literacy levels and who selected the frames for the subjects, caregivers consulted for spectacles, and cleaning materials for spectacles. The placement of spectacles when not in use was significantly associated (P < 0.05) with the wearers' gender and literacy levels but not with the length of spectacle wear. Attitudes and practices requiring positive change crossed gender and educational levels among spectacle wearers. The cost of spectacles should be regulated and availability of standard eye care practices would reduce challenges including lens-related defects and quackery. During consultation with a recognized eye care professional, counseling of wearers on positive attitudes/practices as well as allaying fear of spectacle wear is required.


Mechanical thrombectomy in patients with acute cancer-related stroke: is the stent retriever alone effective?
The optimal first-line mechanical thrombectomy (MT) method in cancer-related stroke (CRS) patients with emergent large vessel occlusion (ELVO) remains largely unknown. The aim of this study is to evaluate the efficacy and safety between contact aspiration (CA) first-line thrombectomy and stent retriever (SR) first-line thrombectomy in CRS patients. Sixty-two CRS patients with ELVO, who underwent MT between January 2013 and October 2019 at our institution, were retrospectively analyzed. Patients were divided into two groups based on the first-line MT method and compared: the CA group (n=28), which included those who received CA alone or combined CA with SR, and the SR group (n=34), which included those who received conventional SR alone. Overall, reperfusion was successful in 75.8% (47/62) of CRS patients, and a good clinical outcome at 90 days was observed in 17.7%. The CA group showed a higher rate of successful reperfusion (89.3% vs 64.7%, P=0.025) shorter procedure time (22 vs 42 min; P=0.029), higher rate of first pass effect (35.7% vs 11.8%, P=0.025), and lower number of passes (1 vs 3, P=0.023) when compared with the SR group. The procedural and hemorrhagic complication rates were similar between the CA and SR groups. The first-line contact aspiration (OR 11.624, 95% CI 1.041 to 129.752; P=0.046) was an independent predictor of successful reperfusion. Among patients with CRS, CA - whether alone or in combination with SR - as first-line MT seems to provide more rapid and successful reperfusion when compared with SR.


Preparation of hydroxyapatite from animal bones.
This paper presents the method of obtaining hydroxyapatite from animal bones. Bone sludge and calcined products were characterized by X-ray diffraction (XRD), Fourier transformed infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Calcium concentration was determined with titration, and phosphorus--spectrophotometrically. Making use of the AAS and ICP methods the content of microelements was determined. In all the products, hydroxyapatite was the only crystalline phase indicated. The FT-IR spectra confirmed that calcination removed the total of organic substances. Calcium and phosphorus contents were 38% and 18%, respectively, which corresponded to the Ca/P molar ratio of nonstoichiometric hydroxyapatite. The specific surfaces of products were measured by BET method. The volume of micro- and mesopores was determined.


Practice patterns of image guided particle therapy in Europe: A 2016 survey of the European Particle Therapy Network (EPTN).
Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres. In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT. All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods. Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines.


The regulation of glycolysis in perfused locust flight muscle.
Concentrations of glycolytic intermediates, amino acids and possible regulator substances were measured in extracts from locust thoracic muscles perfused under different conditions. The conversion of [(14)C]glucose into intermediates and CO(2) by muscle preparations was also followed. When muscles perfused with glucose were made anaerobic changes in metabolite concentrations occurred that could be accounted for by an activation of phosphofructokinase and pyruvate kinase. When butyrate and glucose were present in the perfusion medium the rate of glycolytic flux was lower than with glucose alone, and the aldolase reaction appeared to be inhibited. When butyrate alone was supplied to the muscle the concentrations of most glycolytic intermediates were similar to those found when glucose was supplied. Iodoacetate caused changes in concentrations of intermediates that appeared to result from inhibition of glyceraldehyde 3-phosphate dehydrogenase. Fluoroacetate-poisoned muscles showed a high citrate concentration, but no obvious site of inhibition by citrate was apparent in the glycolytic pathway. Mechanisms for control of glycolysis in locust flight muscle are discussed and related to the known properties of isolated enzymes. It is proposed that trehalase, hexokinase, phosphofructokinase, aldolase, and pyruvate kinase may be control enzymes in this tissue.


Randomized, Double-Blind, Placebo-Controlled Study of Encenicline, an α7 Nicotinic Acetylcholine Receptor Agonist, as a Treatment for Cognitive Impairment in Schizophrenia.
Encenicline is a novel, selective α7 nicotinic acetylcholine receptor agonist in development for treating cognitive impairment in schizophrenia and Alzheimer's disease. A phase 2, double-blind, randomized, placebo-controlled, parallel-design, multinational study was conducted. Patients with schizophrenia on chronic stable atypical antipsychotics were randomized to encenicline 0.27 or 0.9 mg once daily or placebo for 12 weeks. The primary efficacy end point was the Overall Cognition Index (OCI) score from the CogState computerized battery. Secondary end points include MATRICS Consensus Cognitive Battery (MCCB) (in US patients), the Schizophrenia Cognition Rating Scale (SCoRS) total score, SCoRS global rating, and Positive and Negative Syndrome Scale (PANSS) total and subscale and cognition factor scores. Of 319 randomized patients, 317 were included in the safety population, and 307 were included in the intent-to-treat population. Notable trends in improvement were demonstrated across all cognition scales. For the OCI score, the LS mean difference for encenicline 0.27 mg vs placebo was significant (Cohen's d=0.257; P=0.034). Mean SCoRS total scores decreased showing improvement in function over time, and the difference was significant for encenicline 0.9 mg vs placebo (P=0.011). Furthermore, the difference between encenicline 0.9 mg and placebo was significant for the PANSS Cognition Impairment Domain (P=0.0098, Cohen's d=0.40) and for the PANSS Negative scale (P=0.028, Cohen's d=0.33). Treatment-emergent adverse events were reported at similar frequencies across all treatment groups (39.0% with placebo, 23.4% with encenicline 0.27 mg, and 33.3% with encenicline 0.9 mg). Overall, encenicline was generally well tolerated and demonstrated clinically meaningful improvements in cognition and function in patients with schizophrenia.


[What investigations should be done following the first episode of pulmonary embolism?].
Thromboembolic venous disease is both common and potentially serious, thus the first episode of pulmonary embolus calls for careful assessment. This involves two stages: a search for a venous localization of the pulmonary embolus and a search for risk factors contributing to thromboembolic venous disease. The emergence of non-invasive echographic-Doppler techniques and echocardiography make possible the localization of any residual venous thrombus. The risk of post thrombotic disease is raised in symptomatic thrombotic venous disease which requires wearing elastic stockings for a least two years. On the other hand this risk has not been assessed in asymptomatic cases of venous thrombosis. A search for risk factors requires a detailed history, a rigorous clinical examination and a routine list of laboratory investigations. Some complex investigations for detecting the early stages of a neoplasm would not appear justified unless there is objective evidence to support his. At the same time thrombophilia studies are not currently performed routinely for a first episode but may be suggested in the following cases: family history of thromboembolic venous disease, age less than 45, including those in whom the episode occurs at the same time as pregnancy, or whilst taking hormone therapy, idiopathic thromboembolism, the association of arterial and venous thrombi and finally venous thromboses occurring in an unusual anatomical site. Prospective studies have shown the value of long term anticoagulation in patients suffering from constitutional hemostatic anomalies. Finally, if there is an after thought of occult cancer or constitutional thrombocytopenia a careful follow up should be performed particularly during the first year.


