Assessment of Demineralization Inhibition Effects of Dentin Desensitizers Using Swept-Source Optical Coherence Tomography.
The purpose of this study was to evaluate the mechanism of action and the inhibiting effects of two types of desensitizers against dentin demineralization using pre-demineralized hypersensitivity tooth model in vitro. In this study, we confirmed that a hypersensitivity tooth model from our preliminary experiment could be prepared by immersing dentin discs in an acetic acid-based solution with pH 5.0 for three days. Dentin discs with three days of demineralization were prepared and applied by one of the desensitizers containing calcium fluoro-alumino-silicate glass (Nanoseal, NS) or fluoro-zinc-silicate glass (Caredyne Shield, CS), followed by an additional three days of demineralization. Dentin discs for three days of demineralization (de3) and six days of demineralization (de6) without the desensitizers were also prepared. The dentin discs after the experimental protocol were scanned using swept-source optical coherence tomography (SS-OCT) to image the cross-sectional (2D) view of the samples and evaluate the SS-OCT signal. The signal intensity profiles of SS-OCT from the region of interest of 300, 500, and 700 µm in depth were obtained to calculate the integrated signal intensity and signal attenuation coefficient. The morphological differences and remaining chemical elements of the dentin discs were also analyzed using scanning electron microscopy and energy-dispersive X-ray spectroscopy. SS-OCT images of CS and NS groups showed no obvious differences between the groups. However, SS-OCT signal profiles for both the CS and NS groups showed smaller attenuation coefficients and larger integrated signal intensities than those of the de6 group. Reactional deposits of the desensitizers even after the additional three days of demineralization were observed on the dentin surface in NS group, whereas remnants containing Zn were detected within the dentinal tubules in CS group. Consequently, both CS and NS groups showed inhibition effects against the additional three days of demineralization in this study. Our findings demonstrate that SS-OCT signal analysis can be used to monitor the dentin demineralization and inhibition effects of desensitizers against dentin demineralization in vitro.


The "booty call": a compromise between men's and women's ideal mating strategies.
Traditionally, research on romantic and sexual relationships has focused on one-night stands and monogamous pairs. However, as the result of men and women pursuing their ideal relationship types, various compromise relationships may emerge. One such compromise is explored here: the "booty call." The results of an act-nomination and frequency study of college students provided an initial definition and exploration of this type of relationship. Booty calls tend to utilize various communication mediums to facilitate sexual contact among friends who, for men, may represent low-investment, attractive sexual partners and, for women, may represent attractive test-mates. The relationship is discussed as a compromise between men's and women's ideal mating strategies that allows men greater sexual access and women an ongoing opportunity to evaluate potential long-term mates.


Insular thyroid carcinoma in adolescents: a potentially lethal endocrine malignancy.
Insular thyroid carcinoma is intermediate in aggressiveness between well differentiated and anaplastic thyroid carcinomas. The authors describe two children with insular thyroid carcinoma who had markedly different outcomes. In the first case, a girl age 15 years, 2 months presented with a large pulsatile mass in the right thyroid lobe. In the second case, a girl age 16 years, 3 months presented after total thyroidectomy was performed elsewhere for confirmed pTNM Stage I insular thyroid carcinoma. In Case 1, total thyroidectomy was performed, and histologic examination revealed insular thyroid carcinoma with lymph node involvement. Six weeks postoperatively, neck masses reappeared. There was significant radioactive iodine uptake in the thyroid bed and in a palpable right supraclavicular lymph node; this was associated with an increased serum thyroglobulin level. Ultrasound-guided biopsy of the lymph node confirmed recurrent insular carcinoma, and neck dissection was performed. Six weeks later, there was 0.35% iodine uptake in the neck, and the patient was treated with 300 mCi of (131)I. She had no signs of recurrence when last seen 22 months postoperatively. In Case 2, the patient was given 29.9 mCi of (131)I for remnant ablation. Four months postoperatively, fine-needle aspiration biopsy of a high jugular lymph node demonstrated recurrence. The patient was given 200 mCi of (131)I but had no significant response. Right modified neck dissection was performed, followed by external beam radiation. Despite aggressive treatment with a further 500 mCi of (131)I, progressive lung and mediastinal metastases developed, followed by brain metastasis. The patient died 31 months after the initial diagnosis. Insular thyroid carcinoma may occur and behave aggressively in children. Vigorous initial surgical and radioactive iodine treatments are warranted.


Economic impact of adult obesity on health systems: a systematic review.
Obesity represents an important public health issue. An assessment of its costs would be useful to provide recommendations for policy and decision-making strategies. The aims of our study were to carry out a systematic review to assess the economic burden of adult obesity in terms of direct and indirect costs and to perform a quality appraisal of the analysed studies. A literature search was carried out on PubMed, Scopus and Cochrane Library to retrieve cost-of-illness (COI) analyses focused on adult (aged 18 years or more) overweight or obese people and published up to 2013. COI analyses that considered direct and indirect costs were included. Each included manuscript was independently appraised by three groups of researchers on the basis of the British Medical Journal Drummond's checklist. Approximately 2044 articles were initially retrieved, and 17 were included in the current review. The included studies showed a medium-high-quality level. The available studies seemed to be heterogeneous both in terms of methodology and results reporting. However, as many studies have been conducted from the payer perspective, just direct medical costs can be considered exhaustive. As only three studies included considered also indirect costs, there is no strong evidence to give a comprehensive picture of this phenomenon also from the societal perspective. The review confirmed that obesity absorbs a huge amount of health-care resources. Further research is therefore needed to better understand the economic impact and to identify and promote public health strategies to tackle obesity.


Access to information and decision making on teenage pregnancy prevention by females in Tshwane.
The increase in the number of teenage pregnancies and its negative consequences has encouraged various researchers to explore the possible causes of teenage pregnancy. Findings from previously-conducted research have indicated different preventable factors that predispose female teenagers to pregnancy, such as staff attitudes and the lack of information resulting from poor access to health facilities. To explore and describe access to information and decision making on teenage pregnancy prevention by females using a primary healthcare clinic in Tshwane, South Africa. In this study, the researchers used a descriptive qualitative and exploratory research design to explore and describe the verbal reports regarding prevention of teenage pregnancy by females using a primary healthcare clinic in Tshwane, South Africa. Face-to-face semistructured interviews were conducted with 15 female participants aged between 15 and 26, who had been pregnant once or more during their teens. Two themes emerged, namely, access to information and decision making by female teenagers. Five categories that emerged were: access to information on pregnancy prevention; ignoring of provided information; the use of alternative medicine with hormonal contraception; personal reasons for use and non-use of contraception; and decisions made by teenagers to not fall pregnant. Females in this study fell pregnant in their teens, even though they had access to information. Given the complexity of this problem, female teenagers should use their families as primary sources of information for reproductive health promotion and educational institutions should build on this to aid the prevention of teenage pregnancy.


Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase.
Eukaryotic cells can synthesize the non-essential amino acid arginine from aspartate and citrulline using the enzyme argininosuccinate synthetase (ASS). It has been observed that ASS is underexpressed in various types of cancers ASS, for which arginine become auxotrophic. Arginine deiminase (ADI) is a prokaryotic enzyme that metabolizes arginine to citrulline and has been found to inhibit melanoma and hepatoma cancer cells deficient of ASS. We tested the hypothesis that pancreatic cancers have low ASS expression and therefore arginine deprivation by ADI will inhibit cell growth. ASS expression was examined in 47 malignant and 20 non-neoplastic pancreatic tissues as well as a panel of human pancreatic cancer cell lines. Arginine deprivation was achieved by treatment with a recombinant form of ADI formulated with polyethylene glycol (PEG-ADI). Effects on caspase activation, cell growth and cell death were examined. Furthermore, the effect of PEG-ADI on the in vivo growth of pancreatic xenografts was examined. Eighty-seven percent of the tumors lacked ASS expression; 5 of 7 cell lines similarly lacked ASS expression. PEG-ADI specifically inhibited growth of those cell lines lacking ASS. PEG-ADI treatment induced caspase activation and induction of apoptosis. PEG-ADI was well tolerated in mice despite complete elimination of plasma arginine; tumor growth was inhibited by approximately 50%. Reduced expression of ASS occurs in pancreatic cancer and predicts sensitivity to arginine deprivation achieved by PEG-ADI treatment. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of pancreatic cancer, a malignancy in which new therapy is desperately needed.


