Adherence to the traditional Mediterranean diet and mortality in subjects with diabetes. Prospective results from the MOLI-SANI study.
Adherence to the Mediterranean diet is associated with lower mortality in a general population but limited evidence exists on the effect of a Mediterranean diet on mortality in subjects with diabetes. We aim to examine the association between the Mediterranean diet and mortality in diabetic individuals. Prospective cohort study on 1995 type 2 diabetic subjects recruited within the MOLI-SANI study. Food intake was recorded by the European Project Investigation into Cancer and Nutrition food frequency questionnaire. Adherence to the Mediterranean diet was appraised by the Greek Mediterranean diet score. Hazard ratios were calculated using multivariable Cox-proportional hazard models. During follow-up (median 4.0 years), 109 all-cause including 51 cardiovascular deaths occurred. A 2-unit increase in Mediterranean diet score was associated with 37% (19%-51%) lower overall mortality. Data remained unchanged when restricted to those being on a hypoglycaemic diet or on antidiabetic drug treatment. A similar reduction was observed when cardiovascular mortality only was considered (hazard ratio = 0.66; 0.46-0.95). A Mediterranean diet-like pattern, originated from principal factor analysis, indicated a reduced risk of overall death (hazard ratio = 0.81; 0.62-1.07). The effect of Mediterranean diet score was mainly contributed by moderate alcohol drinking (14.7% in the reduction of the effect), high intake of cereals (12.2%), vegetables (5.8%) and reduced consumption of dairy and meat products (13.4% and 3.4% respectively). The traditional Mediterranean diet was associated with reduced risk of both total and cardiovascular mortality in diabetic subjects, independently of the severity of the disease. Major contributions were offered by moderate alcohol intake, high consumption of cereals, fruits and nuts and reduced intake of dairy and meat products.


Eight-Coordinate, Stable Fe(II) Complex as a Dual 19F and CEST Contrast Agent for Ratiometric pH Imaging.
Accurate mapping of small changes in pH is essential to the diagnosis of diseases such as cancer. The difficulty in mapping pH accurately in vivo resides in the need for the probe to have a ratiometric response so as to be able to independently determine the concentration of the probe in the body independently from its response to pH. The complex FeII-DOTAm-F12 behaves as an MRI contrast agent with dual 19F and CEST modality. The magnitude of its CEST response is dependent both on the concentration of the complex and on the pH, with a significant increase in saturation transfer between pH 6.9 and 7.4, a pH range that is relevant to cancer diagnosis. The signal-to-noise ratio of the 19F signal of the probe, on the other hand, depends only on the concentration of the contrast agent and is independent of pH. As a result, the complex can ratiometrically map pH and accurately distinguish between pH 6.9 and 7.4. Moreover, the iron(II) complex is stable in air at room temperature and adopts a rare 8-coordinate geometry.


Influenza virus RNA recovered from droplets and droplet nuclei emitted by adults in an acute care setting.
Transmission in hospital settings of seasonal influenza viruses and novel agents such as the Middle East respiratory syndrome coronavirus (MERS-CoV) is well-described but poorly understood. The characterization of potentially infectious bio-aerosols in the healthcare setting remains an important yet ill-defined factor in the transmission of respiratory viruses. Empiric data describing the distribution of bio-aerosols enable discernment of potential exposure risk to respiratory viruses. We sought to determine the distribution of influenza virus RNA emitted into the air by participants with laboratory-confirmed influenza, and whether these emissions had the potential to reach healthcare workers' breathing zones. Two-stage cyclone bio-aerosol samplers from the Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health were placed 0.5-1.0 m (near field) and 2.1-2.5 m (far field) from infected patient participants, as well as in the corridor immediately outside their rooms. In addition, healthcare worker participants providing care to infected participants were recruited to wear a polytetrafluoroethylene (PTFE) filter cassette in their breathing zones. Viral RNA was detected from the air emitted by 37.5% of the 16 participants infected with influenza virus and distributed both in near and far fields and in all tested particle sizes (<1 µm, 1-4 µm, and >4 µm). Viral RNA was recovered in droplet nuclei and beyond 1 m from naturally-infected participants in the healthcare setting and from the breathing zone of one healthcare worker. There was no correlation between patient participant nasal viral load and recovery of viral RNA from the air, and we did not identify any significant association between RNA detection from the air and patient demographics or clinical presentation. A more substantial study is required to identify patient determinants of virus emission into the air and delineate implications for evidence-based policy for prevention and control.


Does participation in a pain course based on the International Association for the Study of Pain's curricula guidelines change student knowledge about pain?
The People in Pain course was set up as a joint initiative of the Departments of Occupational Therapy and Physiotherapy within the School of Health and Rehabilitation Sciences at The University of Queensland. It was instigated in response to the publication of Pain Curricula for Occupational Therapy and Physiotherapy by the International Association for the Study of Pain (IASP) in 1994 (1). The first year it was offered, the "People in Pain" course comprised 14 h of lecture content. It was then expanded to encompass 28 h of lectures and seminar involvement. To evaluate the impact of participation in a university pain course that meets the IASP pain curricula guidelines to increase health professional students' knowledge about pain. Students who participated in the People in Pain course over the first three years were invited to complete the Revised Pain Knowledge and Attitudes Questionnaire (R-PKAQ) pre- and postcourse. Data obtained from 22 students in the short course formed a pilot project, and data from 22 students in the longer version of the course were used in the present study. Examination of the correlation matrix indicated substantial correlations between all R-PKAQ subscales except physiological basis of pain and pharmacological management of pain. In both the pilot project during the first year of the course and the expanded course in the following two years, significant improvement was found in the students' knowledge on five of the six subscales of the R-PKAQ: physiological basis of pain, psychological factors of pain perception, assessment and measurement of pain, cognitive-behavioural methods of pain relief, and pharmacological management of pain. Improvements in the developmental aspects of pain perception subscale failed to reach significance. An integrated pain course developed according to the pain curriculum guidelines developed by the IASP resulted in increased student knowledge regardless of the length of the program attended.


Moderating the outputs of support vector machine classifiers.
In this paper, we extend the use of moderated outputs to the support vector machine (SVM) by making use of a relationship between SVM and the evidence framework. The moderated output is more in line with the Bayesian idea that the posterior weight distribution should be taken into account upon prediction, and it also alleviates the usual tendency of assigning overly high confidence to the estimated class memberships of the test patterns. Moreover, the moderated output derived here can be taken as an approximation to the posterior class probability. Hence, meaningful rejection thresholds can be assigned and outputs from several networks can be directly compared. Experimental results on both artificial and real-world data are also discussed.


Affective facilitation and inhibition of cultural influences on reasoning.
Research in South Korea and the United States examined how affective states facilitate or inhibit culturally dominant styles of reasoning. According to the affect-as-information hypothesis, affective cues of mood influence judgements by serving as embodied information about the value of accessible inclinations and cognitions. Extending this line of research to culture, we hypothesised that positive affect should promote (and negative affect should inhibit) culturally normative reasoning. The results of two studies of causal reasoning supported this hypothesis. Positive and negative affect functioned like "go" and "stop" signals, respectively, for culturally typical reasoning styles. Thus, in happy (compared to sad) moods, Koreans engaged in more holistic reasoning, whereas Americans engaged in more analytic reasoning.


Stationary Patterns in a Two-Protein Reaction-Diffusion System.
Patterns formed by reaction-diffusion mechanisms are crucial for the development or sustenance of most organisms in nature. Patterns include dynamic waves, but are more often found as static distributions, such as animal skin patterns. Yet, a simplistic biological model system to reproduce and quantitatively investigate static reaction-diffusion patterns has been missing so far. Here, we demonstrate that the Escherichia coli Min system, known for its oscillatory behavior between the cell poles, is under certain conditions capable of transitioning to quasi-stationary protein distributions on membranes closely resembling Turing patterns. We systematically titrated both proteins, MinD and MinE, and found that removing all purification tags and linkers from the N-terminus of MinE was critical for static patterns to occur. At small bulk heights, dynamic patterns dominate, such as in rod-shaped microcompartments. We see implications of this work for studying pattern formation in general, but also for creating artificial gradients as downstream cues in synthetic biology applications.


Kaposi's sarcoma-associated herpesvirus LANA protein downregulates nuclear glycogen synthase kinase 3 activity and consequently blocks differentiation.
The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen (LANA) protein interacts with glycogen synthase kinase 3 (GSK-3) and relocalizes GSK-3 in a manner that leads to stabilization of beta-catenin and upregulation of beta-catenin-responsive cell genes. The LANA-GSK-3 interaction was further examined to determine whether there were additional downstream consequences. In the present study, the nuclear GSK-3 bound to LANA in transfected cells and in BCBL1 primary effusion lymphoma cells was found to be enriched for the inactive serine 9-phosphorylated form of GSK-3. The mechanism of inactivation of nuclear GSK-3 involved LANA recruitment of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) and the ribosomal S6 kinase 1 (RSK1). ERK1/2 and RSK1 coprecipitated with LANA, and LANA was a substrate for ERK1 in vitro. A model is proposed for the overall inactivation of nuclear GSK-3 that incorporates the previously described GSK-3 phosphorylation of LANA itself. Functional inactivation of nuclear GSK-3 was demonstrated by the ability of LANA to limit phosphorylation of the known GSK-3 substrates C/EBPbeta and C/EBPalpha. The effect of LANA-mediated ablation of C/EBP phosphorylation on differentiation was modeled in the well-characterized 3T3L1 adipogenesis system. LANA-expressing 3T3L1 cells were impaired in their ability to undergo differentiation and adipogenesis. C/EBPbeta induction followed the same time course as that seen in vector-transduced cells, but there was delayed and reduced induction of C/EBPbeta transcriptional targets in LANA-expressing cells. We conclude that LANA inactivates nuclear GSK-3 and modifies the function of proteins that are GSK-3 substrates. In the case of C/EBPs, this translates into LANA-mediated inhibition of differentiation.