Prosthetic vascular graft infection through a median sternotomy: a multicentre review †.
The aim of this study is to analyse the treatment outcomes of thoracic prosthetic graft infection. A retrospective chart review was conducted at six hospitals and included the records of 68 patients treated for postoperative prosthetic vascular graft infection (mean age: 62.3 ± 15.1, male 51) from January 2000 to December 2013. The number of patients and the locations of the treated infections were as follows: 13 for aortic root, 16 for ascending aorta, 35 for aortic arch and 4 for aortic root to arch. In-hospital infection occurred in 43 patients and after discharge in 25. The mean follow-up time was 2.0 ± 2.3 years. The follow-up rate was 94.1%. The most commonly isolated micro-organism was Staphylococcus aureus (72.1%). Rereplacement of infectious graft was performed in 18 patients (Dacron graft in 12, homograft in 4 and rifampicin-bonded Dacron graft in 2). The overall hospital mortality rate was 35.3% (24/68). The mortality rate among the patients with graft rereplacement was 33.3% (6/18), with pedicled muscle flaps or pedicled omental flaps to cover the graft 25.9% (7/27), with irrigation 55.0% (11/20) and on antibiotic therapy only 0% (0/3). Our multivariate analysis demonstrated that the risk factors of hospital death increased in the absence of pedicled flaps (muscle or omentum) to cover the graft (P = 0.001), age over 55 (P = 0.003), time from onset of initial operation <1 week (P = 0.031) and period before 2008 (P = 0.001). The overall 1-year survival rate was 58.6%. The treatment outcomes of thoracic prosthetic vascular graft infection have not been satisfactory. However, the use of pedicled muscle or omental flaps to cover the graft could improve the outcomes.


State-Level Disparity in Lung Cancer Survival in the United States.
Rationale: The cancer mortality-to-incidence ratio (MIR) can serve as a population-based indicator for cancer care outcomes. In the US, evaluation of lung cancer survival by individual states has not been evaluated. Objective: To assess the association between lung cancer survival by using MIRs and state-level health disparities in the United States. Methods: We calculated 5-year lung cancer MIR averages from 2011 to 2015 using the United States Cancer Statistics (USCS) data. America's Health Rankings (AHR) is a platform using weighted measures in five different categories to calculate annual state health rankings. Five-year averages from 2011 to 2015 of the health uninsured rate and 4-year averages from 2011 to 2014 of health spending per capita were obtained from the U.S. Census Bureau and Centers for Medicare & Medicaid Services. Linear regression analyses were performed to determine the associations between cancer survival value (CSV) = (1 - MIR) × 100% and state health variables. Results: During the study period, the 5-year averages of age-adjusted incidence, mortality rates, and CSVs were 60.3 ± 2.1 per 100,000 population, 43.4 ± 2.1 per 100,000, and 27.9 ± 3.9%, respectively. Among the 50 states, Connecticut had the highest CSV (38.6 ± 1.7%) whereas Nevada had the lowest CSV (18.7 ± 6.5%). Hawaii had the highest health ranking and Mississippi had the lowest ranking in 2016. States with better health rankings, lower health uninsured rates, and higher health spending were significantly associated with higher CSVs (R 2 = 0.418, P < 0.001; R 2 = 0.352, P < 0.001; R 2 = 0.142, P = 0.007, respectively). Conclusions: There are significant differences in lung cancer survival within the United States. Lung cancer survival by using CSV was strongly associated with state health disparities, and it can be an applicable measure to evaluate the state-level health disparities in the United States.


Midazolam and awareness with recall during total intravenous anaesthesia.
A double-blind study was undertaken to evaluate the influence of graded doses of midazolam on propofol infusion requirements, recovery characteristics and the quality of recovery, associated with propofol/alfentanil/O2 total intravenous anaesthesia (TIVA). Ninety ASA Class I and II subjects scheduled for arthroscopic knee surgery were randomly allocated to receive either placebo (Group PLAC), or midazolam doses of 15, 30 or 45 micrograms.kg-1 (Groups M-15, M-30 and M-45, respectively). Anaesthesia was induced and maintained with propofol (infused initially at 100 micrograms.kg-1.min-1, and adjusted there after according to anaesthetic depth) and alfentanil (loading dose of 20 micrograms.kg-1, followed by infusion at 0.5 microgram.kg-1. min-1). Postoperatively, times to awakening, recovery, and discharge were evaluated, in addition to psychometric evaluations using the Trieger Dot Test (TDT). The study was discontinued prematurely, as six patients unexpectedly experienced intraoperative awareness with recall (4/21 = 19.1% of patients with PLAC vs 2/69 = 2.9% of patients in the midazolam groups, P < 0.04). Induction requirements of propofol were found to be lower in the M-30 and M-45 groups when compared with PLAC (P < 0.05), whereas propofol infusion requirements were similar among groups. Times to awakening and discharge from the Recovery Room and Day Care Unit, as well as TDT scores, were no greater in any midazolam group than in PLAC. Midazolam 30-45 micrograms.kg-1 decreases the amount of propofol required for anaesthetic induction, without influencing recovery profiles or patient discharge times from the Day Care Unit. Despite careful modulation of the propofol infusion rate, six patients unexpectedly experienced intraoperative awareness with recall, with the lowest incidence occurring in those groups where patients had received midazolam.


Serum myostatin is reduced in individuals with metabolic syndrome.
Myostatin is a negative regulator of skeletal muscle mass and may also modulate energy metabolism secondarily. We aim to investigate the relationship between serum myostatin and the metabolic variables in diabetic (DM) and non-diabetic subjects. A cross-sectional study recruiting 246 consecutive DM patients and 82 age- and gender-matched non-diabetic individuals at a medical center was conducted. The variables of anthropometry and blood chemistry were obtained. Serum myostatin level was measured with enzyme immunoassay. DM group had lower serum myostatin compared with non-diabetics (7.82 versus 9.28 ng/ml, p<0.01). Sixty-two percent of the recruited individuals had metabolic syndrome (MetS). The patients with MetS had significantly lower serum myostatin than those without (7.39 versus 9.49 ng/ml, p<0.001). The serum myostatin level decreased with increasing numbers of the MetS components (p for trend<0.001). The patients with higher body mass index, larger abdominal girth, lower high-density lipoprotein cholesterol (HDL-C), and higher triglycerides had lower serum myostatin than those without. The serum myostatin level was independently negatively related to larger abdominal girth, higher triglycerides, and lower HDL-C after adjustment. The odds ratios for MetS, central obesity, low HDL-C, high triglycerides, and DM were 0.85, 0.88, 0.89, 0.85, and 0.92, respectively, when serum myostatin increased per 1 ng/mL, in the binary logistic regression models. Lower serum myostatin independently associated with MetS, central obesity, low HDL-C, and high triglycerides after adjustment. Higher serum myostatin is associated with favorable metabolic profiles.