Synthesis of Stable Cholesteryl-Polyethylene Glycol-Peptide Conjugates with Non-Disperse Polyethylene Glycol Lengths.
A method for conjugating cholesterol to peptide ligands through non-disperse polyethylene glycol (ND-PEG) through a non-hydrolysable linkage is described. The iterative addition of tetraethylene glycol macrocyclic sulfate to cholesterol (Chol) renders a family of highly pure well-defined Chol-PEG compounds with different PEG lengths from 4 up to 20 ethylene oxide units, stably linked through an ether bond. The conjugation of these Chol-PEG compounds to the cyclic (RGDfK) peptide though Lys5 side chains generates different lengths of Chol-PEG-RGD conjugates that retain the oligomer purity of the precursors, as analysis by HRMS and NMR has shown. Other derivatives were synthesized with similar results, such as Chol-PEG-OCH3 and Chol-PEG conjugated to glutathione and Tf1 peptides through maleimide-thiol chemoselective ligation. This method allows the systematic synthesis of highly pure uniform stable Chol-PEGs, circumventing the use of activation groups on each elongation step and thus reducing the number of synthesis steps.


The relationship between neighborhood poverty and alcohol use: estimation by marginal structural models.
Previous studies on the relationship of neighborhood disadvantage with alcohol use or misuse have often controlled for individual characteristics on the causal pathway, such as income-thus potentially underestimating the relationship between disadvantage and alcohol consumption. We used data from the Coronary Artery Risk Development in Young Adults study of 5115 adults aged 18-30 years at baseline and interviewed 7 times between 1985 and 2006. We estimated marginal structural models using inverse probability-of-treatment and censoring weights to assess the association between point-in-time/cumulative exposure to neighborhood poverty (proportion of census tract residents living in poverty) and alcohol use/binging, after accounting for time-dependent confounders including income, education, and occupation. The log-normal model was used to estimate treatment weights while accounting for highly-skewed continuous neighborhood poverty data. In the weighted model, a one-unit increase in neighborhood poverty at the prior examination was associated with a 86% increase in the odds of binging (OR = 1.86 [95% confidence interval = 1.14-3.03]); the estimate from a standard generalized-estimating-equations model controlling for baseline and time-varying covariates was 1.47 (0.96-2.25). The inverse probability-of-treatment and censoring weighted estimate of the relative increase in the number of weekly drinks in the past year associated with cumulative neighborhood poverty was 1.53 (1.02-2.27); the estimate from a standard model was 1.16 (0.83-1.62). Cumulative and point-in-time measures of neighborhood poverty are important predictors of alcohol consumption. Estimators that more closely approximate a causal effect of neighborhood poverty on alcohol provided a stronger estimate than estimators from traditional regression models.


Evolving use of seizure medications after intracerebral hemorrhage: A multicenter study.
Prophylactic medications can be a source of preventable harm, potentially affecting large numbers of patients. Few data exist about how clinicians change prescribing practices in response to new data and revisions to guidelines about preventable harm from a prophylactic medication. We sought to determine the changes in prescribing practice of seizure medications for patients with intracerebral hemorrhage (ICH) across a metropolitan area before and after new outcomes data and revised prescribing guidelines were published. We conducted an observational study using electronic medical record data from 4 academic medical centers in a large US metropolitan area. A total of 3,422 patients with ICH, diagnosed between 2007 and 2012, were included. In 2009, after a publication found an association of phenytoin with higher odds of dependence or death, the use of phenytoin declined from 9.6% in 2009 to 2.2% in 2012 (p < 0.00001). Conversely, the use of levetiracetam more than doubled, from 15.1% in 2007 to 35% in 2012 (p < 0.00001). Use of levetiracetam varied among the 4 institutions from 6.7% to 29.8% (p < 0.00001). New data that led to revised prescribing guidelines for prophylactic seizure medications for patients with ICH were temporally associated with a significant decrease in use of the medication, potentially reducing adverse outcomes. However, a corresponding increase in the use of an alternative medication, levetiracetam, occurred despite limited knowledge about its potential effects on outcomes. Future guideline changes should anticipate and address alternatives.


Extraintestinal Manifestations of Inflammatory Bowel Disease.
Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD.


How Metabolic Diseases Impact the Use of Antimicrobials: A Formal Demonstration in the Field of Veterinary Medicine.
Decreasing the use of antimicrobials has become a primary objective for both human and veterinary medicine in many countries. Medical prevention and good nutrition are seen as key parameters for reducing antimicrobial use. However, little consideration has been given to how metabolic diseases may influence the use of antimicrobials in humans and animals through limiting the prevalence and severity of infectious diseases. To quantify this relationship using the example of a common metabolic disease in dairy cows (subclinical ketosis, SCK), we constructed a stochastic model reporting the total quantity of curative antimicrobials for a given population with the prevalence of cows at risk for SCK. We considered the prevalence of SCK, the relative risk of the disease in cases of SCK compared to no SCK and the use of antimicrobials to treat SCK-induced infectious diseases. Reducing the percentage of cows at risk for SCK from 80% to 10% was associated with an average decrease in the use of antimicrobials of 11% (prevalence of SCK from 34% to 17%, respectively) or 25% (prevalence of SCK from 68% to 22%, respectively), depending on the relative risk to contract SCK if risk was present. For a large percentage of the cows at risk for SCK, using a preventive bolus of monensin reduced the use of curative antimicrobials to the same level that was observed when the percentage of cows at risk for SCK was low. The present work suggests similar approaches for obesity and diabetes.


Launching of the Anaemia Research Peruvian Cohort (ARPEC): a multicentre birth cohort project to explore the iron adaptive homeostasis, infant growth and development in three Peruvian regions.
Preventing infantile anaemia and ensuring optimal growth and development during early childhood, particularly in resource-constrained settings, represent an ongoing public health challenge. Current responses are aligned to treatment-based solutions, instead of determining the roles of its inter-related causes. This project aims to assess and understand the complex interplay of eco-bio-social-political factors that determine infantile anaemia to inform policy, research design and prevention practices. This is a longitudinal birth cohort study including four components: (1) biological, will assess known blood markers of iron homeostasis and anaemia and stool microbiota to identify and genetically analyse the participants' flora; (2) ecological, will assess and map pollutants in air, water and soil and evaluate features of nutrition and perceived food security; (3) social, which will use different qualitative research methodologies to explore key stakeholders and informants' perceptions related to nutritional, environmental and anaemia topics, participant observations and a participatory approach and (4) a political analysis, to identify and assess the impact of policies, guidelines and programmes at all levels for infantile anaemia in the three regions. Finally, we will also explore the role of social determinants and demographic variables longitudinally for all study participants. This project aims to contribute to the evidence of the inter-related causal factors of infantile anaemia, addressing the complexity of influencing factors from diverse methodological angles. We will assess infantile anaemia in three regions of Peru, including newborns and their mothers as participants, from childbirth until their first year of age. Ethical approval was obtained from the Institutional Research Ethics Committee of the Instituto Nacional de Salud del Niño (Lima, Peru), CIEI-043-2019. An additional opinion has been granted by the Ethical Committee of Queen Mary University of London (London, UK). Dissemination across stakeholders is taking part as a continues part of the research process.