Implementation of a Pig Toilet in a Nursery Pen with a Straw-Littered Lying Area.
In this study, a pig toilet was installed on an organic pig farm, which enabled pigs to use a lying area littered with straw and keep it clean. The pig toilet was separated into a defaecation area and a urination area and nursery pigs were trained to use the urination area by means of a rewarding system. A total of 24 piglets were weaned at 6-7 weeks of age and housed in the experimental system for four-week periods. Per trial, a group of four pigs was formed, and videos were recorded on two days per week (08:00 to 18:00). Direct observation was carried out in the first and last week of each trial. In total, 1500 eliminations were video-analysed. An individual pig had an average of 7.1 ± 1.4 defaecations and 4.8 ± 0.8 urinations per day. In total, 96.4% of all urinations and 97.4% of all defaecations were performed in the pig toilet. However, most urinations took place in the defaecation area as well (90.4%). Even if the training to spatially separate defecation and urination behaviour was not successful, we showed that a pig toilet offers the possibility to create littered lying areas, possibly increasing animal welfare.


Construction of viable deletion and insertion mutants of the Sabin strain of type 1 poliovirus: function of the 5' noncoding sequence in viral replication.
A number of deletion and insertion sequences were introduced into the 5' noncoding sequence (742 nucleotides long) of the genome of the Sabin strain of type 1 poliovirus by using an infectious cDNA clone of the virus strain. The genomes of all three poliovirus serotypes contained highly homologous sequences (nucleotide positions 509 to 639) as well as highly variable sequences (positions 640 to 742) in the 5' noncoding region. The viability of mutant viruses was tested by transfecting mutant cDNA clones into African green monkey kidney cells and then estimating the plaque sizes displayed on the cells. The results suggested that the highly variable sequence next to the VP4 coding region did not play an important role, at least in the in vitro culture system used, that the loci of highly conserved nucleotide sequences were not always expected to be the genome regions essential for viral replication, that the sequence between positions 564 and 599 carried genetic information to maintain the efficiency of certain steps in viral replication, and that the sequence between positions 551 to 563 might play an essential role in viral replication. Four-base deletion or insertion mutations were introduced into relatively variable sequences in the genome region upstream of position 509. The results suggest that variable sequences do not always indicate that the corresponding genome regions are less important. Apparent revertants (large-plaque variants) were easily generated from one of the viable mutants with the small-plaque phenotype. The determination of nucleotide sequences of the revertant genomes revealed the second mutation site. The results suggested that the different loci at around positions 200 and 500 might specifically interact with each other. This interaction may result in the formation of a functional structure that influences the efficiency of certain steps in the viral replication.


The Effects of Hypericum perforatum L. on the Proliferation, Osteogenic Differentiation, and Inflammatory Response of Mesenchymal Stem Cells from Different Niches.
The aim of this study is to demonstrate and compare the differentiation, proliferation, migration and inflammatory behavior of dental pulp- and bone marrow-derived mesenchymal stem cells (DP-MSCs and BM-MSCs) in response to a Hypericum perforatum ethanol extract. Using xCELLigence, a real-time monitoring system, a dose of 10 µg/mL was found to be the most efficient concentration for vitality. The IC50 values and doubling time were calculated. The results showed that H. perforatum L. was able to accelerate osteogenic differentiation in DP-MSCs, but calcium granulation was impaired in BM-MSCs. H. perforatum L.-induced migration increased when compared to the TNF-α-induced migration in a Transwell migration assay, and the IL-6 cytokine levels between cells also differed. It can be suggested that tissue memory is an important factor in MSCs, and that they differ in their response to external factors. In conclusion, H. perforatum L. can be considered an excellent osteoinductive agent for DP-MSCs but should not be used for BM-MSCs. Tissue-specific osteoinductive agents should be discussed in future studies.


Efficacy of taxol in the orpk mouse model of polycystic kidney disease.
Polycystic kidney disease (PKD) a is common disease in the human population that can lead to renal failure and death. Taxol has recently been reported to be of therapeutic benefit in the cpk mouse model of PKD. To determine whether these results also apply to other models of PKD, we studied the effects of taxol treatment on the development of renal cysts and biliary hyperplasia/dysplasia/fibrosis in the orpk mouse mutant, a unique murine model for human autosomal recessive PKD. We report no significant differences between the treatment and control groups with respect to weight gain, survival, urine to serum osmolality ratio, and serum concentration of liver enzymes. Moreover, renal cystic development was not affected by taxol treatment in the orpk mutant animals. This was confirmed by lectin staining and morphometric analysis of the renal cysts, which indicated no significant differences between treatment groups. Therefore, while taxol has a positive effect on the cystic kidney disease in cpk mutant mice, this effect is not applicable to all forms of PKD.


L-Ascorbic acid can abrogate SVCT-2-dependent cetuximab resistance mediated by mutant KRAS in human colon cancer cells.
Colon cancer patients with mutant KRAS are resistant to cetuximab, an antibody directed against the epidermal growth factor receptor, which is an effective clinical therapy for patients with wild-type KRAS. Numerous combinatorial therapies have been tested to overcome the resistance to cetuximab. However, no combinations have been found that can be used as effective therapeutic strategies. In this study, we demonstrate that L-ascorbic acid partners with cetuximab to induce killing effects, which are influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human colon cancer cells with a mutant KRAS. L-Ascorbic acid treatment of human colon cancer cells that express a mutant KRAS differentially and synergistically induced cell death with cetuximab in a SVCT-2-dependent manner. The ectopic expression of SVCT-2 induced sensitivity to L-ascorbic acid treatment in human colon cancer cells that do not express SVCT-2, whereas the knockdown of endogenous SVCT-2 induced resistance to L-ascorbic acid treatment in SVCT-2-positive cells. Moreover, tumor regression via the administration of L-ascorbic acid and cetuximab in mice bearing tumor cell xenografts corresponded to SVCT-2 protein levels. Interestingly, cell death induced by the combination of L-ascorbic acid and cetuximab resulted in both apoptotic and necrotic cell death. These cell death mechanisms were related to a disruption of the ERK pathway and were represented by the impaired activation of RAFs and the activation of the ASK-1-p38 pathway. Taken together, these results suggest that resistance to cetuximab in human colon cancer patients with a mutant KRAS can be bypassed by L-ascorbic acid in an SVCT-2-dependent manner. Furthermore, SVCT-2 in mutant KRAS colon cancer may act as a potent marker for potentiating L-ascorbic acid co-treatment with cetuximab.


[Transvesical prostatectomy].
Transvesical (open) prostatectomy is an operation method that has been performed less frequently during the last decades. Most documentation of the method is old, and few young urologists become experienced with the method. From 1994 to 2003, 66 patients underwent open prostatectomy at our department. We have reviewed all patient records retrospectively, and sent questionnaires to the patients who are still alive. . Mean operation time of patients with benign symptom-giving prostate enlargement was 88 min, blood loss during the operation was 917 mL and 50% of the patients received blood-transfusions during hospitalisation. 9% needed surgical re-intervention during the first 30 days. The time to removal of the post-operative catheter was 7.2 days and post-operative hospitalisation lasted for 8.4 days. The median weight of enucleated prostate adenomas was 107 g and carcinoma(s) were incidentally found for 4 patients (7%). 42/48 (88%) patients were content or very content with urination, when answering the questionnaires. Five patients had variable degrees of urinary incontinence after the treatment. Open prostatectomy is a complicated procedure with high rates of perioperative bleeding- and reintervention, but low rates of perioperative mortality. Most of the patients have a good long-term effect, but more patients were affected by urinary incontinence than we expected. These patients should be followed more closely.


[Completion pneumonectomy after 4 times of resections for metastatic lung tumors from rectal carcinoma].
We report a case of completion pneumonectomy after 4 times of metastasectomy for metastatic lung tumors from rectal carcinoma. A 63-year-old man underwent Miles' operation for advanced rectal carcinoma. Forty-seven months after the operation, bilateral metastasis was appeared, and bilateral metastasectomy was performed. After the resection, 3 times of metastasectomy were performed during 40 months. Follow-up X-ray and computed tomography (CT) showed abnormal shadow in his left hilum of lung. Completion pneumonectomy with mediastinal lymph node sampling was performed. He is still alive without recurrence 4 years after first thoracotomy. Repeated pulmonary resection can lead to good outcome for selective patients with metastatic colorectal carcinoma, and repeated surgery can be useful for pulmonary recurrences after thoracotomy.


Can We Finally Move the Needle on Diversity, Equity, and Inclusion in Nursing?
Much attention has been given to diversity, equity, and inclusion in health care for more than a decade. This has resulted in slow progression in moving the needle. Minority nurses continue to be unrepresented and express higher levels of dissatisfaction in comparison with their White counterparts. Minority nurses report significantly higher odds of being dissatisfied with their independence at work, advancement opportunities, salary, and tuition benefits. This article provides a context for minority nurse underrepresentation and dissatisfaction and suggests actionable interventions to make nursing more inclusive.


The changes of alpha-amylase activity in serum and different tissues of female rat during sex cycle--isoelectrofocusing studies of alpha-amylase.
It has been suggested that hormonal changes may influence alpha-amylase activity during sex cycle. The aim of this study was to evaluate these changes in serum and different tissues during sex cycle in female rats. The animals were assigned to proestrus, estrus, and diestrus groups depending on vaginal smears. We measured the activities of alpha-amylase in the serum, liver, salivary glands, pancreas and ovary of female rats, serum level of calcium, rat luteinising hormone (rLH) and rat follicle stimulating hormone (rFSH). The serum and tissue amylases were also characterized by wide-range polyacrylamide gel isoelectrofocusing. Statistically significant changes of alpha-amylase activity were found only in the ovary. The activity of alpha-amylase raised from proestrus (mean 303 +/- 124 IU/g) through estrus (mean 157 +/- 123 IU/g) and declined in diestrus (mean 81.9 +/- 51.6 IU/g). There were no statistically significant changes in the serum, liver, salivary glands and pancreas. We found two isoenzymes of alpha-amylase: one peak of amylase, present in the serum, liver, salivary gland and ovary with the mean isoelectric point of ca 5.34 and another present in ovary and pancreas with mean isoelectric point of ca 8.32. The only tissue found to contain both isoamylases was the ovary. We did not find any correlation between serum calcium level and alpha-amylase activity in the serum and ovary. The pattern of changes of alpha-amylase activity does not depend on the type of isoamylase in the tissue, but probably on the tissue influenced by the sex cycle. The changes of alpha-amylase activity are not mediated by calcium, they seem to result primarily from the profile of sex hormones affecting directly the target tissues.