Anti-inflammatory, gastroprotective and anti-ulcerogenic effects of red algae Gracilaria changii (Gracilariales, Rhodophyta) extract.
Gracilaria changii (Xia et Abbott) Abbott, Zhang et Xia, a red algae commonly found in the coastal areas of Malaysia is traditionally used for foods and for the treatment of various ailments including inflammation and gastric ailments. The aim of the study was to investigate anti-inflammatory, gastroprotective and anti-ulcerogenic activities of a mass spectrometry standardized methanolic extract of Gracilaria changii. Methanolic extract of Gracilaria changii (MeOHGCM6 extract) was prepared and standardized using mass spectrometry (MS). Anti-inflammatory activities of MeOHGCM6 extract were examined by treating U937 cells during its differentiation with 10 μg/ml MeOHGCM6 extract. Tumour necrosis factors-α (TNF-α) response level and TNF-α and interleukin-6 (IL-6) gene expression were monitored and compared to that treated by 10 nM betamethasone, an anti-inflammatory drug. Gastroprotective and anti-ulcerogenic activities of MeOHGCM6 extract were examined by feeding rats with MeOHGCM6 extract ranging from 2.5 to 500 mg/kg body weight (b.w.) following induction of gastric lesions. Production of mucus and gastric juice, pH of the gastric juice and non-protein sulfhydryls (NP-SH) levels were determined and compared to that fed by 20 mg/kg b.w. omeprazole (OMP), a known anti-ulcer drug. MS/MS analysis of the MeOHGCM6 extracts revealed the presence of methyl 10-hydroxyphaeophorbide a and 10-hydroxypheophytin a, known chlorophyll proteins and several unidentified molecules. Treatment with 10 μg/ml MeOHGCM6 extract during differentiation of U937 cells significantly inhibited TNF-α response level and TNF-α and IL-6 gene expression. The inhibitory effect was comparable to that of betamethasone. No cytotoxic effects were recorded for cells treated with the 10 μg/ml MeOHGCM6 extract. Rats fed with MeOHGCM6 extract at 500 mg/kg b.w. showed reduced absolute ethanol-induced gastric lesion sizes by > 99% (p < 0.05). This protective effect was comparable to that conferred by OMP. The pH of the gastric mucus decreased in dose-dependent manner from 5.51 to 3.82 and there was a significant increase in NP-SH concentrations. Results from the study, suggest that the mass spectrometry standardized methanolic extract of Gracillaria changii possesses anti-inflammatory, gastroprotective and anti-ulcerogenic properties. Further examination of the active constituent of the extract and its mechanism of action is warranted in the future.


Culture and complex interventions: lessons for evidence, policy and practice.
Evidence-based mental healthcare is evolving rapidly. There is a need for well-tested and effective interventions that are suited to culturally diverse populations. This editorial considers the findings from the SITARA study. There are a substantial number of implications for research, policy and practice.


Active cytotoxic necrotizing factor 1 associated with outer membrane vesicles from uropathogenic Escherichia coli.
Cytotoxic necrotizing factor type 1 (CNF1) is one of the virulence factors produced by uropathogenic Escherichia coli (UPEC). How this toxin is translocated from the bacterial cytoplasm to the surrounding environment is not well understood. Our data suggest that CNF1 may be regarded as a secreted protein, since it could be detected in culture supernatants. Furthermore, we found that CNF1 was tightly associated to outer membrane vesicles, suggesting that such vesicles play a role in the secretion of this protein. Interestingly, vesicle samples containing CNF1 could exert the effects known for this protein on HeLa cell cultures, showing that CNF1 is transported by vesicles in its active form. Taken together, our results strongly suggest that outer membrane vesicles could be a means for the bacteria to deliver CNF1 to the environment and to the infected tissue. In addition, our results indicate that the histone-like nucleoid structuring protein H-NS has a role in the downregulation of CNF1 production and that it affects the outer membrane vesicle release in UPEC strain J96.


Proposing an International Standard Accident Number for Interconnecting Information and Communication Technology Systems of the Rescue Chain.
The rapid dissemination of smart devices within the internet of things (IoT) is developing toward automatic emergency alerts which are transmitted from machine to machine without human interaction. However, apart from individual projects concentrating on single types of accidents, there is no general methodology of connecting the standalone information and communication technology (ICT) systems involved in an accident: systems for alerting (e.g., smart home/car/wearable), systems in the responding stage (e.g., ambulance), and in the curing stage (e.g., hospital). We define the International Standard Accident Number (ISAN) as a unique token for interconnecting these ICT systems and to provide embedded data describing the circumstances of an accident (time, position, and identifier of the alerting system). Based on the characteristics of processes and ICT systems in emergency care, we derive technological, syntactic, and semantic requirements for the ISAN, and we analyze existing standards to be incorporated in the ISAN specification. We choose a set of formats for describing the embedded data and give rules for their combination to generate an ISAN. It is a compact alphanumeric representation that is generated easily by the alerting system. We demonstrate generation, conversion, analysis, and visualization via representational state transfer (REST) services. Although ISAN targets machine-to-machine communication, we give examples of graphical user interfaces. Created either locally by the alerting IoT system or remotely using our RESTful service, the ISAN is a simple and flexible token that enables technological, syntactic, and semantic interoperability between all ICT systems in emergency care.


Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1.
The essential fatty acid eicosapentaenoic acid (EPA) present in fish oils displays beneficial effects in a range of human disorders associated with inflammation including cardiovascular disease. Resolvin E1 (RvE1), a new bioactive oxygenated product of EPA, was identified in human plasma and prepared by total organic synthesis. Results of bioaction and physical matching studies indicate that the complete structure of RvE1 is 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA. At nanomolar levels, RvE1 dramatically reduced dermal inflammation, peritonitis, dendritic cell (DC) migration, and interleukin (IL) 12 production. We screened receptors and identified one, denoted earlier as ChemR23, that mediates RvE1 signal to attenuate nuclear factor-kappaB. Specific binding of RvE1 to this receptor was confirmed using synthetic [(3)H]-labeled RvE1. Treatment of DCs with small interference RNA specific for ChemR23 sharply reduced RvE1 regulation of IL-12. These results demonstrate novel counterregulatory responses in inflammation initiated via RvE1 receptor activation that provide the first evidence for EPA-derived potent endogenous agonists of antiinflammation.


Codon Optimization Significantly Improves the Expression Level of α -Amylase Gene from Bacillus licheniformis in Pichia pastoris.
α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinant α-amylase from Bacillus licheniformis (B. licheniformis), the α-amylase gene from B. licheniformis was optimized according to the codon usage of Pichia pastoris (P. pastoris) and expressed in P. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level in P. pastoris after methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate for α-amylase production in industrial use.