Influence of the helical and six available Cardan sequences on 3D ankle joint kinematic parameters.
Cardan/Euler and helical angles are the popular methods of quantifying angular kinematics. Cardan angles are sequence dependent and crosstalk can influence the kinematic calculations. The International Society of Biomechanics (ISB) recommends a sagittal, coronal, and then transverse (XYZ) sequence of rotations, although it has been proposed that when calculating rotations outside of the sagittal plane, this may not be the most appropriate method. This study investigated the influence of the helical and six available Cardan sequences on three-dimensional (3D) ankle joint kinematics. Kinematic data were obtained using an eight-camera motion analysis system as participants ran at 4.0 m/s +/- 5%. Repeated measures ANOVAs were used to compare kinematic parameters, and intraclass correlations were employed to identify evidence of crosstalk across planes. The results indicate that in the transverse and coronal planes, peak angle and range of motion values using the YXZ and ZXY sequences were significantly greater than the other sequences. Furthermore, utilization of YXZ and ZXY sequences was associated with the strongest correlations from the sagittal plane, and the XYZ sequence was found to be associated with the lowest correlations. It appears that for the representation of 3D ankle joint kinematics, the XYZ sequence is associated with minimal planar crosstalk and as such its use is encouraged.


1053-nm-wavelength selection in a diode-laser-pumped Nd:YLF laser.
We report on a Nd:YLF laser that operates at 1053 nm without optical intracavity elements for the suppression of the stronger 1047-nm transition. The Nd:YLF crystal is end pumped by a fiber optically coupled 10-W diode-laser bar. The different thermal-lensing focal lengths of the two main lasing wavelengths in a plane-parallel resonator were used to achieve the selection by tilting the end mirror slightly from its optimum position for maximum output power. With 9.8-W cw diode-laser-pumping power the 1053-nm Nd:YLF laser produces a maximum output power of 1.9 W in cw operation and nearly 1 W of average power at a Q-switch repetition rate of 15 kHz. The highest slope efficiency of 47% achieved in cw operation.


Comparative genomics of hemiascomycete yeasts: genes involved in DNA replication, repair, and recombination.
Among genes conserved from bacteria to mammals are those involved in replicating and repairing DNA. Following the complete sequencing of four hemiascomycetous yeast species during the course of the Genolevures 2 project, we have studied the conservation of 106 genes involved in replication, repair, and recombination in Candida glabrata, Kluyveromyces lactis, Debaryomyces hansenii, and Yarrowia lipolytica and compared them with their Saccharomyces cerevisiae orthologues. We found that proteins belonging to the replication fork and to the nucleotide excision repair pathway were-on the average-more conserved than proteins involved in the checkpoint response to DNA damage or in meiotic recombination. The meiotic recombination proteins Spo11p and Mre11p-Rad50p, involved in making meiotic double-strand breaks (DSBs), are conserved as is Mus81p, involved in resolving meiotic recombination intermediates. Interestingly, genes found in organisms in which DSB-repair is required for proper synapsis during meiosis are also found in C. glabrata, K. lactis, and D. hansenii but not in Y. lipolytica, suggesting that two modes of meiotic recombination have been selected during evolution of the hemiascomycetous yeasts. In addition, we found that SGS1 and TOP1, respectively, a DEAD/DEAH helicase and a type I topoisomerase, are duplicated in C. glabrata and that SRS2, a helicase involved in homologous recombination, is tandemly duplicated in K. lactis. Phylogenetic analyses show that the duplicated SGS1 gene evolved faster than the original gene, probably leading to a specialization of function of the duplicated copy.


Coupling between skeletal muscle fiber size and capillarization is maintained during healthy aging.
As muscle capillarization is related to the oxidative capacity of the muscle and the size of muscle fibres, capillary rarefaction may contribute to sarcopenia and functional impairment in older adults. Therefore, it is important to assess how ageing affects muscle capillarization and the interrelationship between fibre capillary supply with the oxidative capacity and size of the fibres. Muscle biopsies from healthy recreationally active young (22 years; 14 men and 5 women) and older (74 years; 22 men and 6 women) people were assessed for muscle capillarization and the distribution of capillaries with the method of capillary domains. Oxidative capacity of muscle fibres was assessed with quantitative histochemistry for succinate dehydrogenase (SDH) activity. There was no significant age-related reduction in muscle fibre oxidative capacity. Despite 18% type II fibre atrophy (P = 0.019) and 23% fewer capillaries per fibre (P < 0.002) in the old people, there was no significant difference in capillary distribution between young and old people, irrespective of sex. The capillary supply to a fibre was primarily determined by fibre size and only to a small extent by oxidative capacity, irrespective of age and sex. Based on SDH, the maximal oxygen consumption supported by a capillary did not differ significantly between young and old people. The similar quantitative and qualitative distribution of capillaries within muscle from healthy recreationally active older people and young adults indicates that the age-related capillary rarefaction, which does occur, nevertheless maintains the coupling between skeletal muscle fibre size and capillarization during healthy ageing.


Phase grating design for a dual-band snapshot imaging spectrometer.
Infrared spectral features have proved useful in the identification of threat objects. Dual-band focal-plane arrays (FPAs) have been developed in which each pixel consists of superimposed midwave and long-wave photodetectors [Dyer and Tidrow, Conference on Infrared Detectors and Focal Plane Arrays (SPIE, Bellingham, Wash., 1999), pp. 434-440]. Combining dual-band FPAs with imaging spectrometers capable of interband hyperspectral resolution greatly improves spatial target discrimination. The computed-tomography imaging spectrometer (CTIS) [Descour and Dereniak, Appl. Opt. 34, 4817-4826 (1995)] has proved effective in producing hyperspectral images in a single spectral region. Coupling the CTIS with a dual-band detector can produce two hyperspectral data cubes simultaneously. We describe the design of two-dimensional, surface-relief, computer-generated hologram dispersers that permit image information in these two bands simultaneously.


RhinAsthma patient perspective: A Rasch validation study.
In daily practice, Health-Related Quality of Life (HRQoL) tools are useful for supplementing clinical data with the patient's perspective. To encourage their use by clinicians, the availability of tools that can quickly provide valid results is crucial. A new HRQoL tool has been proposed for patients with asthma and rhinitis: the RhinAsthma Patient Perspective-RAPP. The aim of this study was to evaluate the psychometric robustness of the RAPP using the Item Response Theory (IRT) approach, to evaluate the scalability of items and test whether or not patients use the items response scale correctly. 155 patients (53.5% women, mean age 39.1, range 16-76) were recruited during a multicenter study. RAPP metric properties were investigated using IRT models. Differential item functioning (DIF) was used for gender, age, and asthma control test (ACT). The RAPP adequately fitted the Rating Scale model, demonstrating the equality of the rating scale structure for all items. All statistics on items were satisfactory. The RAPP had adequate internal reliability and showed good ability to discriminate among different groups of participants. DIF analysis indicated that there were no differential item functioning issues for gender. One item showed a DIF by age and four items by ACT. The psychometric evaluation performed using IRT models demonstrated that the RAPP met all the criteria to be considered a reliable and valid method of measurement. From a clinical perspective, this will allow physicians to confidently interpret scores as good indicators of Quality of Life of patients with asthma.


Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting.
Substantial improvements in survival have been seen in multiple myeloma (MM) over recent years, associated with the introduction and widespread use of multiple novel agents and regimens, as well as the emerging treatment paradigm of continuous or long-term therapy. However, these therapies and approaches may have limitations in the community setting, associated with toxicity burden, patient burden, and other factors including cost. Consequently, despite improvements in efficacy in the rigorously controlled clinical trials setting, the same results are not always achieved in real-world practice. Furthermore, the large number of different treatment options and regimens under investigation in various MM settings precludes the feasibility of obtaining head-to-head clinical trial data, and there is a temptation to use cross-trial comparisons to evaluate data across regimens. However, multiple aspects, including patient-related, disease-related, and treatment-related factors, can influence clinical trial outcomes and lead to differences between studies that may confound direct comparisons between data. In this review, we explore the various factors requiring attention when evaluating clinical trial data across available agents/regimens, as well as other considerations that may impact the translation of these findings into everyday MM management. We also investigate discrepancies between clinical trial efficacy and real-world effectiveness through a literature review of non-clinical trial data in relapsed/refractory MM on novel agent-based regimens and evaluate these data in the context of phase 3 trial results for recently approved and commonly used regimens. We thereby demonstrate the complexity of interpreting data across clinical studies in MM, as well as between clinical studies and routine-care analyses, with the aim to help clinicians consider all the necessary issues when tailoring individual patients' treatment approaches.