Dystrophy-associated caveolin-3 mutations reveal that caveolae couple IL6/STAT3 signaling with mechanosensing in human muscle cells.
Caveolin-3 is the major structural protein of caveolae in muscle. Mutations in the CAV3 gene cause different types of myopathies with altered membrane integrity and repair, expression of muscle proteins, and regulation of signaling pathways. We show here that myotubes from patients bearing the CAV3 P28L and R26Q mutations present a dramatic decrease of caveolae at the plasma membrane, resulting in abnormal response to mechanical stress. Mutant myotubes are unable to buffer the increase in membrane tension induced by mechanical stress. This results in impaired regulation of the IL6/STAT3 signaling pathway leading to its constitutive hyperactivation and increased expression of muscle genes. These defects are fully reversed by reassembling functional caveolae through expression of caveolin-3. Our study reveals that under mechanical stress the regulation of mechanoprotection by caveolae is directly coupled with the regulation of IL6/STAT3 signaling in muscle cells and that this regulation is absent in Cav3-associated dystrophic patients.


Sesquiterpene Backbones Generated by Sesquiterpene Cyclases: Formation of iso-Caryolan-1-ol and an Isoclovane.
New sesquiterpene backbones are accessible after incubation of caryolan-synthase (GcoA) and presilphiperfolan-8-β-ol synthase (BcBOT2) with a non-natural farnesyldiphosphate in which the central olefinic double bond is isomerized toward the methyl group. Two newly formed sesquiterpenoids are reported, a constitutional isomer of caryolan-1-ol (3), which we name iso-caryolan-1-ol (17), and the first terpenoid based on the isoclovane ring skeleton generated enzymatically thus far.


Severe acute respiratory syndrome--retrospect and lessons of 2004 outbreak in China.
To summarize lessons learned from an outbreak of severe acute respiratory syndrome (SARS) in China during the spring of 2004. Data of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention (BCDC) and Anhui Provincial Center for Disease Control and Prevention (APCDC) and results of epidemiological investigations were collected and analyzed. Three generations of 11 cases of SARS were identified during the outbreak. Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients. Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases. SARS outbreak in 2004 has yielded following lessons for public health globally. (1) Lab bio-safety programs should be made and should be strictly abided by. Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious. (2) Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.


An evidence-based review of NX1207 and its potential in the treatment of benign prostatic hyperplasia.
In elderly men, benign prostatic hyperplasia is often associated with lower urinary tract symptoms, and its prevalence rises with age. Lower urinary tract symptoms can be very bothersome and lead to a decrease in health-related quality of life. Furthermore, benign prostatic hyperplasia is a progressive disease that can lead to serious complications like acute urinary retention. Medical treatment with α1-blockers or 5α-reductase inhibitors is recommended by the European Association of Urology. On the other hand, there are some new innovations such as NX1207. The aim of this review is to summarize the published data. NX1207 is a new drug that is administered by transrectal intraprostatic injection under ultrasound guidance. The substance leads to prostate volume reduction and symptomatic improvement. However, patient numbers are still low and currently treatment with NX1207 is still experimental.


A novel TCTP gene from the crustacean Eriocheir sinensis: possible role involving metallic Cu2+ stress.
The translationally controlled tumor protein (TCTP), which was initially described as a growth-related protein, primarily expresses proteins for numerous biological processes in eukaryotes. In the present study, the TCTP gene in the Chinese mitten crab Eriocheir sinensis (Es-TCTP) was identified from tissues of the hepatopancreas, by the construction of a cDNA library and the rapid amplification of cDNA ends. The results showed that the full length of Es-TCTP cDNA comprises 727 nucleotides, with an open reading frame of 507 bp that encodes 168 amino acid residues. The deduced amino acid sequence of Es-TCTP has a 51%-92% similarity to TCTPs of other eukaryotic species. The mRNA transcripts of Es-TCTP were detected by using RT-PCR for all tissues, with the highest level occurring in the hepatopancreas. In addition, temporal expression of the Es-TCTP was measured to analyze the role of Es-TCTP in an acute stress condition after CuSO(4) treatment. The expression of the Es-TCTP transcripts in hepatopancreas had no significant difference at the first 4 h, but increased significantly after 8 h, peaked at 24 h (4.3-fold higher than the control), and was still high after 72 h. Our results indicate that Es-TCTP is an acute-phase protein that is involved in Cu(2+) stress, with a possible anti-stress function in invertebrates.


Surgery performed by supervised registrars does not adversely affect medium-term functional outcomes after total knee replacement.
Introduction Although total knee arthroplasty (TKA) is an index procedure for orthopaedic registrars, there is a lack of published research as to the effects of surgery when performed by supervised trainees. The aim of this study was to compare functional outcomes up to five years after primary TKA performed by consultants and trainee surgeons. Methods A retrospective analysis was conducted of prospectively collected data for 609 consecutive patients (339 female, 270 male) undergoing TKA. Patients were assessed preoperatively as well as at 18 months, three years and five years postoperatively, and American Knee Society objective knee and functional scores (AKSK and AKSF) were recorded. Results Surgery was performed by a consultant in 465 cases and a supervised trainee in 144 cases. There were no significant differences between the two groups in preoperative patient characteristics, operative time (p=0.15), transfusion rates (p=0.84), length of stay (p=0.98), manipulation under anaesthesia (p=0.69), or mortality rates at one year (p=0.73) or five years (p=0.81). Postoperatively, the median magnitude of improvement in AKSK (48 points for consultant group vs 45 points for trainee group, p=0.74) and in AKSF (both groups 15, p=0.995) was similar between the groups. AKSK and AKSF scores were similar at all timepoints up to five years following surgery, and there was no difference in the median range of motion (both groups 100°, IQR: 18°) at five years (p=0.43). Conclusions TKA performed by supervised registrars gives functional outcomes that are equivalent to consultant performed TKA, without affecting postoperative range of movement, or increasing operative time, length of stay or transfusion rates. Rates of postoperative MUA and mortality are also comparable.


The longitudinal effect of the quality of participation experiences in a voluntary organization on youth psychological empowerment.
Research shows its limitations by not capturing the specificities of individual experiences, which result either from the participation of or interaction among different people in a given context across time. This study explores the effect that the quality of youth participation experiences in a Portuguese voluntary organization can have on the development of their psychological empowerment (PE). This study adopted a longitudinal, quantitative design where the same cohort of 481 participants (62.4% female; Mage = 17.26 years) was followed across three time points. Latent growth curve modeling was performed to examine the effect of the quality of participation experiences (QPE) on the developmental trajectories of PE components. Findings show that the QPE had the most powerful effect on developmental trajectories in PE. The study shows how youth perceptions of opportunities for reflection and action in interaction in a climate of openness to dialogue and the emergence of different ways of thinking and doing affect their PE.


Clinical Analysis of Recurrence Patterns in Patients With Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy.
To evaluate the characteristics and risk factors for locoregional recurrence in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). The clinical diagnosis and treatment data of 195 patients with NPC treated with IMRT from March 2005 to May 2010 (including 9, 24, 70, and 92 cases of stage I, II, III, and IV disease, respectively, according to the 7th edition American Joint Committee on Cancer staging criteria) were retrospectively analyzed. The Kaplan-Meier method was used for survival analysis, and logistic regression was used to conduct univariate and multivariate analyses. The 5-year recurrence rate was 10.8%, and the 5-year local and regional recurrence rates were 8.7% and 3.4%, respectively. Multivariate analysis showed that the short axis of the cervical lymph nodes (≥3 cm) was an influencing factor for regional lymph node recurrence after IMRT. In-field and high-dose region failures were the main patterns associated with local-regional recurrence, and nasopharyngeal recurrence was most commonly detected. Newly diagnosed patients with large cervical lymph nodes (short diameter ≥3 cm) should be carefully followed up considering regional lymph node recurrence.


A prospective study of sexual and urinary function before and after total mesorectal excision with autonomic nerve preservation for rectal cancer.
Oncologic resection of rectal cancer has been reported to be associated with a significant (10%-60%) rate of sexual and urinary dysfunction. We hypothesize that curative total mesorectal excision (TME) with autonomic nerve preservation (ANP) can be done with high rates of preservation of such function. We studied prospectively preoperative and postoperative urinary and sexual function in patients who had sphincter-preserving operations for rectal carcinoma without preoperative irradiation. Standardized questionnaires were used preoperatively and postoperatively, including the International Prostatic Symptom Score and a score of quality of urinary function satisfaction. Urodynamic evaluation was performed preoperatively and 3 months after the operation. The sexual results were evaluated after 1 year. Twenty patients, 13 men and 7 women, had TME, with ANP technique. Fourteen patients had coloanal anastomosis, 4 had a stapled colorectal anastomosis, and 2 had an ileoanal anastomosis. In all patients, hypogastric and sacral splanchnic nerves were identified and preserved. There was no mortality. Tumors are graded by Astler-Coller classification: A1 in 3 cases, A2 in 3, B1 in 7, B2 in 2, C2 in 1, and D in 1. There was no difference in preoperative and postoperative urinary function, International Prostatic Symptom Score, or urodynamic results, nor in the results of the quality of urinary function questionnaire. Four of the 7 women (69%) were sexually active before undergoing the surgical procedure. Sexual activity and ability to achieve orgasm was unchanged in these women. No dyspareunia was reported. Nine of the 13 men (69%) were sexually potent in the preoperative period. Sexual activity and potency were unchanged in these men. Retrograde ejaculation was reported in 1 man who previously had had normal antegrade ejaculation. After 3 months, 4 patients reported a reduced rigidity of erection, returning to normal by 1 year. The authors conclude that TME and ANP for cancer limited to the mesorectum do not impair urinary and sexual function.