Assessing Genetic Algorithm-Based Docking Protocols for Prediction of Heparin Oligosaccharide Binding Geometries onto Proteins.
Although molecular docking has evolved dramatically over the years, its application to glycosaminoglycans (GAGs) has remained challenging because of their intrinsic flexibility, highly anionic character and rather ill-defined site of binding on proteins. GAGs have been treated as either fully "rigid" or fully "flexible" in molecular docking. We reasoned that an intermediate semi-rigid docking (SRD) protocol may be better for the recapitulation of native heparin/heparan sulfate (Hp/HS) topologies. Herein, we study 18 Hp/HS-protein co-complexes containing chains from disaccharide to decasaccharide using genetic algorithm-based docking with rigid, semi-rigid, and flexible docking protocols. Our work reveals that rigid and semi-rigid protocols recapitulate native poses for longer chains (5→10 mers) significantly better than the flexible protocol, while 2→4-mer poses are better predicted using the semi-rigid approach. More importantly, the semi-rigid docking protocol is likely to perform better when no crystal structure information is available. We also present a new parameter for parsing selective versus non-selective GAG-protein systems, which relies on two computational parameters including consistency of binding (i.e., RMSD) and docking score (i.e., GOLD Score). The new semi-rigid protocol in combination with the new computational parameter is expected to be particularly useful in high-throughput screening of GAG sequences for identifying promising druggable targets as well as drug-like Hp/HS sequences.


Human intraocular filariasis caused by Dirofilaria sp. nematode, Brazil.
A case of human intraocular dirofilariasis is reported from northern Brazil. The nematode was morphologically and phylogenetically related to Dirofilaria immitis but distinct from reference sequences, including those of D. immitis infesting dogs in the same area. A zoonotic Dirofilaria species infesting wild mammals in Brazil and its implications are discussed.


Wedge resection and radiofrequency ablation for stage I nonsmall cell lung cancer.
The main aim of this study was to compare radiofrequency ablation (RFA) and wedge resection in terms of disease recurrence and survival, as intent-to-treat therapy for stage I nonsmall cell lung cancer (NSCLC) in marginal or non-surgical candidates. 121 high-risk patients, treated for stage I NSCLC with wedge resection (n=59) or RFA (n=62) in a 7-year period, were analysed. Age, sex, comorbidity score, performance status, forced expiratory volume in 1 s and forced vital capacity values, body mass index, T-stage and histology were evaluated as possible risk factors affecting disease recurrence and survival. At a median follow-up of 36 and 42 months for wedge resection and for RFA (p=0.232), local recurrence rate was 2 and 23%, respectively (p=0.002). The 1-, 2- and 5-year overall survival (disease-free interval) rates were 100% (96%), 96% (90%) and 52% (76%) for wedge resection, and 93% (87%), 72% (63%), and 35% (55%) for RFA (p=0.044 and p=0.01, respectively). None of the analysed parameters was found to be risk factor for disease recurrence and survival, except stage T2, which significantly affected disease-recurrence, overall and cancer-related survival and disease-free interval in the RFA group. Whenever possible, surgical resection, even if limited, should be preferred due to its higher disease control and survival rates. RFA can be considered a valid option for inoperable patients, especially for those with stage T1N0.


Lived Experiences of an Elite Performance Management Team Through Injury Rehabilitation: An Interpretative Phenomenological Analysis.
Injury is a common and challenging experience for many athletes, and return-to-sport outcomes have been persistently poor despite advancements in research and practice. To ameliorate this challenge and to bridge a gap that exists in the sport injury literature between theoretical conceptualization and intervention design, research is needed to explore team-based approaches to professional practice. The current study aimed to begin this work through exploration of a single performance management team (PMT) through 2 injury and rehabilitation cases leading into and across the 2014 Olympic Winter Games. Qualitative, interpretative phenomenological analysis. Interviews were conducted with the 5 members of the PMT (coach, physiotherapist, sport psychology consultant, case manager, and athlete) involved in both injury cases. Lower-order and higher order themes were identified and interpreted through the extent literature. Results indicate that 3 higher order themes interacted to impact the lived experiences of the PMT members across the 2 injury cases. Participants described the sociocultural context that surrounded the team, the individual struggles they faced, and the functioning of the team as the primary contributors to their lived experiences as well as observed rehabilitation outcomes. Findings of this study mirror previous research in team science within the general health care domain, and prompt ongoing exploration of how to improve the experiences for PMT members as well as rehabilitation and return-to-sport outcomes for athletes.


Preoperative anxiety in children. Predictors and outcomes.
To determine predictors and behavioral outcomes of preoperative anxiety in children undergoing surgery. A prospective, longitudinal study. A university children's hospital. One hundred sixty-three children, 2 to 10 years of age (and their parents), who underwent general anesthesia and elective surgery. In the preoperative holding area, anxiety level of the child and parents was determined using self-reported and independent observational measures. At separation to the operating room, the anxiety level of the child and parents was rated again. Postoperative behavioral responses were evaluated 3 times (at 2 weeks, 6 months, and 1 year). A multiple regression model (R2 = 0.58, F = 6.4, P = .007) revealed that older children and children of anxious parents, who received low Emotionality, Activity, Sociability, and Impulsivity (EASI) ratings for activity, and with a history of poor-quality medical encounters demonstrated higher levels of anxiety in the preoperative holding area. A similar model (R2 = 0.42, F = 8.6, P = .001) revealed that children who received low EASI ratings for activity, with a previous hospitalization, who were not enrolled in day care, and who did not undergo premedication were more anxious at separation to the operating room. Overall, 54% of children exhibited some negative behavioral responses at the 2-week follow-up. Twenty percent of the children continued to demonstrate negative behavior changes at 6-month follow-up, and, in 7.3% of the children, these behaviors persisted at 1-year follow-up. Nightmares, separation anxiety, eating problems, and increased fear of physicians were the most common problems at 2-week follow-up. Multivariate analysis demonstrated that child's age, number of siblings, and immediate preoperative anxiety of the child and mother predicted later behavioral problems. Variables such as situational anxiety of the mother, temperament of the child, age of the child, and quality of previous medical encounters predict a child's preoperative anxiety. Although immediate negative behavioral responses develop in a relatively large number of young children following surgery, the magnitude of these changes is limited, and long-term maladaptive behavioral responses develop in only a small minority.