Prevalence of work-related musculoskeletal symptoms of the neck and upper extremity among dentists in China.
Studies from western countries show that dentists are vulnerable to work-related musculoskeletal disorders (WMSDs) of the neck and upper extremities, but little is known about their epidemiology among members of this rapidly growing profession in China. This study aims to investigate the prevalence of WMSDs and identify potential risk factors associated with their occurrence in the dental profession in China. A cross-sectional survey was carried out in 52 different hospitals in a large metropolitan city in China. A total of 304 questionnaires were distributed to respondents identified via stratified random sampling and 272 dentists (121 females and 151 males) completed the survey. The response rate was 89.5%. Visual analogue score was used to record neck and upper limb musculoskeletal symptoms on a body chart. Work-related risk factors, including physical and psychosocial factors, were accounted for in the regression analysis. 88% of the dentists reported at least one musculoskeletal disorder and 83.8% suffered from neck pain. In the multivariate analyses, working hours per day were associated with neck pain (OR=1.43; 95% CI 1.03 to 1.98). Inability to select the appropriate size of dental instrument was associated with shoulder (OR=2.07; 95% CI 1.00 to 4.32) and wrist/hand (OR=2.47; 95% CI 1.15 to 5.32) pain. As for psychosocial factors, high job demand was associated with symptoms in the shoulder (OR=1.09; 95% CI 1.00 to 1.18), elbow (OR=1.11; 95% CI 1.03 to 1.19) and wrist/hand (OR=1.09; 95% CI 1.02 to 1.17). Regular physical exercise was associated with decreased neck pain (OR=0.37; 95% CI 0.14 to 1.00). The prevalence of WMSDs among Chinese dentists is high. Specifically, long working hours, inability to select the appropriate size of dental instrument and high job demand are the most significant risk factors.


A Systematic Literature Review of Microscopy Methods Reported in Malaria Clinical Trials.
Microscopy of stained blood films is essential for the diagnosis of malaria, differentiation of parasite species, and estimation of parasite density performed for assessments of antimalarial drug efficacy. The accuracy and comparability of these measures over time and space are vital to discern the emergence or spread of antimalarial drug resistance. Although evidence-based guidelines for malaria microscopy methods exist, the age-old microscopy techniques for parasitological assessments are subject to considerable methodological variations. The purpose of this review was to explore critically how microscopy methods were reported in published malarial studies between 2013 and 2017 with the focus on outlining the methodological differences and improving reporting standards in practice.


Determinants of vitamin D levels in children, adolescents, and young adults with juvenile idiopathic arthritis.
Deficiency of 25-hydroxyvitamin D [25(OH)D] is reported to be common in patients with rheumatoid arthritis (RA); data in patients with juvenile idiopathic arthritis (JIA) are inconsistent. We assessed serum 25(OH)D in children, adolescents and young adults with JIA, in order to identify the risk factors for vitamin D deficiency in patients with JIA. We evaluated 152 patients with JIA: 115 female, 37 male, mean age 16.2 ± 7.4 yrs; evaluated by onset type, 96 had oligoarticular, 35 polyarticular, 7 systemic, and 14 enthesitis-related arthritis (ERA). Patients were compared with a control group matched for sex and age. All patients and controls underwent laboratory tests of plasma 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, and bone alkaline phosphatase levels, and dual-energy x-ray absorptiometry examination. Patients with JIA showed significantly reduced 25(OH)D levels compared to controls (p < 0.001), even divided into subtypes (oligoarticular, p < 0.05; polyarticular, p < 0.005; systemic, p < 0.001; ERA, p < 0.005). Patients with active disease and/or frequent relapses had significantly reduced 25(OH)D levels compared to patients with no active disease and no frequent flares (p < 0.005, respectively). Nevertheless, JIA patients had significantly higher PTH levels compared to controls (p < 0.0001). JIA patients with 25(OH)D deficiency showed a significantly lower bone mineral apparent density than those with normal 25(OH)D levels (p < 0.001). JIA patients have reduced 25(OH)D and higher PTH values. This may explain at least in part why JIA patients, despite more effective current drugs, do not achieve bone-normal condition over time. JIA patients with more severe disease could require higher supplementation of vitamin D to maintain normal 25(OH)D serum levels. Longterm studies are needed to investigate the relationship between serum 25(OH)D levels and disease activity in JIA.


PrP(C) association with lipid rafts in the early secretory pathway stabilizes its cellular conformation.
The pathological conversion of cellular prion protein (PrP(C)) into the scrapie prion protein (PrP(Sc)) isoform appears to have a central role in the pathogenesis of transmissible spongiform encephalopathies. However, the identity of the intracellular compartment where this conversion occurs is unknown. Several lines of evidence indicate that detergent-resistant membrane domains (DRMs or rafts) could be involved in this process. We have characterized the association of PrP(C) to rafts during its biosynthesis. We found that PrP(C) associates with rafts already as an immature precursor in the endoplasmic reticulum. Interestingly, compared with the mature protein, the immature diglycosylated form has a different susceptibility to cholesterol depletion vs. sphingolipid depletion, suggesting that the two forms associate with different lipid domains. We also found that cholesterol depletion, which affects raft-association of the immature protein, slows down protein maturation and leads to protein misfolding. On the contrary, sphingolipid depletion does not have any effect on the kinetics of protein maturation or on the conformation of the protein. These data indicate that the early association of PrP(C) with cholesterol-enriched rafts facilitates its correct folding and reinforce the hypothesis that cholesterol and sphingolipids have different roles in PrP metabolism.


Acute changes of left ventricular hemodynamics and function during percutaneous coronary intervention in patients with unprotected left main coronary artery disease.
Percutaneous coronary interventions (PCIs) are increasingly being used to treat unprotected left main coronary artery (ULMCA) lesions. However, research is sparse on the acute changes of left ventricular (LV) hemodynamics and function during PCI in patients with ULMCA stenosis. We aimed to assess the acute changes of LV function using speckle-tracking imaging during PCI in these patients. Fifteen consecutive patients who underwent elective PCI for ULMCA stenosis were enrolled. Echocardiographic studies and pressure measurement were performed at baseline, during PCI and after PCI. LMCA occlusion with a first balloon inflation induced a marked reduction in the peak positive derivative of LV pressure (dP/dt max), LV global longitudinal strain (GLS), and systolic and diastolic strain rates, and a marked increase in LV end-diastolic pressure (EDP) (all P < 0.01). During the second inflation, the degrees of LV hemodynamic and functional changes were similar to those of the first inflation, even with a higher inflation pressure. During the third inflation, the values of GLS and dP/dt max were higher than those of the second inflation (P = 0.03 and P = 0.05, respectively). After optimal PCI, dP/dt max, LVEDP, and strain parameters were improved to baseline values. LV hemodynamics and function were considerably impaired with the first ballooning during PCI for ULMCA stenosis. However, the degrees of LV hemodynamic and functional changes decreased with each successive balloon inflation, which can be explained by ischemic preconditioning. After all procedures were safely completed, LV systolic function was improved without LV diastolic stunning.


The evolution of spliced leader trans-splicing in nematodes.
Spliced leader trans-splicing occurs in many primitive eukaryotes including nematodes. Most of our knowledge of trans-splicing in nematodes stems from the model organism Caenorhabditis elegans and relatives, and from work with Ascaris. Our investigation of spliced leader trans-splicing in distantly related Dorylaimia nematodes indicates that spliced-leader trans-splicing arose before the nematode phylum and suggests that the spliced leader RNA gene complements in extant nematodes have evolved from a common ancestor with a diverse set of spliced leader RNA genes.


Live-cell-permeant thiophene fluorophores and cell-mediated formation of fluorescent fibrils.
In our search for thiophene fluorophores that can overcome the limits of currently available organic dyes in live-cell staining, we synthesized biocompatible dithienothiophene-S,S-dioxide derivatives (DTTOs) that were spontaneously taken up by live mouse embryonic fibroblasts and HeLa cells. Upon treatment with DTTOs, the cells secreted nanostructured fluorescent fibrils, while cell viability remained unaltered. Comparison with the behavior of other cell-permeant, newly synthesized thiophene fluorophores showed that the formation of fluorescent fibrils was peculiar to DTTO dyes. Laser scanning confocal microscopy of the fluorescent fibrils showed that most of them were characterized by helical supramolecular organization. Electrophoretic analysis and theoretical calculations suggested that the DTTOs were selectively recognized by the HyPro component of procollagen polypeptide chains and incorporated through the formation of multiple H-bondings.