Delayed effect of radiation therapy with or without chemotherapy on ovarian function in women with Hodgkin's disease.
In this retrospective investigation of 51 female patients with Hodgkin's disease, the age of the patient at the time of primary treatment and the extent of radiation therapy were the two most important factors determining post-therapy ovarian function. Favourable indicators of ovarian preservation included young age, especially premenarchal , at the time of primary therapy, and irradiation confined to above the pelvic brim, whereas, age over 40 and irradiation below the pelvic brim predicted high probability of ovarian failure. Overall, 55 per cent of female patients under the age of 50 treated with chemotherapy alone or with radiation therapy above the pelvic brim retained normal ovarian function. The stage of disease at presentation and the post-therapy status of disease had no apparent effect on subsequent menstrual function.


The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients.
Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. Greater hope was significantly related to a steeper cortisol slope, β = -0.193, p = 0.046, and lower night cortisol, β = -0.227, p = 0.018, plasma IL-6, β = -0.142, p = 0.033, and ascites IL-6, β = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol β = -0.233,p = 0.017 and ascites IL-6, β = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, β = 0.211, p = 0.031. These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.


Impact of an annual dollar limit or "cap" on prescription drug benefits for Medicare patients.
Annual dollar limits, or "caps," on drug benefits are common in Medicare managed care (Medicare + Choice) and have been part of several proposals for a national Medicare drug benefit. To determine how cap levels affect the percentage of patients exceeding the cap and their out-of-pocket drug costs and to identify the medications that contribute most to prescription costs. Cross-sectional analysis of 2001 pharmacy claims data from a large Medicare + Choice plan in a mature market with caps of 750 dollars to 2000 dollars per year applied to the plan's share of prescription costs. Patients who filled at least 1 prescription in 2001 (n = 438 802). Percentages of patients exceeding caps, identified from prescription claims; out-of-pocket patient costs before exceeding caps, calculated from patients' co-payments; and out-of-pocket patient costs after exceeding caps, estimated from total prescription costs before exceeding the cap. Each unique drug was ranked by total expenditures, which included spending by patients who exceeded caps and by the plan for that drug. A total of 22%, 14%, and 4% of Medicare patients exceeded caps of 750 dollars, 1000 dollars, and 2000 dollars, respectively. Across caps, patients faced a potential 2- to 3-fold increase in median out-of-pocket costs after exceeding caps (179 dollars-305/mo dollars) to continue the same prescription use as before exceeding caps (79-100/mo dollars). For patients who exceeded a cap of 750 dollars, yearly out-of-pocket drug costs ranged from 564 dollars to 4201 dollars (5th-95th percentiles). Fifteen of the 20 medications with the highest total prescription expenditures for patients who exceeded the cap were for chronic conditions. Seven had lower-cost generic versions or a generic medication available in the same treatment class. At lower caps, a substantial proportion of Medicare patients exceeded their annual drug benefit. To continue the same medication use as before exceeding caps, these patients faced potentially high increases in out-of-pocket costs for medications used primarily to treat chronic conditions. Generic options were not available for many of these drugs.


Horizontal gene transfer from Agrobacterium to plants.
Most genetic engineering of plants uses Agrobacterium mediated transformation to introduce novel gene content. In nature, insertion of T-DNA in the plant genome and its subsequent transfer via sexual reproduction has been shown in several species in the genera Nicotiana and Linaria. In these natural examples of horizontal gene transfer from Agrobacterium to plants, the T-DNA donor is assumed to be a mikimopine strain of A. rhizogenes. A sequence homologous to the T-DNA of the Ri plasmid of Agrobacterium rhizogenes was found in the genome of untransformed Nicotiana glauca about 30 years ago, and was named "cellular T-DNA" (cT-DNA). It represents an imperfect inverted repeat and contains homologs of several T-DNA oncogenes (NgrolB, NgrolC, NgORF13, NgORF14) and an opine synthesis gene (Ngmis). A similar cT-DNA has also been found in other species of the genus Nicotiana. These presumably ancient homologs of T-DNA genes are still expressed, indicating that they may play a role in the evolution of these plants. Recently T-DNA has been detected and characterized in Linaria vulgaris and L. dalmatica. In Linaria vulgaris the cT-DNA is present in two copies and organized as a tandem imperfect direct repeat, containing LvORF2, LvORF3, LvORF8, LvrolA, LvrolB, LvrolC, LvORF13, LvORF14, and the Lvmis genes. All L. vulgaris and L. dalmatica plants screened contained the same T-DNA oncogenes and the mis gene. Evidence suggests that there were several independent T-DNA integration events into the genomes of these plant genera. We speculate that ancient plants transformed by A. rhizogenes might have acquired a selective advantage in competition with the parental species. Thus, the events of T-DNA insertion in the plant genome might have affected their evolution, resulting in the creation of new plant species. In this review we focus on the structure and functions of cT-DNA in Linaria and Nicotiana and discuss their possible evolutionary role.


First report of hare treponematosis seroprevalence of European brown hares (Lepus europaeus) in the Czech Republic: seroprevalence negatively correlates with altitude of sampling areas.
The aim of this study was to quantify the seroprevalence of hare treponematosis in European brown hare (Lepus europaeus) populations in the Czech Republic and to test for an association between treponematosis prevalence and the altitude of the areas in which hares were sampled. We tested 289 serum samples of brown hares collected between 2015 and 2017. The sampling areas included 12 districts (73 villages) distributed throughout the Czech Republic. Serum samples were tested for the presence of antibodies against the causative agent of hare treponematosis (Treponema paraluisleporidarum ecovar Lepus, TPeL) using two serological tests for human syphilis that cross-react with TPeL: the Treponema pallidum hemagglutination assay (TPHA) and the fluorescent treponemal antibody absorption (FTA-ABS) test. To account for the imperfect diagnostic sensitivity and specificity of each test, apparent prevalence estimates of TPeL were converted to true prevalence estimates using the Rogan Gladen estimator. The correlation between TPeL true seroprevalence and altitude of sampling areas was analyzed using Pearson's correlation coefficient at three levels of spatial resolution: (1) four groups, each composed of two merged districts, with ≥20 samples collected, differing in their altitude median (206, 348, 495, and 522 m above sea level); (2) separately tested eight districts, where ≥20 samples were collected per district; and (3) 27 groups composed of villages of the same altitude level distributed across the whole dataset. One hundred and seven of the 289 samples were seropositive to both tests, the FTA-ABS test was positive for an additional 47 samples. Seropositive samples were found in all 12 districts. True seroprevalence of TPeL in the sampled hares was 52% (95% confidence interval 46 to 58%). A statistically significant negative correlation between TPeL seroprevalence and altitude was identified at the district level (Pearson's r = - 0.722, p = 0.043). Between 2015 and 2017 hare treponematosis was present at a relatively high prevalence in brown hares in all 12 districts in the Czech Republic where sampling was carried out. The seroprevalence of TPeL in brown hares was negatively correlated with the altitude of the areas in which hares were sampled.


Exact and Asymptotic Weighted Logrank Tests for Interval Censored Data: The interval R package.
For right-censored data perhaps the most commonly used tests are weighted logrank tests, such as the logrank and Wilcoxon-type tests. In this paper we review several generalizations of those weighted logrank tests to interval-censored data and present an R package, interval, to implement many of them. The interval package depends on the perm package, also presented here, which performs exact and asymptotic linear permutation tests. The perm package performs many of the tests included in the already available coin package, and provides an independent validation of coin. We review analysis methods for interval-censored data, and we describe and show how to use the interval and perm packages.


Calculating the distribution of ventilation-perfusion ratios from inert gas elimination data.
It is well known that the major cause of hypoxemia in lung disease is ventilation-perfusion (VA/Q) inequality, but it has been extremely difficult to measure the distribution of ventilation-perfusion ratios except in terms of unrealistically simple (albeit useful) models. The multiple inert gas elimination technique provides considerable information concerning the shape, position, and dispersion of the VA/Q distribution, although it cannot precisely define all features of the distribution. Although there are many techniques for obtaining information about the distribution from inert gas elimination data, we have found the most flexible and useful approach to be a multicomponent analysis with enforced smoothing, sometimes known as ridge regression. This presentation describes in some detail the physiological and mathematical principles principles involved in the transformation of inert gas elimination data into a representative distribution of ventilation-perfusion ratios by enforced smoothing techniques. It is important to realize that with this approach and any other approach aimed at estimating the distribution of ventilation-perfusion ratios, the results must be properly interpreted.


Calcium sources and their interaction with the different levels of non-phytate phosphorus affect performance and bone mineralization in broiler chickens.
An experiment was conducted to evaluate the influence of different Ca sources (limestone, Ca chloride, and Lipocal, a fat-encapsulated tricalcium phosphate, TCP) in conjunction with 4 dietary levels of non-phytate P (NPP) on performance, ileal digestibility of Ca and P, and bone mineralization in broiler chickens. Calcium sources were also evaluated in vitro to measure acid-binding capacity (ABC) and Ca solubility at different pH values. Ca chloride showed the highest solubility of Ca, with TCP showing the highest ABC. Ross male broiler-chicks were sorted by BW at 1 d post-hatch and assigned to 5 cages per diet with 5 birds per cage. Twelve diets were arranged in a 3×4 factorial of the 3 Ca sources and 4 levels of NPP (0.3%, 0.35%, 0.4% or 0.45%) consisting of 4 added P levels (Ca(H2PO4)2) with a high dose of phytase (1,150 U/kg) in all diets. On d 14 post-hatch, 3 birds were euthanized, and ileal digesta and the right tibia were collected to determine ileal Ca and P digestibility and bone mineralization, respectively. Feed intake (FI) and weight gain (WG) on d 14 was higher (P<0.01) with TCP and limestone than with Ca chloride. Added P increased the tibia weight and tibia ash content in chicks fed TCP up to 0.4% NPP and limestone up to 0.35% NPP. Calcium ileal digestibility was higher (P<0.01) with Ca chloride (73.7%) than with limestone (67.1%) or TCP (66.8%), which increased (P<0.05) with added levels of P from monocalcium phosphate. Phosphorus ileal digestibility was not affected by the Ca source and increased (P<0.001) with added levels of NPP. It can be concluded that starting broilers responded better to low-soluble Ca sources compared to high-soluble sources. A level of 0.35%-0.40% NPP with a high dose of phytase (1,150 U/kg) in diets including limestone or TCP is sufficient to guarantee performance and bone formation for broiler chickens from d 0 to d 14.