[Factors affecting mobilization of peripheral blood stem/progenitor cells and apheresis efficiency from healthy donors by rhG-CSF].
This study was aimed to explore the factors impacting on effect of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) in mobilizing and collecting peripheral blood stem/progenitor cells (PBSPC) from healthy donors, and to determine the optimal time for PBSPC harvest. A mobilization course in 431 healthy donors was retrospectively studied and the factors influencing the efficacy of mobilization were analyzed. The normal donors underwent leukapheresis for PBSPC collection in multicentres after mobilization with G-CSF administered. A variety of items analyzed included donor age, sex, weight, body mass index (BMI), daily G-CSF dose and schedule of G-CSF administration. The results showed that G-CSF was administered subcutaneously at median 5.7 microg/kg for mobilization for 3 - 5 days, The median number of peripheral blood mononuclear cells (PBMNC) count of per kg recipient weight was 9.57 x 10(8) and CD34(+) cells per kg recipient weight was 4.91 x 10(6) after a median of 1.7 leukapheresis. The side effects were mild and well tolerated. By univariate analysis, BMI, daily G-CSF dose and schedule of administration were significantly correlated with the yield of PBMNCs, CD34(+) cells. The best apheresis yields of PBMNCs and CD34(+) cells were achieved on day 5 after treatment with rhG-CSF. Because the narrow range and low dose of rhG-CSF administration, there were minor effects of rhG-CSF dose compared with schedule of administration. It is concluded that mobilization and leukapheresis are safe in healthy donors and that the low dose of rhG-CSF in 5-day administration are probably optimal for donor management.


Ruthenium(II)-Polypyridyl Compounds with π-Extended Nitrogen Donor Ligands Induce Apoptosis in Human Lung Adenocarcinoma (A549) Cells by Triggering Caspase-3/7 Pathway.
Ru(II)-polypyridyl complexes exhibit antitumor properties that can be systematically tailored by means of adjusting the ligand environment. In this work, the effect of incorporating π-extended moieties into anionic N∧O- based chelating ligands on the cytotoxic properties of Ru compounds is explored. Four new Ru(II) complexes, [Ru(bpy)2(dphol)][PF6] (1; bpy = 2,2'-bipyridine, dphol = dibenzo[ a, c]phenazin-10-olate), [Ru(phen)2(dphol)][PF6] (2; phen = 1,10-phenanthroline), [Ru(bpy)2(hbtz)][PF6] (3; hbtz = 2-(benzo[ d]thiazol-2-yl)phenolate), and [Ru(phen)2(hbtz)][PF6] (4) were synthesized and thoroughly characterized. In vitro cytotoxicity was investigated in human lung adenocarcinoma (A549) cells, which revealed that 4 is the most cytotoxic compound (IC50 = 0.8 μM) in the series including a control compound [Ru(bpy)2(quo)][PF6] (5; quo = 8-hydroxyquinolinate) and is nearly 8-fold more cytotoxic than cisplatin. An investigation of the mechanism of cell death led to the finding that compounds 1-4 disrupt the mitochondrial transmembrane potential (ΔΨm) in a concentration-dependent fashion, which is an event associated with the intrinsic pathway of apoptosis. Moreover, compound 4 triggers the activity of caspase-3/7, which eventually induces the apoptotic cellular death of A549 cells. Thus, increasing the overall lipophilicity of the Ru compounds by introducing π-extended moieties in the anionic N∧O- ligand is a successful strategy for realizing a new family of pro-apoptotic compounds with a [RuIIN5O]+ coordination environment.


Determination of the mutations responsible for the Lesch-Nyhan syndrome in 17 subjects.
Hypoxanthine--guanine phosphoribosyltransferase (HPRT) is a purine salvage enzyme that catalyzes the conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. Previous studies of mutant HPRT proteins analyzed at the molecular level have shown a significant heterogeneity. This investigation further verifies this heterogeneity and identifies insertions, deletions, and point mutations. The direct sequencing of the polymerase chain reaction-amplified product of reverse-transcribed HPRT mRNA enabled the rapid identification of the mutations found in 17 previously uncharacterized cell lines derived from patients with the Lesch-Nyhan syndrome.


Lipoprotein (a): an emerging risk factor for atherosclerosis.
Lipoprotein (a) is an antigenic variant of low density lipoprotein and is present in the plasma of most people. Many epidemiologic studies from Europe and North America have found that when plasma levels of lipoprotein (a) exceed 0.20 g/L, there is a significantly higher risk of coronary and cerebrovascular atherosclerosis. Until recently, there has been little insight into the function of lipoprotein (a) or its potential atherogenic mechanism. Molecular biological studies have shown that the characteristic protein of lipoprotein (a), called apolipoprotein (a), strongly resembles plasminogen, the precursor of the natural anticoagulant plasmin. Furthermore, there is emerging evidence that lipoprotein (a) is the missing link between the lipoprotein and coagulation systems, acting perhaps as a vehicle which delivers cholesterol to the site of intravascular damage, or as an inhibitor of plasminogen activation at the site of an evolving thrombus.


[Research Progress and Prospect Analysis of Vascular Interventional Surgical Robot].
Vascular interventional surgery is an important means to treat cardiovascular and cerebrovascular diseases, but the particularity of its working environment will bring greater radiation threat to doctors. Vascular interventional surgery robots can effectively improve the working environment of doctors and can provide more stable operations, improve the success rate of surgery. This study mainly introduces the current research status, key technologies, and future application of vascular interventional surgical robots.


Magnetoencephalography source localization using the source affine image reconstruction (SAFFIRE) algorithm.
Nonparametric iterative algorithms have been previously proposed to achieve high-resolution, sparse solutions to the bioelectromagnetic inverse problem applicable to multichannel magnetoencephalography and EEG recordings. Using a mmse estimation framework, we propose a new algorithm of this type denoted as source affine image reconstruction (SAFFIRE) aiming to reduce the vulnerability to initialization bias, augment robustness to noise, and decrease sensitivity to the choice of regularization. The proposed approach operates in a normalized lead-field space and employs an initial estimate based on matched filtering to combat the potential biasing effect of previously proposed initialization methods. SAFFIRE minimizes difficulties associated with the selection of the most appropriate regularization parameter by using two separate loading terms: a fixed noise-dependent term that can be directly estimated from the data and arises naturally from the mmse formulation, and an adaptive term (adjusted according to the update of the source estimate) that accounts for uncertainties of the forward model in real-experimental applications. We also show that a noncoherent integration scheme can be used within the SAFFIRE algorithm structure to further enhance the reconstruction accuracy and improve robustness to noise.


Critical Advances in Ambient Air Operation of Nonaqueous Rechargeable Li-Air Batteries.
Over the past few years, great attention has been given to nonaqueous lithium-air batteries owing to their ultrahigh theoretical energy density when compared with other energy storage systems. Most of the research interest, however, is dedicated to batteries operating in pure or dry oxygen atmospheres, while Li-air batteries that operate in ambient air still face big challenges. The biggest challenges are H2 O and CO2 that exist in ambient air, which can not only form byproducts with discharge products (Li2 O2 ), but also react with the electrolyte and the Li anode. To this end, recent progress in understanding the chemical and electrochemical reactions of Li-air batteries in ambient air is critical for the development and application of true Li-air batteries. Oxygen-selective membranes, multifunctional catalysts, and electrolyte alternatives for ambient air operational Li-air batteries are presented and discussed comprehensively. In addition, separator modification and Li anode protection are covered. Furthermore, the challenges and directions for the future development of Li-air batteries are presented.