Vaccines for preventing influenza in healthy adults.
Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America. Identify, retrieve and assess all studies evaluating the effects of vaccines against influenza in healthy adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010, issue 2), MEDLINE (January 1966 to June 2010) and EMBASE (1990 to June 2010). Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally-occurring influenza in healthy individuals aged 16 to 65 years. We also included comparative studies assessing serious and rare harms. Two review authors independently assessed trial quality and extracted data. We included 50 reports. Forty (59 sub-studies) were clinical trials of over 70,000 people. Eight were comparative non-RCTs and assessed serious harms. Two were reports of harms which could not be introduced in the data analysis. In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%, 95% confidence interval (CI) 2% to 5%). The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%). These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms and an estimated 1.6 additional cases of Guillain-Barré Syndrome per million vaccinations. The harms evidence base is limited. Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.WARNING: This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.


Characterization of the human glucocorticoid receptor promoter.
To elucidate the functional elements that are involved in the regulation of the human glucocorticoid receptor (hGR) gene, transient expression, DNase I footprinting, and gel mobility shift analyses were conducted. We found that the hGR promoter region between -700 and +38 bp contained 11 footprinted sites. Deletion of the -374 to -183 bp region, which is highly conserved between human and mouse (93%), induced a 5-24-fold reduction in promoter activity in HeLa, NIH3T3, CV1, and HepG2 cells. Three footprints, FP5, FP6, and FP7, were shown to map to this region. In particular, the FP7 site was found to be within the -374 to -347 bp region. Deletion of this region triggered a significant decline in promoter activity in HeLa and NIH3T3 cells but not in HepG2 cells. AP2 was found to bind FP7. In HepG2 cells AP2 elicited transactivation of the hGR promoter activity. Transfection data revealed that the upstream GC box-rich fragment between -700 and -375 bp induced a 4-7-fold activation of the heterologous tk promoter in an orientation-independent manner. Our studies demonstrate that several transcription factors are involved in regulating GR expression and that AP2 could function as an important positive regulator of GR promoter activity.


Granulocyte-macrophage colony-stimulating factor as adjunct therapy in relapsed lymphoid malignancy: implications for economic analyses of phase III clinical trials.
With the increasing concern over the high cost of health care, policy makers have incorporated economic analyses into phase III clinical trials as the randomized clinical trials can provide important information on the efficacy and potential cost-effectiveness of new pharmaceutical agents. Economic analyses of single-hospital experience during phase III trials of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjunct therapy for high dose chemotherapy with autologous stem cell support found significant shortening of neutropenia with GM-CSF at each hospital, but shortened hospitalization (and lower costs) at only two of three hospitals. In this study, we added data from three additional hospitals and found that the 103 patients who received GM-CSF had, on average, 5.7 days shorter durations of severe neutropenia than the 95 patients who received placebo (p < 0.0001) and 3.4 days shorter in hospitalization (p = 0.06). However, the duration of hospitalization, the primary determinant of health care costs, was shorter for GM-CSF patients in only four of the six centers and the duration of hospitalization of placebo patients was shorter at the other two centers. Careful analyses must be carried out when phase III clinical trial results are used to derive estimates of cost-effectiveness of new pharmaceutical agents. The interpretation of economic analyses of phase III clinical trials raises issues related to the perspective of the investigators, study design, collection of data on resource utilization, learning curve effects and generalizability of the results to other settings.


Assessment of RBE-Weighted Dose Models for Carbon Ion Therapy Toward Modernization of Clinical Practice at HIT: In Vitro, in Vivo, and in Patients.
Present-day treatment planning in carbon ion therapy is conducted with assumptions for a limited number of tissue types and models for effective dose. Here, we comprehensively assess relative biological effectiveness (RBE) in carbon ion therapy and associated models toward the modernization of current clinical practice in effective dose calculation. Using 2 human (A549, H460) and 2 mouse (B16, Renca) tumor cell lines, clonogenic cell survival assay was performed for examination of changes in RBE along the full range of clinical-like spread-out Bragg peak (SOBP) fields. Prediction power of the local effect model (LEM1 and LEM4) and the modified microdosimetric kinetic model (mMKM) was assessed. Experimentation and analysis were carried out in the frame of a multidimensional end point study for clinically relevant ranges of physical dose (D), dose-averaged linear energy transfer (LETd), and base-line photon radio-sensitivity (α/β)x. Additionally, predictions were compared against previously reported RBE measurements in vivo and surveyed in patient cases. RBE model prediction performance varied among the investigated perspectives, with mMKM prediction exhibiting superior agreement with measurements both in vitro and in vivo across the 3 investigated end points. LEM1 and LEM4 performed their best in the highest LET conditions but yielded overestimations and underestimations in low/midrange LET conditions, respectively, as demonstrated by comparison with measurements. Additionally, the analysis of patient treatment plans revealed substantial variability across the investigated models (±20%-30% uncertainty), largely dependent on the selected model and absolute values for input tissue parameters αx and βx. RBE dependencies in vitro, in vivo, and in silico were investigated with respect to various clinically relevant end points in the context of tumor-specific tissue radio-sensitivity assignment and accurate RBE modeling. Discovered model trends and performances advocate upgrading current treatment planning schemes in carbon ion therapy and call for verification via clinical outcome analysis with large patient cohorts.


What's new in NSAID pharmacotherapy: oral agents to injectables.
Nonsteroidal anti-inflammatory drugs (NSAIDs) represent a critically important class of medications useful in numerous musculoskeletal and inflammatory diseases. The focus of NSAID use has recently centered on gastrointestinal (GI) side effects and potential cardiovascular toxicity. Innovative new oral and intra-articular pharmaceutically engineered dosage forms are examined. We review recently developed intravenous NSAIDs and their potential advantages over oral products in the perioperative setting. Databases searched included PubMed, Google Scholar, Ovid, and Athens. We contacted key U.S. and Japanese manufactures who are developing new and innovative NSAID technologies for inclusion in this overview. Early attempts at mitigating GI toxicity with oral agents combined with gastroprotective additives are outlined. Contemporary technologies coupled with uniquely advanced pharmaceutical manipulations to improve safety and efficacy are discussed including combined vasodilating agent naproxcinod as the prototypical cyclooxygenase-inhibiting nitric oxide (NO) donor; hydrogen sulfide-releasing compounds to protect GI mucosa; glycoscience technologies combining the intra-articular hyaluronic acid SI-613 combined with NSAIDs; and nano-formulated SoluMatrix submicron technologies that include diclofenac, indomethacin, naproxen, and meloxicam. New NSAIDs under development are intended to address GI and cardiovascular pitfalls inherent to current therapy options across the entire NSAID drug class. NO or hydrogen sulfide donating drugs, new reliable injectables for perioperative and inpatient use, novel intra-articular extended-release NSAIDs combined with IAHA, and nano-formulations of submicron NSAIDs featuring delivery of decreased doses without diminished efficacy promise to afford innovative technologies that likely will be the future of NSAID therapy.