Chiropractic concepts of the short leg: a critical review.
There have been relatively few subject areas within the chiropractic profession which have led to such widespread misunderstanding, confusion and controversy. This paper will attempt to examine the research surrounding the development of our current state of understanding concerning the many factors affecting the short leg. Traditionally, research surrounding the short leg has moved in several discreet directions. The first has been toward determining a reliable radiographic method used for measuring structural short legs. Many papers have been published here; included would be the work of Heufelder, Farinet, Giles, Nylander, Manganiello, Marstander, Wettstein, Schilgen and many others. Most tend to center upon use of new instrumentation or use of precise radiographic methods, usually involving femoral head views in some form or other. Another direction the research has taken is into an examination of how the presence of short leg affects biomechanics in both stance and ambulation. Further, investigation here have also centered upon how short leg may alter spinal growth and growth of other bones. I would include here the work of Giles, Pokorna, Moseley, Shapiro, Freiburghaus and Friberg. Other areas of research include diagnosis, therapy and correction. I leave for last a discussion on reliability studies. A major tenant of some chiropractic therapies involves the use of measurement of "functional" short leg. Though procedures for making such measurement are in the public domain, there is no proof within the literature that such exists. There have been done reliability studies attempting to show repeatability of measurement. Results have been mixed at best. I would note here the work of De Boer, Venn and Wakefield, Nichols and others. In all, this is an area under rapid and fairly extensive examination, with a wealth of previous papers available for perusal.


Dental Care: Unmet Oral Needs of Patients With Cancer and Survivors .
Oral and dental side effects of cancer treatment can be painful, impede function, and affect patients' quality of life. Inclusion of the dental team is important prior to, during, and after treatment to manage temporary, chronic, or permanent sequelae of treatment. Separation of medical and dental specialties and models of insurance reimbursement make obtaining medically necessary dental care unduly difficult. Nurses are at the front line of care and in a position to identify oral side effects of treatment, provide education, and advocate for proper dental care. .


The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting.
Macrophage migration inhibitory factor (MIF) is a mediator of host immunity and functions as a high, upstream activator of cells within the innate and the adaptive immunological systems. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. To better understand MIF's activity in growth control, we generated and characterized a strain of MIF-knockout (MIF-KO) mice in the inbred, C57BL/6 background. Embryonic fibroblasts from MIF-KO mice exhibit p53-dependent growth alterations, increased p53 transcriptional activity, and resistance to ras-mediated transformation. Concurrent deletion of the p53 gene in vivo reversed the observed phenotype of cells deficient in MIF. In vivo studies showed that fibrosarcomas induced by the carcinogen benzo[alpha]pyrene are smaller in size and have a lower mitotic index in MIF-KO mice relative to their WT counterparts. The data provide direct genetic evidence for a functional link between MIF and the p53 tumor suppressor and indicate an important and previously unappreciated role for MIF in carcinogenesis.


Evolution of bunyaviruses by genome reassortment in dually infected mosquitoes (Aedes triseriatus).
Aedes triseriatus mosquitoes became dually infected after ingesting two mutants of LaCrosse (LAC) virus simultaneously or after ingesting, by interrupted feeding, the two viruses sequentially within a 2-day period. After 2 weeks of incubation, approximately 25 percent of the vectors contained new virus genotypes as the result of RNA segment reassortment. New viruses were transmitted when the mosquitoes fed on mice. Viruses ingested more than 2 days after the initial infecting virus did not cause superinfection of the mosquito vectors.


Current trends in clinical research on panic attacks, agoraphobia, and related anxiety disorders.
In recent years, anxiety research has increased in pace. An important trend has been the distinction between panic anxiety and generalized anxiety, which is reflected in the DSM-III classification. This paper reviews the evidence in favor of this diagnostic distinction and explores the linkage between panic anxiety and agoraphobia.


Attitudes towards mental illness. A review of the literature.
With the advent of community psychiatry, the pressure of care of the mentally ill will increasingly fall on the family and the community. In order for this transition to succeed, it is important to bear in mind the attitudes of the community and the caregivers. This article reviews the literature on public attitudes and suggestions are made for future research and lessons to be learnt from the experience in North America.


Evaluation of decision rules for frequency-doubling technology screening tests.
Frequency-doubling technology (FDT) perimetry has shown promise as a screening test for glaucoma. This study investigates different possible decision rules for FDT screening by applying them to groups of normal and glaucoma subjects. Within three centers, 218 subjects (aged 15-88 years; 78 with glaucoma, 140 without ocular disease) were each tested twice with the screening program of the FDT perimeter. The subjects consisted of 140 normal subjects with no evidence of glaucoma or other ocular disease likely to affect the visual field and 78 subjects with a diagnosis of glaucoma and no other ocular disease. Fifteen decision rules were applied to the data to compare their sensitivity and specificity. Estimated specificities of the different decision rules ranged from 78% to 99%, although with this sample size, the confidence intervals for these estimates are quite large. Estimated sensitivities ranged from 40% to 72%. Suggested criteria for distinguishing normal subjects from those with glaucoma seem to be either a cluster of two or more adjacent locations abnormal at the p < 2% level with at least one location confirmed or a single location very abnormal (p < 1%) and confirmed. Specificity was clearly improved by confirming an apparently abnormal test result by repeating the screening test outweighing the resultant small loss in sensitivity. These findings provide useful information for making an informed choice of decision rules for FDT screening results.


Piriformis and obturator internus morphology: a cadaveric study.
Preservation of piriformis during exposure of the hip joint via a posterior approach may result in a lower rate of dislocation following total hip arthroplasty. The aim of this study was to identify anatomical variations in the tendons of piriformis and obturator internus which could inform piriformis sparing approaches to the hip. Twenty-nine proximal femora from 15 cadavers, 5 male and 10 female aged 65-79 years, were examined. Tendon crossing angles, location and mode of insertion to the greater trochanter and the extent of fusion between tendons prior to insertion were noted. The mean (and associated standard deviation) of the vertical and horizontal widths of the piriformis tendon were 4.78 ± 1.31 mm and 7.35 ± 1.74 mm, respectively. The mean (and associated standard deviation) of the vertical and horizontal widths of the obturator internus tendon were 6.87 ± 1.61 mm and 5.72 ± 1.38 mm, respectively. The mean distances of the anterior and posterior margins of the piriformis tendon insertion from the posterior limit of the greater trochanter, defined as a percentage of the anteroposterior length of the greater trochanter, were 63.3% ± 9.4% and 43.0% ± 9.4%, respectively. Equivalent mean distances for the obturator internus insertion were 73.0% ± 6.6% and 55.9% ± 7.0%, respectively. On the basis of the relationship between the piriformis and obturator internus tendons in terms of the angle and point at which they cross, in addition to any degree of tendon fusion, four classifications were identified. This study shows that the most posterior margins of the piriformis and obturator internus attachments are located more than one-third of the way along the greater trochanter, suggesting that current osteotomies would not include these external rotators in the majority of cases.


The level of evidence keeps improving: An updated analysis of the scientific program at the Canadian Association of Paediatric Surgeons Annual Meeting.
The purpose of this study is to examine the scientific program of the Canadian Association of Pediatric Surgeons (CAPS) to determine if the quality of research has improved. CAPS abstracts from 2010 to 2013 were reviewed by two independent researchers. Presentation type, study design, and level of evidence (LOE) were recorded. All differences were adjudicated by an epidemiologist. Fisher's exact test compared results to a previous study that assessed LOE in CAPS abstracts from 2005 to 2009. 291 abstracts were reviewed with 53 excluded and 238 included in final analysis. Reviewers demonstrated high agreement for study design (ICC=0.767 95%CI 0.715-0.810) and LOE (ICC=0.914 95%CI 0.892-0.931). Out of 238 studies, 117 (49%) were podium and 122 (51%) posters. Number of high-quality studies increased in 2010-2013 versus 2005-2009 (n=253), specifically systematic reviews (n=15 (6%) vs. n=3 (1%) p<0.01), randomized controlled trials (n=4 (2%) vs. n=0 (0%), p=0.05), and prospective cohort studies (n=41 (17%) vs. n=26 (10%), p<0.001). Retrospective cohort is still the most common. However, the number of studies has significantly decreased (n=121 (51%) vs. n=171 (68%), p<0.001). The proportion of high-level studies (LOE 2 or better) also improved (48 (20%) vs. 24 (10%) p<0.001). The quality of research presented at CAPS has greatly improved, especially in the past five years.