Measuring resilience with the RS-14: a tale of two samples.
The purpose of this study was to systematically examine the psychometric properties of the 14-item Resilience Scale (RS-14; Wagnild, 2009a). Exploratory and confirmatory factor-analytic methods were employed, including an analysis of measurement invariance models by sex and race/ethnicity. Descriptive statistics, reliability, and validity data were also calculated. Analyses were based on 2 samples, one made up of individuals seeking mental health services following the 2010 Gulf oil spill (N = 1,032) and the other made up of university students (N = 1,765). For both samples, all items loaded (>.30) onto 1 factor, indicating cohesive structure for a 1-factor model explaining 53.2% of the variance in the clinical sample and 67.6% of the variance in the undergraduate sample. Further, the examination of measurement invariance indicated that the RS-14 was similarly structured for sex and race/ethnicity. Reliability coefficients exceeded.90 for both samples and also when data were examined by comparison groups. The RS-14 correlated significantly and as expected with measures of positive concepts (such as perceived meaning in life and satisfaction with life) and indexes of psychological distress (such as depression, anxiety, stress, and posttraumatic stress). These data support the utility of the RS-14 with clinical and undergraduate student samples. Implications for these data are discussed.


The changing face of the exocrine pancreas in cystic fibrosis: pancreatic sufficiency, pancreatitis and genotype.
(Table is included in full-text article.)Cystic fibrosis (CF) is the most frequent cause of exocrine pancreatic insufficiency in childhood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes CFTR protein that functions as cyclic AMP-dependent chloride channel allowing the passage of anions and secondarily water into the lumen of pancreatic ducts. Luminal chlorides are exchanged for bicarbonates. The lack of CFTR channel or its disrupted function (being the consequence of CFTR gene mutations) results in reduced volume of more acidic secretion. It has been suggested that such a situation leads to the precipitation of highly concentrated protein-containing secretion with obstruction and organ damage. The intensity of this process determines the progression of the disease. Steatorrhea is the significant symptom of classical form of CF. Residual pancreatic secretion in a subset of patients, however, allows for normal lipid digestion and absorption. Previous cross-sectional clinical studies estimated that about 85-90% of CF patients in preschool, school and older age are pancreatic insufficient. More frequent detection of mild and nonclassic forms of CF leads to higher frequency of pancreatic sufficiency (PS). The potential decline of exocrine pancreatic function, however, should be always considered. All PS patients with at least one severe or unknown CFTR mutation should be longitudinally assessed for the progression of pancreatic dysfunction. Recurrent acute and chronic pancreatitis is not a rare clinical condition in PS patients with PS: it might be the presenting symptom, even preceding CF diagnosis by several years. Potential appearance of this complication in individuals with pancreatic insufficiency demands elucidation.


Analysis of chromatin structure in vivo.
A number of important nuclear processes including replication, recombination, repair, and transcription involve the interaction of soluble nuclear proteins with DNA assembled as chromatin. Recent progress in a number of experimental systems has focused attention on the influence chromatin structure may exert on gene regulation in eukaryotes. With the advent of new technologies for the analysis of chromatin structure in vivo, studies evaluating the influence of chromatin structure on gene transcription have become feasible for a number of systems. This article serves as an introduction to the use of restriction endonucleases to define nucleosomal organization and characterize changes in this organization that accompany transcriptional activation in vivo. The procedure includes the isolation of intact transcriptionally competent nuclei, limited digestion with specific restriction endonucleases, and purification of the DNA. This DNA serves as the substrate for a linear amplification using single primers that generate enzyme-specific DNA fragments, which are then resolved by electrophoresis. Specific examples related to our studies of the influence of chromatin structure on steroid hormone regulation of transcription from the mouse mammary tumor virus promoter are provided to illustrate this technique and several novel variations. Alternative methods for analysis of chromatin architecture using DNase I, micrococcal nuclease, permanganate, and methidiumpropyl-EDTA-iron(II) are also described. Through the use of these methodologies one is able to determine both the translational and the rotational positions for a given nucleosome as well as quantify changes at a specific nucleosome in response to regulatory and developmental signals.


Breast conserving treatment for breast cancer: dosimetric comparison of sequential versus simultaneous integrated photon boost.
Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB) compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001). There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04). The dose to the organs at risk (OAR) was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine.


Internal training load monitoring in professional football: a systematic review of methods using rating of perceived exertion.
The rate of perceived exertion (RPE) is widely adopted to quantify internal training load (ITL) in professional football. The aim of this study was to systematically review the use RPE-based methods in professional football. Observational studies conducted during training routines of professional football players over a minimum of one-week were selected based on the preferred reporting items for systematic reviews and meta-analyses statement. Thirty-eight articles met the inclusion criteria (average qualitative score was 6.3 out of 10 [3 to 9]). The main deficiencies identified concerned the poor description of study design (~52% of the studies), and the non-quantification of match load (~44%). Ten studies complemented RPE-based ITL information with time-motion analysis (~26%) and seven studies added HR recordings (~18%). Nine studies collected RPE data after complementary training, separately to field sessions (~3%). Operational questions (e.g. How was your workout? ~71%) were preferred to instructions (e.g. Please rate the intensity of today's session; ~8%). Session-RPE (s-RPE; RPE multiplied by training duration) was more commonly adopted as measure of exercise intensity than isolated RPE (~76 vs. ~8%). RPE-derived variables calculated on weekly values included absolute week-to-week change, acute: chronic workload ratio, monotony and strain and were not frequently used (7 to 15%). Four studies (~11%) divided RPE in two components: respiratory and muscular. There is a lack of consensus for the use of RPE in professional football and "good practices" are warranted. This review might help practitioners regarding procedures to adopt in RPE data collection and interpretation.


Methotrexate: a drug of the future in ulcerative colitis?
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is thought to affect 1780000 patients in USA and Europe. Its incidence is increasing rapidly in Asia. Drugs with proven clinical activity that are currently used in UC patients include salicylates, steroids, azathioprine and infliximab. None of them is active in every patient and all carry significant side effects. There is a need for other active drugs in UC. Low dose methotrexate has been used for decades in psoriasis, rheumatoid arthritis and Crohn's disease. In these diseases, it is an active, well tolerated and cheap drug. In UC there have been several open series, most of which are retrospective. Overall, these studies have shown promising results, with response rates of 50 to 72 %. There have been two randomized clinical trials of methotrexate vs placebo in UC. Both were negative but methotrexate was prescribed orally at suboptimal doses. So far, there is no evidence for the efficacy of methotrexate in UC. Therefore, there is a need for clinical trials with methotrexate using adequate dosage and the parenteral route. Two multicenter randomized trials of methotrexate 25 mg/week parenterally vs placebo are either ongoing (METEOR, the European trial) or being built up (MERIT, the US trial). These trials should determine if methotrexate is a valuable therapeutic option in UC.