Vanishing vaccinations: why are so many Americans opting out of vaccinating their children?
Vaccinations against life-threatening diseases are one of the greatest public health achievements in history. Literally millions of premature deaths have been prevented, and countless more children have been saved from disfiguring illness. While vaccinations carry unavoidable risks, the medical, social and economic benefits they confer have led all fifty states to enact compulsory childhood vaccination laws to stop the spread of preventable diseases. Today, however, vaccines are becoming a victim of their success--many individuals have never witnessed the debilitating diseases that vaccines protect against, allowing complacency toward immunization requirements to build. Antivaccination sentiment is growing fast in the United States, in large part due to the controversial and hotly disputed link between immunizations and autism. The internet worsens fears regarding vaccination safety, as at least a dozen websites publish alarming information about the risks of vaccines. Increasing numbers of parents are refusing immunizations for their children and seeking legally sanctioned exemptions instead, apparently fearing vaccines more than the underlying diseases that they protect against. A variety of factors are at play: religious and philosophical beliefs, freedom and individualism, misinformation about risk, and overperception of risk. State legislatures and health departments now face a difficult challenge: respecting individual rights and freedoms while also safeguarding the public welfare. Nearly all states allow vaccination exemptions for religious reasons and a growing number provide "philosophical" opt-outs as well. However, in all but a handful of jurisdictions, neither objection is seriously documented or verified. Often, the law requires a parent to do no more than simply check a box indicating she does not wish her child to receive immunizations. The problem is exacerbated by financial incentives schools have to encourage students to opt out of vaccinations. The rise in parents opting out has caused the AMA grave concern, with many experts decrying the rise of so-called "exemptions of convenience." In some areas, nearly one out of five children have not received their recommended vaccines. The consequences are serious not only for those unprotected children, but for the rest of society as well. "Herd immunity" is threatened as more and more parents free ride off of the community's dwindling immunity, and outbreaks of diseases thought to have been conquered have already occurred. Lawsuits against vaccine manufacturers threaten them with bankruptcy, costs are being externalized onto the healthcare and legal systems, and vulnerable populations are suffering harm or even death. In the interests of social welfare, state legislatures and health departments should consider methods to ensure that the exemption process is carefully tailored to prevent check-the-box opt-outs of convenience, while still allowing exemptions for those with earnest and informed convictions or medical reasons.


A cerato-platanin-like protein HaCPL2 from Heterobasidion annosum sensu stricto induces cell death in Nicotiana tabacum and Pinus sylvestris.
The cerato-platanin family is a group of small secreted cysteine-rich proteins exclusive for filamentous fungi. They have been shown to be involved in the interactions between fungi and plants. Functional characterization of members from this family has been performed mainly in Ascomycota, except Moniliophthora perniciosa. Our previous phylogenetic analysis revealed that recent gene duplication of cerato-platanins has occurred in Basidiomycota but not in Ascomycota, suggesting higher functional diversification of this protein family in Basidiomycota than in Ascomycota. In this study, we identified three cerato-platanin homologues from the basidiomycete conifer pathogen Heterobasidion annosum sensu stricto. Expression of the homologues under various conditions as well as their roles in the H. annosum s.s.-Pinus sylvestris (Scots pine) pathosystem was investigated. Results showed that HaCPL2 (cerato-platanin-like protein 2) had the highest sequence similarity to cerato-platanin from Ceratocystis platani and hacpl2 was significantly induced during nutrient starvation and necrotrophic growth. The treatment with recombinant HaCPL2 induced cell death, phytoalexin production and defense gene expression in Nicotiana tabacum. Eliciting and cell death-inducing ability accompanied by retardation of apical root growth was also demonstrated in Scots pine seedlings. Our results suggest that HaCPL2 might contribute to the virulence of H. annosum s.s. by promoting plant cell death.


Can renal dimensions and the main renal artery diameter indicate the presence of an accessory renal artery? A 64-slice CT study.
To evaluate whether renal dimensions and the main renal artery (mRA) diameter can provide indirect evidence of the presence or absence of accessory renal arteries (aRA). The study group consisted of 167 patients (83 women, 84 men; mean age, 52.4±13.1 years) who presented to our radiology department for abdominal CT examinations with various indications. CT examination was performed on a 64-slice CT scanner in the arterial phase. The kidney diameters were recorded. The number of renal arteries supplying each kidney was evaluated, and their diameters were measured. We attempted to determine a formula that could be used to predict the presence or absence of aRAs. One or multiple aRAs were found in 76 (22.8%) of the 334 kidneys. The mRA diameter was 5.51±0.96 mm. The mRA diameter was smaller in kidneys with aRAs than in those without (P < 0.001). A cut-off value of 4.15 mm for the diameter of mRA to predict the presence of aRAs led to negative and positive predictive values of 80% and 90%, respectively. A formula that can predict that an aRA is absent with 97% accuracy given the values of the mRA diameter and the kidney length was determined using logistic regression. The mRA diameter (4.15 mm) alone and the results of the formula developed herein employing the mRA diameter and kidney length can respectively predict the presence or absence of an aRA with high accuracy.


Control of Taenia solium; A Case for Public and Private Sector Investment.
The zoonotic helminth T. solium is one of the leading causes of acquired epilepsy in endemic countries, resulting in a high burden both in human health and social stigma of affected people (1-3). In 2012 T. solium was highlighted as a priority for control in the World Health Assembly resolution 66.12 (4). Despite a call for validated control strategies by 2015 and a "Tool Kit" of control options being available, relatively few examples of successfully implemented and sustainable control programs are available (5-7). A minimal control strategy focusing solely on the porcine host has also been proposed although the cost-effectiveness of such has yet to be explored (8). Although acknowledgment has been made of the need for initiatives to be sustainable, we are yet to see sufficient consideration of the balance between the provision of public and private goods, and the need for engagement of the people and organizations in the pork value chains within T. solium control strategies. We utilized a food chain risk analysis model to determine the incremental cost-effectiveness ratio (ICER) in terms of $/infective meal avoided, of combining a pharmaceutical intervention in pigs with strengthened meat hygiene services. The addition of a vaccination and treatment protocol, at an additional 10.3% cost, was illustrated to have the potential to improve the ICER of improving meat inspection by 74.6%. The vaccination and treatment protocol also had the potential to reduce the losses borne by the pork industry of condemned meat by 66%, highlighting the potential to leverage private sector investment in T. solium control.


Management Practices of Cats Owned by Faculty, Staff, and Students at Two Midwest Veterinary Schools.
Understanding cat owners' housing, care, and management practices is important for promoting cat welfare. A survey study was conducted on the housing and management practices used for cats by students, faculty, and staff of The Ohio State University and Purdue University veterinary colleges. Subjects were 138 cat-owner dyads. Most cats (74%) were housed strictly indoors in keeping with common US veterinary recommendations. However, many did not implement best practices outlined for behavior and other welfare needs of indoor cats. The percentage of respondents placing resources where cats could be disrupted while using them was 31%, 53%, and 30% for resting areas, food/water dishes, and litter boxes, respectively. Many cats were not provided a litter box in a private area (35%), in multiple areas of the house (51%), or that was regularly washed (73%). Horizontal scratching opportunities were not provided to 38% of cats; 32% were not provided toys that mimic prey and 91% of cats were fed a diet consisting of >75% dry food. These findings suggest a need for more concerted efforts to educate owners about meeting their cats' welfare needs so as to attenuate risks and improve cat physical and behavioral welfare outcomes.


Transfer of maternal antibodies against avian influenza virus in mallards (Anas platyrhynchos).
Maternal antibodies protect chicks from infection with pathogens early in life and may impact pathogen dynamics due to the alteration of the proportion of susceptible individuals in a population. We investigated the transfer of maternal antibodies against avian influenza virus (AIV) in a key AIV host species, the mallard (Anas platyrhynchos). Combining observations in both the field and in mallards kept in captivity, we connected maternal AIV antibody concentrations in eggs to (i) female body condition, (ii) female AIV antibody concentration, (iii) egg laying order, (iv) egg size and (v) embryo sex. We applied maternity analysis to the eggs collected in the field to account for intraspecific nest parasitism, which is reportedly high in Anseriformes, detecting parasitic eggs in one out of eight clutches. AIV antibody prevalence in free-living and captive females was respectively 48% and 56%, with 43% and 24% of the eggs receiving these antibodies maternally. In both field and captive study, maternal AIV antibody concentrations in egg yolk correlated positively with circulating AIV antibody concentrations in females. In the captive study, yolk AIV antibody concentrations correlated positively with egg laying order. Female body mass and egg size from the field and captive study, and embryos sex from the field study were not associated with maternal AIV antibody concentrations in eggs. Our study indicates that maternal AIV antibody transfer may potentially play an important role in shaping AIV infection dynamics in mallards.