Preschool hyperactivity is associated with long-term economic burden: evidence from a longitudinal health economic analysis of costs incurred across childhood, adolescence and young adulthood.
Preschool hyperactivity is an early risk factor for adult mental health problems and criminality. Little is known about; (a) the patterns of long-term service costs associated with this behavioural marker in the general population and (b) the specific factors predicting hyperactivity-related costs. We undertook a prospective study investigating associations between preschool hyperactivity and average individual annual service costs up to late adolescent and young adulthood. One-hundred and seventy individuals rated as hyperactive by their parents and 88 nonhyperactive controls were identified from a community sample of 4,215 three years olds. Baseline information about behaviour/emotional problems and background characteristics were collected. At follow-up (when individuals were aged between 14 and 25 years) information was obtained on service use, and associated costs since the age of three. Based on this information we calculated the average cost per annum incurred by each individual. Compared to controls, preschoolers with hyperactivity had 17.6 times higher average costs per annum across domains (apart from nonmental health costs). These were £562 for each hyperactive individual compared with £30 for controls. Average annual costs decreased as a function of age, with higher costs incurred at younger ages. The effects of hyperactivity remained significant when other baseline factors were added to the model. Effects were fully mediated by later psychiatric morbidity. When the hyperactive group were examined separately, costs were consistently predicted by male gender and, for some cost codes, by conduct problems. Preventative approaches targeting early hyperactivity may be of value. Services should be targeted towards high-risk individuals with careful consideration given to the cost-to-benefit trade-off of early intervention strategies.


Cigarette smoke exposure promotes differentiation of CD4+ T cells toward Th17 cells by CD40-CD40L costimulatory pathway in mice.
This study aimed to investigate the impact of cigarette smoke exposure upon CD40-CD40L ligation between bone marrow-derived dendritic cells (BMDCs)and CD4+T cells, and to examine the effects of cigarette smoke exposure upon differentiation of CD4+T cells toward Th17 cells through blockade of CD40-CD40L pathway in mice. The study was processed in vivo and in vitro. In vivo, Th17 cells, CD40, interleukin (IL)-17A, and IL-27 in the lung tissues were quantified and compared between mice with and without cigarette smoke exposure. In vitro, Th17 cells, IL-17A, and IL-27 yielded by multiple cell cultivations in which BMDCs from mice with or without cigarette smoke exposure were fostered with CD4+ T cells from healthy mice spleens in the presence of antagonistic CD40 antibody and/or cigarette smoke extract (CSE) were quantified and compared. The flow cytometry was used to detect expressions of Th17 cells and CD40, and the liquid chip was used to detect levels of IL-17A and IL-27. Both in vivo exposed to cigarette smoke and in vitro to CSE, CD40 expressions noticeably escalated on the surfaces of BMDCs. The presence of Th17 cells, IL-17A, and IL-27 in the lung tissues prominently increased in mice exposed to cigarette smoke. The in vitro culture of CD4+ T cells and BMDCs significantly enhanced the differentiation of CD4+ T cells toward Th17 cells and secretions of IL-17A and IL-27 in the case that BMDCs were produced from mice exposed to cigarette smoke or the culture occurred in the presence of CSE. Usage of antagonistic CD40 antibody evidently reduced the number of Th17 cells, IL-17A, and IL-27 that increased due to cigarette smoke exposure. The CD40-CD40L ligation is associated with the quantities of Th17 cells and relevant cytokines in the context of cigarette smoke exposure. Reducing the number of Th17 cells via the usage of antagonistic CD40 antibody can be an inspiration for pursuing a novel therapeutic target for immune inflammation in COPD.


Kidney cancer mortality in The Netherlands, 1950-94: prediction of a decreasing trend.
Incidence and mortality rates of kidney cancer are known to be increasing world-wide. The reasons for these increases are not clear, but despite this it may still be possible to predict changes in the trend of occurrence. Male and female kidney (plus ureter and urethra) cancer mortality per 10(5) person-years, from 1950 to 94, were calculated using national demographic and mortality data. Changes in the age structure of the Dutch population were adjusted using direct standardisation to the European standard population. The effects of age, calendar period and birth cohort on the temporal trend in mortality were evaluated using log-linear modelling. Male mortality from kidney cancer increased from three per 10(5) person-years in the 1950s to eight per 10(5) in the mid 1980s and remained relatively stable thereafter. Female mortality rates showed a comparable trend, from two per 10(5) in the 1950s to four per 10(5) in the 1980s. In addition to the effects of age, the temporal trend in males can be sufficiently explained as a birth cohort effect. Successive birth cohorts appear to have higher risks of dying from kidney cancer until the 1930 cohort. The younger birth cohorts appear to have lower risks. The trend in women is comparable to that in men but is less pronounced and shows only after excluding women under the age of 45. The decreasing risk for generations born after 1930 will probably result in a decreasing trend in kidney cancer mortality in the near future. It is suggested that at least part of this changing trend in men (but not in women) is caused by the changing smoking behaviour of the Dutch population.


Twinned crystals and anomalous phasing.
Merohedral or pseudomerohedral twinning of crystals cannot be identified from inspection of the diffraction patterns. Several methods for the identification of twinning and the estimation of the twin fraction are suitable for macromolecular crystals and all are based on the statistical properties of the measured diffraction intensities. If the crystal twin fraction is estimated and is not too close to 0.5, the diffraction data can be detwinned; that is, related to the individual crystal specimen. However, the detwinning procedure invariably introduces additional inaccuracies to the estimated intensities, which substantially increase when the twin fraction approaches 0.5. In some cases, a crystal structure can be solved with the original twinned data by standard techniques such as molecular replacement, multiple isomorphous replacement or multiwavelength anomalous diffraction. Test calculations on data collected from a twinned crystal of gpD, the bacteriophage lambda capsid protein, show that the single-wavelength anomalous diffraction (SAD) method can be used to solve its structure even if the data set corresponds to a perfectly twinned crystal with a twin fraction of 0.5.


Rheology and dynamics of colloidal superballs.
Recent advances in colloidal synthesis make it possible to generate a wide array of precisely controlled, non-spherical particles. This provides a unique opportunity to probe the role that particle shape plays in the dynamics of colloidal suspensions, particularly at higher volume fractions, where particle interactions are important. We examine the role of particle shape by characterizing both the bulk rheology and micro-scale diffusion in a suspension of pseudo-cubic silica superballs. Working with these well-characterized shaped colloids, we can disentangle shape effects in the hydrodynamics of isolated particles from shape-mediated particle interactions. We find that the hydrodynamic properties of isolated superballs are marginally different from comparably sized hard spheres. However, shape-mediated interactions modify the suspension microstructure, leading to significant differences in the self-diffusion of the superballs. While this excluded volume interaction can be captured with a rescaling of the superball volume fraction, we observe qualitative differences in the shear thickening behavior of moderately concentrated superball suspensions that defy simple rescaling onto hard sphere results. This study helps to define the unknowns associated with the effects of shape on the rheology and dynamics of colloidal solutions.


Anaerobic oxidation of methane in sediments of Lake Constance, an oligotrophic freshwater lake.
Anaerobic oxidation of methane (AOM) with sulfate as terminal electron acceptor has been reported for various environments, including freshwater habitats, and also, nitrate and nitrite were recently shown to act as electron acceptors for methane oxidation in eutrophic freshwater habitats. Radiotracer experiments with sediment material of Lake Constance, an oligotrophic freshwater lake, were performed to follow 14CO2 formation from 14CH4 in sediment incubations in the presence of different electron acceptors, namely, nitrate, nitrite, sulfate, or oxygen. Whereas 14CO2 formation without and with sulfate addition was negligible, addition of nitrate increased 14CO2 formation significantly, suggesting that AOM could be coupled to denitrification. Nonetheless, denitrification-dependent AOM rates remained at least 1 order of magnitude lower than rates of aerobic methane oxidation. Using molecular techniques, putative denitrifying methanotrophs belonging to the NC10 phylum were detected on the basis of the pmoA and 16S rRNA gene sequences. These findings show that sulfate-dependent AOM was insignificant in Lake constant sediments. However, AOM can also be coupled to denitrification in this oligotrophic freshwater habitat, providing first indications that this might be a widespread process that plays an important role in mitigating methane emissions.


The U6 snRNA m6A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention.
Maintenance of proper levels of the methyl donor S-adenosylmethionine (SAM) is critical for a wide variety of biological processes. We demonstrate that the N6-adenosine methyltransferase METTL16 regulates expression of human MAT2A, which encodes the SAM synthetase expressed in most cells. Upon SAM depletion by methionine starvation, cells induce MAT2A expression by enhanced splicing of a retained intron. Induction requires METTL16 and its methylation substrate, a vertebrate conserved hairpin (hp1) in the MAT2A 3' UTR. Increasing METTL16 occupancy on the MAT2A 3' UTR is sufficient to induce efficient splicing. We propose that, under SAM-limiting conditions, METTL16 occupancy on hp1 increases due to inefficient enzymatic turnover, which promotes MAT2A splicing. We further show that METTL16 is the long-unknown methyltransferase for the U6 spliceosomal small nuclear RNA (snRNA). These observations suggest that the conserved U6 snRNA methyltransferase evolved an additional function in vertebrates to regulate SAM homeostasis.


Psychosocial services in rehabilitation medicine: an interdisciplinary approach.
Psychosocial adjustment to disability is an area of special need, often requiring intervention by mental health professionals, including social workers, psychologists, and psychiatrists. While the availability of all these disciplines is optimal for comprehensive psychosocial intervention, the use of multiple mental health disciplines may create problems of role confusion, overlapping efforts, and discontinuity of care. This paper presents the development of a psychosocial team as a method for identifying service goals, differentiating roles, coordinating psychosocial care, and educating rehabilitation staff on the expertise and proper use of the psychosocial disciplines. Four stages of team development are described: I. Identification of Purpose; II. Role Definition; III. Task Assignment; IV. Integration. A case example illustrates the functions of the interdisciplinary psychosocial team.