[Epidermoid cyst of the testicle: presentation of a case].
To describe a case of epidermoid cyst of the testis, a rare lesion that warrants surgical exploration to confirm the diagnosis since its echo patterns are characteristic but not pathognomonic. 10 years earlier the patient had noticed an asymptomatic swelling of the right testis which did not cause infertility since he had two children over the last 6 years. Tumor markers AFP, BHCG and LDH fell within the normal ranges. Ultrasound evaluation with a high resolution 7.5 Mhz transducer revealed a 4 x 3.5 x 3.2 cm testicular mass surrounded by atrophic parenchyma. The patient underwent radical inguinal orchidectomy. Epidermoid cyst is the benign variety of testicular teratoma. Two different forms exist: simple and mixed. Malignant components are present in the latter form. If the simple form is identified before substitution of the testicular parenchyma occurs, testis sparing surgery is justified; otherwise radical orchidectomy with inguinal exploration is indicated.


Coordinate signaling by Src and p38 kinases in the induction of cortical cataracts.
The goals of this study were to determine whether MAP kinase signaling pathways play a role in the formation of lens cataracts and to examine the potential signaling relationship between Src and MAP kinases in signaling the induction of lens opacities. Embryonic day (E)10 chick lenses were cultured in Medium 199 containing 10% fetal bovine serum. The activation state of Src kinases and the MAP kinases extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the lens epithelium was determined over a time course from 10 minutes to 10 days in culture by immunoblot analysis. Src kinase activation was suppressed by exposure to the Src family kinase-specific inhibitor PP1. To examine the role of specific MAP kinases in the development of lens opacities, lenses were grown for 10 days in the presence or absence of inhibitors of ERK (U0126), JNK (SP600125), and p38 (SB203580). Lenses were observed and photographed daily, and the degree of opacification was quantified by using image-analysis software. Within a short time after placing embryonic lenses in culture conditions that induce the formation of cataracts, there occurred a great increase in the activation state of the MAP kinase ERK. Activation of ERK was both rapid and transient. No activation of the MAP kinase JNK was observed in the cataract cultures beyond that which occurred in normal lens epithelium, even though JNK activation is often linked to the cellular response to stress. In contrast, although p38 activation was barely detected in the normal embryonic lens, this stress-activated protein kinase exhibited a robust activation in cataract cultures that was sustained throughout the culture period. Studies conducted to map the cataract signaling pathways indicate that the p38 MAP kinase functions upstream of the Src kinase. To analyze the potential role of ERK, JNK, and p38 in cataract induction, lenses were cultured in the presence of specific MAP kinase inhibitors. Although the inhibitors of ERK and JNK did not interfere with the formation of cataract, p38 inhibitors blocked the development of lens opacities with an efficacy similar to that of the Src kinase inhibitor PP1. Activation of both Src and p38 kinases lead to the induction of cataract.


Cornea-responsive medullary dorsal horn neurons: modulation by local opioids and projections to thalamus and brain stem.
Previously, it was determined that microinjection of morphine into the caudal portion of subnucleus caudalis mimicked the facilitatory effects of intravenous morphine on cornea-responsive neurons recorded at the subnucleus interpolaris/caudalis (Vi/Vc) transition region. The aim of the present study was to determine the opioid receptor subtype(s) that mediate modulation of corneal units and to determine whether opioid drugs affected unique classes of units. Pulses of CO(2) gas applied to the cornea were used to excite neurons at the Vi/Vc ("rostral" neurons) and the caudalis/upper cervical spinal cord transition region (Vc/C1, "caudal" neurons) in barbiturate-anesthetized male rats. Microinjection of morphine sulfate (2.9-4.8 nmol) or the selective mu receptor agonist D-Ala, N-Me-Phe, Gly-ol-enkephalin (DAMGO; 1.8-15.0 pmol) into the caudal transition region enhanced the response in 7 of 27 (26%) rostral units to CO(2) pulses and depressed that of 10 units (37%). Microinjection of a selective delta ([D-Pen(2,5)] (DPDPE); 24-30 pmol) or kappa receptor agonist (U50488; 1.8-30.0 pmol) into the caudal transition region did not affect the CO(2)-evoked responses of rostral units. Caudal units were inhibited by local DAMGO or DPDPE but were not affected by U50,488H. The effects of DAMGO and DPDPE were reversed by naloxone (0.2 mg/kg iv). Intravenous morphine altered the CO(2)-evoked activity in a direction opposite to that of local DAMGO in 3 of 15 units, in the same direction as local DAMGO but with greater magnitude in 4 units, and in the same direction with equal magnitude as local DAMGO in 8 units. CO(2)-responsive rostral and caudal units projected to either the thalamic posterior nucleus/zona incerta region (PO/ZI) or the superior salivatory/facial nucleus region (SSN/VII). However, rostral units not responsive to CO(2) pulses projected only to SSN/VII and caudal units not responsive to CO(2) projected only to PO/ZI. It was concluded that the circuitry for opioid analgesia in corneal pain involves multiple sites of action: inhibition of neurons at the caudal transition region, by intersubnuclear connections to modulate rostral units, and by supraspinal sites. Local administration of opioid agonists modulated all classes of corneal units. Corneal stimulus modality was predictive of efferent projection status for rostral and caudal units to sensory thalamus and reflex areas of the brain stem.


Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.
Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP.Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term).Assessment of outcomes will be blinded and will follow the intention-to-treat principle. We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. ISRCTN: ISRCTN58719694.


[Reactions of neurons of the reticular and ventral anterior thalamic nuclei to electrical stimulation of the centrum medianum of the thalamus].
Responses of 145 reticular (R) and 158 ventral anterior (VA) thalamic neurons to electrical stimulation of centrum medianum (CM) were studied in cats anaesthetized with thiopental sodium (30-40 mg/kg intraperitoneally) and immobilized with d-tubocurarine (1 mg/kg). 4.1% of R and 4.4% of VA neurons under study responded to CM stimulation by antidromic spike (latency 0.3-2.0 ms). The conduction velocity of antidromic excitation in axons of those neurons was found to be 1.7-7.6 m/s. There were neurons which responded by antidromic spike to the other thalamic nuclei stimulation as well as to CM. This fact is the electrophysiological proof of the axonal branching in these neurons. 53.8% of R and 46.9% of VA neurons responded to CM stimulation with orthodromic excitation. Two groups of cells were separated among neurons excited orthodromically. The first group neurons responded to CM stimulation by discharges composed of 6-12 spikes with frequency of 130-640 per second. The neurons of the second group generated a single spike. Inhibitory reactions were noticed only in 0.7% of R and in 4.4% of VA neurons. It is shown that afferent impulses from relay nuclei, lateral posterior nucleus and motor cortex converged to some R and VA neurons responding to CM.