Spectrum of gluten-related disorders: consensus on new nomenclature and classification.
A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.


Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up.
The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.


Homeopathy and integrative medicine: keeping an open mind.
Some physicians have incorporated some forms of complementary and alternative medicine (CAM) or related medicinal products in their clinical practices, suggesting that an unconventional treatment approach might be seen as an integration rather than as an alternative to standard medical practice. Among the various CAMs, homeopathy enjoys growing popularity with the lay population, but it is not acknowledged by academia or included in medical guidelines. The major problem is to establish the effectiveness of this clinical approach using the strict criteria of evidence-based medicine. This issue of the Journal of Medicine and the Person collects contributions from some of the most prestigious centers and research groups working in the field of homeopathy and integrative medicine. These contributions are not specialized information but are of general interest, focusing on this discipline as one of the emerging fields of personalized medical treatment.


Factors Affecting Influenza Vaccination Rates among Patients with Chronic Obstructive Pulmonary Disease in Rize, Turkey.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are major components of COPD-related socioeconomic burden. Upper or lower respiratory tract infections, usually caused by respiratory viruses or bacteria, are common causes of AECOPD. Vaccination aganist influenza virus and Streptoccus pneumoniae, the most prevalent agents, is recommended by COPD guidelines. The aims of this study were to determine the factors affecting vaccination among patients with COPD and to assess the effect of vaccination status on AECOPD. Patients with COPD were recruited from the outpatient clinic of a tertiary hospital between December 2014 and January 2015. Demographic data, vaccination status, and COPD-related hospital admissions triggered by tracheobronchial infections were evaluated. In total, 108 patients were enrolled; 102 (94%) subjects were male, and 6 (6%) subjects were female; the mean age was 65.6 years. The number of patients who had received pneumococcal and influenza vaccinations were 8 (0.07%) and 36 (33.3%), respectively. There was no significant correlation between the level of education and vaccination status. No significant difference was found between two groups in terms of exacerbation frequency, hospitalization rates, mMRC scores, and COPD stages. More efforts by both physicians and patients are needed to reach the ideal rates of vaccination for COPD.


Implementing Eccentric Resistance Training-Part 1: A Brief Review of Existing Methods.
The purpose of this review was to provide a physiological rationale for the use of eccentric resistance training and to provide an overview of the most commonly prescribed eccentric training methods. Based on the existing literature, there is a strong physiological rationale for the incorporation of eccentric training into a training program for an individual seeking to maximize muscle size, strength, and power. Specific adaptations may include an increase in muscle cross-sectional area, force output, and fiber shortening velocities, all of which have the potential to benefit power production characteristics. Tempo eccentric training, flywheel inertial training, accentuated eccentric loading, and plyometric training are commonly implemented in applied contexts. These methods tend to involve different force absorption characteristics and thus, overload the muscle or musculotendinous unit in different ways during lengthening actions. For this reason, they may produce different magnitudes of improvement in hypertrophy, strength, and power. The constraints to which they are implemented can have a marked effect on the characteristics of force absorption and therefore, could affect the nature of the adaptive response. However, the versatility of the constraints when prescribing these methods mean that they can be effectively implemented to induce these adaptations within a variety of populations.


Responder to BNP-guided treatment in heart failure. The process of defining a responder.
B-type natriuretic peptide (BNP) levels predict prognosis and outcome in heart failure (HF) patients. To evaluate the optimal cut-off level of BNP to predict death, need for hospitalization, and worsening HF, and also to determine the optimal time to apply the chosen cut-off value. In a sub-study from the Use of PeptideS in Tailoring hEart failure Project or UPSTEP study where tailoring treatment of HF by BNP level was evaluated, we assessed the change in percentage between levels of BNP at study start versus a specific week (2, 6, 10, 16, 24, 36, or 48) during the follow-up period. The optimum cut-off percentage levels were obtained using a Cox proportional regression analysis of death, hospitalization, and worsening HF. A decrease in BNP by less than 40% in week 16 compared with study start and/or a BNP > 300 ng/L presented the highest hazard ratio (HR) for a non-responder to reach a combined endpoint (HR: 2.43; 95% confidence interval or CI: 1.61-3.65; p < 0.00003). This definition gave a 78% risk reduction of cardiovascular (CV) mortality (p > 0.0005) and an 89% risk reduction of HF mortality (p > 0.004), and reduced risk of CV and HF hospitalization for the responders. Patients with a decrease in BNP of more than 40% compared with that at study start and/or a BNP level below 300 ng/L at week 16 had a significantly reduced risk of CV and HF mortality and hospitalization.


The Effect of Head Rotation on the Relative Vascular Anatomy of the Neck: Implications for Central Venous Access.
Previous studies have shown that safe venous cannulation is difficult when the internal jugular vein (IJV) overlies the carotid artery (CA) as the probability of inadvertent arterial penetration is greatly increased. The goal of this study was to examine the anatomical relationships of the IJV and CA as a function of the degree of head rotation in order to minimize the risk for CA puncture. Our study was a prospective study using a sample of 496 Emergency Department patients. The anatomic relationships of the right and left IJVs and CAs were recorded with head rotation at three different positions. Patients who had the IJV in a 45 to 135 degree relationship to the CA were deemed to be in the high-risk zone for arterial puncture. Chi square, ANOVA. Right IJVs were in the high risk zone for 39.5%, 47.8% and 60.9% of cases at 0, 45 and 80 degrees of head rotation, respectively (P < 0.001). Left IJVs were in the high risk zone for 59.1%, 69.2% and 80.0% at 0, 45 and 80 degrees of head rotation, respectively. (P < 0.001). Head rotation should be minimized during IJV cannulation to decrease the overlap of CA by IJV. Cannulation of the left IJV appears to carry a higher degree of risk as compared to the right IJV. Placing the head in neutral position, avoiding rotation, and using ultrasound guidance are recommended to minimize complications during central venous access.


A physiologically based description of ethylene oxide dosimetry in the rat.
A physiologically based pharmacokinetic (PB-PK) model providing a quantitative description of ethylene oxide (ETO) dosimetry in the rat was developed by integrating information on physiology, tissue solubility of ETO, and rate constants for ETO metabolism and binding. The PB-PK model consisted of nine compartments; liver, lung, testis, brain, fat, venous blood, arterial blood, richly perfused and poorly perfused tissues. The tissue: air partition coefficients of ETO, determined by vial equilibration, were similar among the various tissues (range 44-83). The rate constants for glutathione (GSH) conjugation, hydrolysis, and hemoglobin (Hb)- and DNA-binding were estimated from published data and by conducting in vivo inhalation exposure studies. The model adequately predicted the concentrations of Hb and DNA adducts, hepatic and extrahepatic GSH, and urinary N-acetyl-S-(2-hydroxyethyl)-cysteine following inhalation exposures of 1.2 to 1,200 ppm and intravenous administration of 1 to 100 mg/kg of ETO in male Fischer-344 and Sprague-Dawley rats. There was no evidence of nonlinearity in the overall elimination of ETO in the dose range examined. However, nonlinearities in the components of this first order elimination process (namely GSH conjugation, hydrolysis, exhalation) were found to occur at high exposure concentrations. Characterization of the individual metabolic pathways that affect the tissue dosimetry of ETO is important for interspecies extrapolation and risk assessment for this chemical.