Alcohol use from adolescence through early adulthood: an assessment of measurement invariance by age and gender.
Studies on alcohol use and related constructs rarely test for measurement invariance to assess the reliability and validity of measures of alcohol use across different subpopulations of interest or ages. This failure to consider measurement invariance may result in biased parameter estimates and inferences. This study aimed to test measurement invariance of alcohol use across gender and age using a US nationally representative sample to inform future longitudinal studies assessing alcohol use. The National Longitudinal Study of Adolescent to Adult Health, a school-based, nationally representative longitudinal study conducted in 1994-95, 2001-02 and 2008. All regions within the United States; participants were selected via a clustered sample design from 80 high schools that represented the national population. Youth and young adults aged 13-31 years who had valid data on all three alcohol items within wave: 18 923 from wave 1; 14 315 from wave 3; and 14 785 from wave 4. Alcohol use measurement models were constructed using past-year general drinking frequency, heavy episodic drinking frequency and average quantity when drinking. Configural (factor structure), metric (factor loadings) and scalar (item intercepts) measurement invariance models were tested by gender and for each year of age from 13 to 31 years. All models passed the threshold for configural invariance. Comparisons between males and females demonstrated metric (and usually scalar) non-invariance for most ages beyond middle adolescence. Nearly all 1- and 2-year contrasts passed metric invariance. Scalar non-invariance was most prevalent in age comparisons between late adolescence and early adulthood, particularly for tests using 2-year age increments. Studies that do not account for the effects of gender and age on the measurement of alcohol use may be statistically biased.


Sickle hemoglobin confers tolerance to Plasmodium infection.
Sickle human hemoglobin (Hb) confers a survival advantage to individuals living in endemic areas of malaria, the disease caused by Plasmodium infection. As demonstrated hereby, mice expressing sickle Hb do not succumb to experimental cerebral malaria (ECM). This protective effect is exerted irrespectively of parasite load, revealing that sickle Hb confers host tolerance to Plasmodium infection. Sickle Hb induces the expression of heme oxygenase-1 (HO-1) in hematopoietic cells, via a mechanism involving the transcription factor NF-E2-related factor 2 (Nrf2). Carbon monoxide (CO), a byproduct of heme catabolism by HO-1, prevents further accumulation of circulating free heme after Plasmodium infection, suppressing the pathogenesis of ECM. Moreover, sickle Hb inhibits activation and/or expansion of pathogenic CD8(+) T cells recognizing antigens expressed by Plasmodium, an immunoregulatory effect that does not involve Nrf2 and/or HO-1. Our findings provide insight into molecular mechanisms via which sickle Hb confers host tolerance to severe forms of malaria.


Infection status outcome, machine learning method and virus type interact to affect the optimised prediction of hepatitis virus immunoassay results from routine pathology laboratory assays in unbalanced data.
Advanced data mining techniques such as decision trees have been successfully used to predict a variety of outcomes in complex medical environments. Furthermore, previous research has shown that combining the results of a set of individually trained trees into an ensemble-based classifier can improve overall classification accuracy. This paper investigates the effect of data pre-processing, the use of ensembles constructed by bagging, and a simple majority vote to combine classification predictions from routine pathology laboratory data, particularly to overcome a large imbalance of negative Hepatitis B virus (HBV) and Hepatitis C virus (HCV) cases versus HBV or HCV immunoassay positive cases. These methods were illustrated using a never before analysed data set from ACT Pathology (Canberra, Australia) relating to HBV and HCV patients. It was easier to predict immunoassay positive cases than negative cases of HBV or HCV. While applying an ensemble-based approach rather than a single classifier had a small positive effect on the accuracy rate, this also varied depending on the virus under analysis. Finally, scaling data before prediction also has a small positive effect on the accuracy rate for this dataset. A graphical analysis of the distribution of accuracy rates across ensembles supports these findings. Laboratories looking to include machine learning as part of their decision support processes need to be aware that the infection outcome, the machine learning method used and the virus type interact to affect the enhanced laboratory diagnosis of hepatitis virus infection, as determined by primary immunoassay data in concert with multiple routine pathology laboratory variables. This awareness will lead to the informed use of existing machine learning methods, thus improving the quality of laboratory diagnosis via informatics analyses.


The physiological significance of mitochondrial proton leak in animal cells and tissues.
Mitochondrial proton leak is an important component of cellular metabolism in animals and may account for as much as one quarter to one third of the Standard Metabolic Rate of the rat. The activity of the proton leak pathway is different in a wide range of animal species and in different thyroid states. Such differences imply some function for proton leak and candidates for this function include thermogenesis, protection against reactive oxygen species, endowment of metabolic sensitivity and maintenance of carbon fluxes.


Cancer registration literature update (2006-2008).
Using Cancer Registration and Registry as search items with PubMed, a survey of the relevant literature for the years 2006-2008 was performed. A total of 207 abstracts were scanned for core findings and classified under general incidence and mortality, methodology and specific organ headings, these accounting for 27%, 5% and 68% of papers, respectively. Further sub-division into geographical area and country showed 34% from Europe, less than 1% from Africa, 42% from Asia (almost half in the APJCP), 2% from Australasia and the remaining 21% from the Americas. Breast cancer was the most common specific cancer covered, followed by colorectal and childhood, then lung and urinary tract, but clear differences were noted in the focus of different countries, partially reflecting variation in prevalence. The distributions across and within continents point to geographical areas and countries in which assistance might allow a more comprehensive picture of cancer incidence and mortality to be generated, facilitating worldwide efforts for cancer control. Variation within countries also appears to require more emphasis in the future.


Comparison of electrochemical performances of olivine NaFePO4 in sodium-ion batteries and olivine LiFePO4 in lithium-ion batteries.
Carbon-coated olivine NaFePO(4) (C-NaFePO(4)) spherical particles with a uniform diameter of ∼80 nm are obtained by chemical delithiation and subsequent electrochemical sodiation of carbon-coated olivine LiFePO(4) (C-LiFePO(4)), which is synthesized by a solvothermal method. The C-NaFePO(4) electrodes are identical (particle size, particle size distribution, surface coating, and active material loading, etc.) to C-LiFePO(4) except that Li ions in C-LiFePO(4) are replaced by Na ions, making them ideal for comparison of thermodynamics and kinetics between C-NaFePO(4) cathode in sodium-ion (Na-ion) batteries and C-LiFePO(4) in lithium-ion (Li-ion) batteries. In this paper, the equilibrium potentials, reaction resistances, and diffusion coefficient of Na in C-NaFePO(4) are systematically investigated by using the galvanostatic intermittent titration technique (GITT), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), and compared to those of the well-known LiFePO(4) cathodes in Li-ion batteries. Due to the lower diffusion coefficient of Na-ion and higher contact and charge transfer resistances in NaFePO(4) cathodes, the rate performance of C-NaFePO(4) in Na-ion batteries is much worse than that of C-LiFePO(4) in Li-ion batteries. However, the cycling stability of C-NaFePO(4) is almost comparable to C-LiFePO(4) by retaining 90% of its capacity even after 100 charge-discharge cycles at a charge-discharge rate of 0.1 C.


Fibrillar beta-amyloid impairs the late phase of long term potentiation.
Synaptic dysfunction is involved in early stages of Alzheimer's disease (AD). Amyloid-beta peptides (Abeta), a neuropathologic hallmark of the disease, have been shown to alter synaptic function. Given that Abeta is present in different forms including monomeric, oligomeric and fibrillar species, we have investigated whether fibrillar Abeta impairs synaptic function. Here we report that a synthetic fibrillar form of Abeta impairs the late protein-synthesis dependent phase of LTP without affecting the early protein-synthesis independent phase. These findings add to previous reports that Abeta oligomers are highly toxic to cells and might cause synaptic dysfunction, and suggest that a therapeutic intervention in AD should include the use of drugs inhibiting and disassembling fibril formation in addition to drugs inhibiting oligomers formation.


Size and density characterization of human committed and multipotent hematopoietic progenitors.
Physical characterization of human blood and bone marrow (BM) hematopoietic precursors is necessary for the design of adequate techniques to isolate these cells for experimental and possible clinical use. Elutriation and continuous Percoll gradient were used to define the size and density of committed (CFU-GM, BFU-E, and CFU-E) and multipotent (CFU-MIX) progenitors on paired BM and blood samples from normal donors. Cells were initially prepared over Ficoll-Hypaque (specific gravity 1.077 g/cm3). Elutriation was performed on a Beckman JE-6B rotor with a standard chamber at 2000 rpm using flow rates of 7-23 ml/min. Percoll gradients were centered at 1.070 g/cm3 using ultracentrifugation. Cell density was determined using marker beads. Density was slightly higher for BM than for blood progenitors of the same class. Progenitor sizes (proportionate to elutriation flow rate) were similar in BM and blood. CFU-MIX, BFU-E, and CFU-GM coseparated in blood and BM; CFU-E (BM) were larger and more dense than other BM progenitors. BM and blood E-rosette-positive cells were separated more effectively by size than by density. The similarity in size and small differences in density between blood and BM progenitors may allow adaption of blood separation techniques (apheresis) to processing of BM for cryopreservation and/or in vitro treatment. Similarly, the ability to separate T cells from progenitors in blood by elutriation (albeit only partially), as has been described for BM, may help in the modification of existing apheresis techniques to achieve such separations.


Functional interaction between InsP3 receptors and store-operated Htrp3 channels.
Calcium ions are released from intracellular stores in response to agonist-stimulated production of inositol 1,4,5-trisphosphate (InsP3), a second messenger generated at the cell membrane. Depletion of Ca2+ from internal stores triggers a capacitative influx of extracellular Ca2+ across the plasma membrane. The influx of Ca2+ can be recorded as store-operated channels (SOC) in the plasma membrane or as a current known as the Ca2+-release-activated current (I(crac)). A critical question in cell signalling is how SOC and I(crac) sense and respond to Ca2+-store depletion: in one model, a messenger molecule is generated that activates Ca2+ entry in response to store depletion; in an alternative model, InsP3 receptors in the stores are coupled to SOC and I(crac). The mammalian Htrp3 protein forms a well defined store-operated channel and so provides a suitable system for studying the effect of Ca2+-store depletion on SOC and I(crac). We show here that Htrp3 channels stably expressed in HEK293 cells are in a tight functional interaction with the InsP3 receptors. Htrp3 channels present in the same plasma membrane patch can be activated by Ca2+ mobilization in intact cells and by InsP3 in excised patches. This activation of Htrp3 by InsP3 is lost on extensive washing of excised patches but is restored by addition of native or recombinant InsP3-bound InsP3 receptors. Our results provide evidence for the coupling hypothesis, in which InsP3 receptors activated by InsP3 interact with SOC and regulate I(crac).