Ultrasonic plaque echolucency and emboli signals predict stroke in asymptomatic carotid stenosis.
Better methods are required to identify patients with asymptomatic carotid stenosis (ACS) at risk of future stroke. Two potential markers of high risk are echolucent plaque morphology on carotid ultrasound and embolic signals (ES) in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound (TCD). We explored the predictive value of a score based on these 2 measures in the prospective, observational, international multicenter Asymptomatic Carotid Emboli Study. A total of 435 recruited subjects with ACS ≥70% had baseline ultrasound images and TCD data available. Subjects were prospectively followed up for 2 years. A total of 164 (37.7%) plaques were graded as echolucent. Plaque echolucency at baseline was associated with an increased risk of ipsilateral stroke alone (hazard ratio [HR] 6.43, 95% confidence interval [CI] 1.36-30.44, p = 0.019). A combined variable of plaque echolucency and ES positivity at baseline was associated with a markedly increased risk of ipsilateral stroke alone (HR 10.61, 95% CI 2.98-37.82, p = 0.0003). This association remained significant after controlling for risk factors, degree of carotid stenosis, and antiplatelet medication. Plaque morphology assessed using a simple, and clinically applicable, visual rating scale predicts ipsilateral stroke risk in ACS. The combination of ES detection and plaque morphology allows a greater prediction than either measure alone and identifies a high-risk group with an annual stroke risk of 8%, and a low-risk group with a risk of <1% per annum. This risk stratification may prove useful in the selection of patients with ACS for endarterectomy.


An updated pediatric perspective on the Apert syndrome.
This review of the Apert syndrome, based on our research experience with 136 cases, provides a clinically relevant pediatric perspective. The brain is megalencephalic, resulting in a disproportionately high cranium and a mean birth length and weight above the 50th percentile. The growth pattern in childhood consists of a slowing of linear growth so that most values fall between the 5th and 50th percentiles. From adolescence to adulthood, slowing becomes more pronounced. Central nervous system abnormalities may occur in some cases, including malformations of the corpus callosum and limbic structures, gyral abnormalities, hypoplastic white matter, and heterotopic gray matter. Distortion ventriculomegaly is found because of the large brain in a misshapen skull. Progressive hydrocephalus is uncommon. Intelligence in patients with the Apert syndrome varies from normality to mental deficiency. Early release of the coronal suture and advancement and reshaping of the frontal bone reduce further dysmorphic and unwanted growth changes in the skull, but probably do not affect mentation. Associated cardiovascular and genitourinary anomalies occur in 10% and 9.6% of cases, respectively. Other important findings reviewed include upper- and lower-airway compromise, calvarial development, cervical vertebral anomalies, limb defects, ocular and otologic manifestations, and dermatologic characteristics.


Coxsackievirus B-3 myocarditis. Acute and chronic forms of the disease caused by different immunopathogenic mechanisms.
Male BALB/c, DBA/2 and A mice inoculated with a myocarditic variant of coxsackievirus group B, Type 3 (CVB3) developed three distinct patterns of myocarditis. Most BALB/c and all DBA/2 mice developed acute cardiac inflammation lasting only 2 weeks, while A animals consistently showed twice as much myocardial damage as the other two strains, with active myocarditis continuing for 56 days after virus inoculation. Although virus elimination from the heart was also delayed in A mice, immunopathogenic, not viral, mechanisms caused cardiac injury in all strains. In vivo depletion of L3T4+ (T helper) and Lyt 2+ (T cytolytic/suppressor) cells using monoclonal antibodies showed that myocarditis in BALB/c mice depended predominantly on Lyt 2+ cells, in DBA/2 mice on L3T4+ cells and in A mice on both Lyt 2+ and L3T4+ cells. IgM heart reactive antibodies (HRAs) occurred in all three strains, while IgG HRAs were detected only in DBA/2 and A mice. Presumably, only the IgG antibody was pathogenic in this system. These data suggest that the host's genetic makeup determines the type of immune response to CVB3 infection of the heart and therefore the pattern of myocarditis which develops.


Window into the complexities of chromosome interactomes.
DNA is folded into increasingly complex yet highly mobile structures to organize the chromosomes. In the interphase nucleus, chromosomes or part of the chromosomes encounter one another preferentially at the boundaries between chromosomal territories. Although this situation implies that the preferred chromosomal neighborhood is a key determinant of interactions between chromosomes, what this means in functional terms is currently not well understood. Using the H19 imprinting control region as a window, it has been demonstrated that epigenetic information of the primary chromatin fiber has dual functions. Thus, epigenetic marks not only influence the proximity between chromatin fibers but also transfer epigenetic states between chromatin fibers both in cis and in trans. High-throughput sequence and DNA fluorescence it situ hybridization (FISH) analyses reveal that these features require chromatin movements that are restricted in space and time. The mechanisms involved in the establishment of chromosome interactomes may provide insight of fundamental importance into pivotal regulatory processes in the nucleus, such as the coordination of transcriptional programs and replication timing.


Prospective evaluation of two clinical scores for acute asthma in children 18 months to 7 years of age.
The objective was to evaluate the discriminatory ability of two clinical asthma scores, the Preschool Respiratory Assessment Measure (PRAM) and the Pediatric Asthma Severity Score (PASS), during an asthma exacerbation. This was a prospective cohort study in an academic pediatric emergency department (ED; 60,000 visits/year) conducted from March 2006 to October 2007. All patients 18 months to 7 years of age who presented for an asthma exacerbation were eligible. The primary outcome was a length of stay (LOS) of >6 hours in the ED or admission to the hospital. Clinical findings and components of the PRAM and the PASS were assessed by a respiratory therapist (RT) at the start of the ED visit and after 90 minutes of treatment. During the study period, 3,845 patients were seen in the ED for an asthma exacerbation. Of these, 291 were approached to participate, and eight refused. Moderate levels of discrimination were found between a LOS of >6 hours and/or admission and PRAM (area under the receiver-operating characteristic curve [AUC] = 0.69, 95% confidence interval [CI] = 0.59 to 0.79) and PASS (AUC = 0.70, 95% CI = 0.60 to 0.80) as calculated at the start of the ED visit. Significant similar correlations were seen between the physician's judgment of severity and PRAM (r = 0.54, 95% CI = 0.42 to 0.65) and PASS (r = 0.55, 95% CI = 0.43 to 0.65). The PRAM and PASS clinical asthma scores appear to be measures of asthma severity in children with discriminative properties.


[Study on fingerprint spectrum of loquat leaf by HPLC].
To establish the fingerprint spectrum of Loquat Leaf of Fujian authentic medicinal herbs by HPCE. The HPLC fingerprints of Loquat Leaf were obtained from instrument HP1100. The HPLC separation was performed on a Eclipse XDB-C18 (4.6 mm x 150 mm, 5 microm) analytical column diluted with methanol-l% glacial acetic acid (90:10) at the flow rate of 1.0 ml/min. The temperature of column was room temperature. The UV detection wavelength was 215 nm. Detected 12 batches samples of different species Lopuat Leaf Fingerprint by the method of HPLC. Eight peaks in the chromatogram were common. All the similarity were above 0.9, the fingerprints integer feature were coincident essentially. The method is convenient, quick and exact, and its reproducibility is good. It will be a scientific reference for qualitation identification and quality evaluation of Loquat Leaf.