Migratory birds and spread of West Nile virus in the Western Hemisphere.
West Nile virus, an Old World flavivirus related to St. Louis encephalitis virus, was first recorded in the New World during August 1999 in the borough of Queens, New York City. Through October 1999, 62 patients, 7 of whom died, had confirmed infections with the virus. Ornithophilic mosquitoes are the principal vectors of West Nile virus in the Old World, and birds of several species, chiefly migrants, appear to be the major introductory or amplifying hosts. If transovarial transmission or survival in overwintering mosquitoes were the principal means for its persistence, West Nile virus might not become established in the New World because of aggressive mosquito suppression campaigns conducted in the New York area. However, the pattern of outbreaks in southern Europe suggests that viremic migratory birds may also contribute to movement of the virus. If so, West Nile virus has the potential to cause outbreaks throughout both temperate and tropical regions of the Western Hemisphere.


Prenatal diagnosis of MPPH syndrome.
We report the prenatal sonographic detection of a fetus with megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephaly. Only 14 patients have been reported in the literature so far, all but one were diagnosed postnatally. The polymicrogyria in the frontoparietal lobe was confirmed by prenatal magnetic resonance imaging. Additionally, a hypoplastic thymus as seen in a 22q11 deletion was present. Although polymicrogyria along with pre-axial polydactyly has been described in 22q11 deletion, the diagnosis of Di George syndrome was ruled out. The etiology of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephaly has not been revealed yet. A dominant as well as recessive inheritance has been suggested.


University of Wisconsin solution versus Celsior solution in clinical pancreas transplantation.
This study compared the safety and efficacy of University of Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation (PTx). A retrospective review of 154 PTx performed over a 61-month period included 77 grafts preserved with UW and 77 with C. The two groups were comparable for both donor and recipient characteristics. After a mean cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672 minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow-up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P = NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04). Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW compared with 90.4% and 90.4% for C (P = NS). Within the range of cold ischemia times reported in this study, UW and C show similar safety and efficacy profiles for PTx.


A comparison between tracer gas and aerosol particles distribution indoors: The impact of ventilation rate, interaction of airflows, and presence of objects.
The study investigated the separate and combined effects of ventilation rate, free convection flow produced by a thermal manikin, and the presence of objects on the distribution of tracer gas and particles in indoor air. The concentration of aerosol particles and tracer gas was measured in a test room with mixing ventilation. Three layouts were arranged: an empty room, an office room with an occupant sitting in front of a table, and a single-bed hospital room. The room occupant was simulated by a thermal manikin. Monodisperse particles of three sizes (0.07, 0.7, and 3.5 μm) and nitrous oxide tracer gas were generated simultaneously at the same location in the room. The particles and gas concentrations were measured in the bulk room air, in the breathing zone of the manikin, and in the exhaust air. Within the breathing zone of the sitting occupant, the tracer gas emerged as reliable predictor for the exposure to all different-sized test particles. A change in the ventilation rate did not affect the difference in concentration distribution between tracer gas and larger particle sizes. Increasing the room surface area did not influence the similarity in the dispersion of the aerosol particles and the tracer gas.


CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment.
The cytoplasmic linker protein (CLIP)-170, an outer kinetochore protein, has a role in kinetochore-microtubule attachment and chromosome alignment during mitosis. However, the mechanism by which CLIP-170 is involved in chromosome alignment is not known. Here, we show that CLIP-170 colocalizes with Polo-like kinase 1 (PLK1) at kinetochores during early mitosis. Depletion of CLIP-170 results in a significant reduction in PLK1 recruitment to kinetochores and causes kinetochore-fiber (K-fiber) instability and defects in chromosome alignment at the metaphase plate. These phenotypes are dependent on the phosphorylation of CLIP-170 at a CDK1-dependent site, T287, as ectopic expression of wild-type CLIP-170, but not the expression of a non-phosphorylatable mutant, CLIP-170-T287A, restores PLK1 localization at kinetochores and rescues K-fiber stability and chromosome alignment in CLIP-170-depleted cells. These data suggest that CLIP-170 acts as a novel recruiter and spatial regulator of PLK1 at kinetochores during early mitosis, promoting K-fiber stability and chromosome alignment for error-free chromosome segregation.


Does enteral protein intake affect renal glomerular and tubular functions in very low birth weight infants?
Very low birth weight infants require 3 - 4 g/kg/day protein intake to provide satisfactory postnata growth rates and neurodevelopmental outcomes. However, they have fewer functional nephrons, thereby increasing vulnerability for impaired renal functions. The aim of this study was to investigate the effect of different amounts of enteral protein intake during the fortification of human milk on renal glomerular and tubular functions. Preterm infants were randomized into three groups in terms of their daily protein intake: standard fortification (3 g/kg/d), moderate fortification (3.3 g/kg/d), and aggressive fortification (3.6 g/kg/d). Serum urea, creatinine (Cr), Cystatin C (Cys-C) and urinary β2 microglobulin (β2M) levels were assessed and compared between groups. Serum urea, Cr, Cys-C and urinary β2M levels were similar in all three groups, both on discharge and postnatal Day 14 (p > 0.05). Mean Cr and β2M levels were significantly lower on discharge (p < 0.05), while Cys-C levels did not differ in time (p > 0.05). Enteral protein intake up to 3.6 g/kg/d did not alter the tubular and glomerular functions in very preterm infants. However, the long-term renal effects in these infants maintained on a high protein intake remain unknown and should be addressed in future studies.


The Vascular Study Group of New England Cardiac Risk Index (VSG-CRI) predicts cardiac complications more accurately than the Revised Cardiac Risk Index in vascular surgery patients.
The Revised Cardiac Risk Index (RCRI) is a widely used model for predicting cardiac events after noncardiac surgery. We compared the accuracy of the RCRI with a new, vascular surgery-specific model developed from patients within the Vascular Study Group of New England (VSGNE). We studied 10,081 patients who underwent nonemergent carotid endarterectomy (CEA; n = 5293), lower extremity bypass (LEB; n = 2673), endovascular abdominal aortic aneurysm repair (EVAR; n = 1005), and open infrarenal abdominal aortic aneurysm repair (OAAA; n = 1,110) within the VSGNE from 2003 to 2008. First, we analyzed the ability of the RCRI to predict in-hospital major adverse cardiac events, including myocardial infarction (MI), arrhythmia, or congestive heart failure (CHF) in the VSGNE cohort. Second, we used a derivation cohort of 8208 to develop a new cardiac risk prediction model specifically for vascular surgery patients. Chi-square analysis identified univariate predictors, and multivariate logistic regression was used to develop an aggregate and four procedure-specific risk prediction models for cardiac complications. Calibration and model discrimination were assessed using Pearson correlation coefficient and receiver operating characteristic (ROC) curves. The ability of the model to predict cardiac complications was assessed within a validation cohort of 1873. Significant predictors were converted to an integer score to create a practical cardiac risk prediction formula. The overall incidence of major cardiac events in the VSGNE cohort was 6.3% (2.5% MI, 3.9% arrhythmia, 1.8% CHF). The RCRI predicted risk after CEA reasonably well but substantially underestimated risk after LEB, EVAR, and OAAA for low- and higher-risk patients. Across all VSGNE patients, the RCRI underestimated cardiac complications by 1.7- to 7.4-fold based on actual event rates of 2.6%, 6.7%, 11.6%, and 18.4% for patients with 0, 1, 2, and >or=3 risk factors. In multivariate analysis of the VSGNE cohort, independent predictors of adverse cardiac events were (odds ratio [OR]) increasing age (1.7-2.8), smoking (1.3), insulin-dependent diabetes (1.4), coronary artery disease (1.4), CHF (1.9), abnormal cardiac stress test (1.2), long-term beta-blocker therapy (1.4), chronic obstructive pulmonary disease (1.6), and creatinine >or=1.8 mg/dL (1.7). Prior cardiac revascularization was protective (OR, 0.8). Our aggregate model was well calibrated (r = 0.99, P < .001), demonstrating moderate discriminative ability (ROC curve = 0.71), which differed only slightly from the procedure-specific models (ROC curves: CEA, 0.74; LEB, 0.72; EVAR, 0.74; OAAA, 0.68). Rates of cardiac complications for patients with 0 to 3, 4, 5, and >or=6 VSG risk factors were 3.1%, 5.0%, 6.8%, and 11.6% in the derivation cohort and 3.8%, 5.2%, 8.1%, and 10.1% in the validation cohort. The VSGNE cardiac risk model more accurately predicted the actual risk of cardiac complications across the four procedures for low- and higher-risk patients than the RCRI. When the VSG Cardiac Risk Index (VSG-CRI) was used to score patients, six categories of risk ranging from 2.6% to 14.3% (score of 0-3 to 8) were discernible. The RCRI substantially underestimates in-hospital cardiac events in patients undergoing elective or urgent vascular surgery, especially after LEB, EVAR, and OAAA. The VSG-CRI more accurately predicts in-hospital cardiac events after vascular surgery and represents an important tool for clinical decision making.


[Treatment of primary liver tumors].
The paper is concerned with the analysis of the results of surgical and drug therapy of 225 cases of primary hepatic tumor treated at the Center clinic within 1957-1981. 86 patients were operated on: radical surgery was performed in 20 cases. Postoperative lethality rate in radical surgery group was 10%, mean survival time-26.7 months. Systemic chemotherapy was given to 111, and regional one-to 12 patients. New schemes of drug treatment (carminomycin + bleomycin; preparations of platinum + other cytostatic drugs) were used in 30 cases. This was followed by a higher effectiveness of treatment and a longer survival, the latter being 9.0 +/- 1.3 months, as compared with 4.0 +/- 0.5 months in controls.