Intramuscular fat content in meat-producing animals: development, genetic and nutritional control, and identification of putative markers.
Intramuscular fat (IMF) content plays a key role in various quality traits of meat. IMF content varies between species, between breeds and between muscle types in the same breed. Other factors are involved in the variation of IMF content in animals, including gender, age and feeding. Variability in IMF content is mainly linked to the number and size of intramuscular adipocytes. The accretion rate of IMF depends on the muscle growth rate. For instance, animals having a high muscularity with a high glycolytic activity display a reduced development of IMF. This suggests that muscle cells and adipocytes interplay during growth. In addition, early events that influence adipogenesis inside the muscle (i.e proliferation and differentiation of adipose cells, the connective structure embedding adipocytes) might be involved in interindividual differences in IMF content. Increasing muscularity will also dilute the final fat content of muscle. At the metabolic level, IMF content results from the balance between uptake, synthesis and degradation of triacylglycerols, which involve many metabolic pathways in both adipocytes and myofibres. Various experiments revealed an association between IMF level and the muscle content in adipocyte-type fatty acid-binding protein, the activities of oxidative enzymes, or the delta-6-desaturase level; however, other studies failed to confirm such relationships. This might be due to the importance of fatty acid fluxes that is likely to be responsible for variability in IMF content during the postnatal period rather than the control of one single pathway. This is evident in the muscle of most fish species in which triacylglycerol synthesis is almost zero. Genetic approaches for increasing IMF have been focused on live animal ultrasound to derive estimated breeding values. More recently, efforts have concentrated on discovering DNA markers that change the distribution of fat in the body (i.e. towards IMF at the expense of the carcass fatness). Thanks to the exhaustive nature of genomics (transcriptomics and proteomics), our knowledge on fat accumulation in muscles is now being underpinned. Metabolic specificities of intramuscular adipocytes have also been demonstrated, as compared to other depots. Nutritional manipulation of IMF independently from body fat depots has proved to be more difficult to achieve than genetic strategies to have lipid deposition dependent of adipose tissue location. In addition, the biological mechanisms that explain the variability of IMF content differ between genetic and nutritional factors. The nutritional regulation of IMF also differs between ruminants, monogastrics and fish due to their digestive and nutritional particularities.


Resting cortical PET metabolic changes in psychogenic non-epileptic seizures (PNES).
The pathophysiology of psychogenic non-epileptic seizures (PNES) is poorly understood. Functional neuroimaging data in various functional neurological disorders increasingly support specific neurobiological dysfunction. However, to date, no studies have been reported of positron emission tomography (PET) in patients presenting with PNES. Sixteen patients being evaluated in a specialist epilepsy centre underwent PET with 2-deoxy-2-[fluorine-18]fluoro-d-glucose ((18)FDG-PET) because of suspected intractable epileptic seizures. However, in all patients, the diagnosis was subsequently confirmed to be PNES with no coexisting epilepsy. (18)FDG-PET was also performed in 16 healthy controls. A voxel by voxel intergroup analysis was performed to look for significant differences in interictal (resting state) cerebral metabolism. In addition, metabolic connectivity was studied using voxel-wise inter-regional correlation analysis. In comparison to group analysis of healthy participants, the group analysis of patients with PNES exhibited significant PET hypometabolism within the right inferior parietal and central region, and within the bilateral anterior cingulate cortex. A significant increase in metabolic correlation was found in patients with PNES, in comparison to healthy participants, between the right inferior parietal/central region and the bilateral cerebellum, and between the bilateral anterior cingulate cortex and the left parahippocampal gyrus. To the best of our knowledge, this is the first study describing FDG-PET alterations in patients with PNES. Although we cannot exclude that our data reflect changes due to comorbidities, they may indicate a dysfunction of neural systems in patients with PNES. Hypometabolism regions might relate to two of the pathophysiological mechanisms that may be involved in PNES, that is, emotional dysregulation (anterior cingulate hypometabolism) and dysfunctional processes underlying the consciousness of the self and the environment (right parietal hypometabolism). NCT00484523.


Smart strategies for doctors and doctors-in-training: heuristics in medicine.
How do doctors make sound decisions when confronted with probabilistic data, time pressures and a heavy workload? One theory that has been embraced by many researchers is based on optimisation, which emphasises the need to integrate all information in order to arrive at sound decisions. This notion makes heuristics, which use less than complete information, appear as second-best strategies. In this article, we challenge this pessimistic view of heuristics. We introduce two medical problems that involve decision making to the reader: one concerns coronary care issues and the other macrolide prescriptions. In both settings, decision-making tools grounded in the principles of optimisation and heuristics, respectively, have been developed to assist doctors in making decisions. We explain the structure of each of these tools and compare their performance in terms of their facilitation of correct predictions. For decisions concerning both the coronary care unit and the prescribing of macrolides, we demonstrate that sacrificing information does not necessarily imply a forfeiting of predictive accuracy, but can sometimes even lead to better decisions. Subsequently, we discuss common misconceptions about heuristics and explain when and why ignoring parts of the available information can lead to the making of more robust predictions. Heuristics are neither good nor bad per se, but, if applied in situations to which they have been adapted, can be helpful companions for doctors and doctors-in-training. This, however, requires that heuristics in medicine be openly discussed, criticised, refined and then taught to doctors-in-training rather than being simply dismissed as harmful or irrelevant. A more uniform use of explicit and accepted heuristics has the potential to reduce variations in diagnoses and to improve medical care for patients.


Sperm global DNA methylation level: association with semen parameters and genome integrity.
Sperm DNA methylation abnormalities have been detected in oligozoospermic men. However, the association between sperm DNA methylation defects, sperm parameters and sperm DNA, and chromatin integrity remains poorly understood. This study was designed to clarify this issue. We recruited a cohort of 92 men (62 normozoospermic and 30 oligoasthenozoospermic) presenting for infertility evaluation during a 1-year period. Sperm global DNA methylation was evaluated by an ELISA-like method, DNA fragmentation was evaluated by flow cytometry-based terminal transferase dUTP nick end-labeling (TUNEL) assay (reported as DNA fragmentation index or DFI), and sperm denaturation was evaluated by aniline blue staining (reported as sperm denaturation index or SDI, a marker of chromatin compaction). We found a significant positive association between sperm global DNA methylation level and conventional sperm parameters (sperm concentration and motility), supported by the results of methylation analysis on H19-DMR. We also identified significant inverse relationships between sperm global DNA methylation, and, both DFI and SDI. However, sperm global DNA methylation level was not related to sperm vitality or morphology. Our findings suggest that global sperm DNA methylation levels are related to conventional sperm parameters, as well as, sperm chromatin and DNA integrity.


Plasmodium vivax sub-patent infections after radical treatment are common in Peruvian patients: results of a 1-year prospective cohort study.
There is an increasing body of literature reporting treatment failure of the currently recommended radical treatment of Plasmodium vivax infections. As P. vivax is the main malaria species outside the African continent, emerging tolerance to its radical treatment regime could have major consequences in countries like Peru, where 80% of malaria cases are due to P. vivax. Here we describe the results of a 1-year longitudinal follow up of 51 confirmed P. vivax patients living around Iquitos, Peruvian Amazon, and treated according to the Peruvian national guidelines. Each month a blood sample for microscopy and later genotyping was systematically collected. Recent exposure to infection was estimated by detecting antibodies against the P. vivax circumsporozoite protein (CSP) and all PCR confirmed P. vivax infections were genotyped with 16 polymorphic microsatellites. During a 1-year period, 84 recurrent infections, 22 positive also by microscopy, were identified, with a median survival time to first recurrent infection of 203 days. Most of them (71%) were asymptomatic; in 13 patients the infection persisted undetected by microscopy for several consecutive months. The genotype of mostly recurrent infections differed from that at day 0 while fewer differences were seen between the recurrent infections. The average expected heterozygosity was 0.56. There was strong linkage disequilibrium (I(A)(s) = 0.29, p<1.10(-4)) that remained also when analyzing only the unique haplotypes, suggesting common inbreeding. In Peru, the P. vivax recurrent infections were common and displayed a high turnover of parasite genotypes compared to day 0. Plasmodium vivax patients, even when treated according to the national guidelines, may still represent an important parasite reservoir that can maintain transmission. Any elimination effort should consider such a hidden reservoir.


Microarray-based identification of individual HERV loci expression: application to biomarker discovery in prostate cancer.
The prostate-specific antigen (PSA) is the main diagnostic biomarker for prostate cancer in clinical use, but it lacks specificity and sensitivity, particularly in low dosage values(1). 'How to use PSA' remains a current issue, either for diagnosis as a gray zone corresponding to a concentration in serum of 2.5-10 ng/ml which does not allow a clear differentiation to be made between cancer and noncancer(2) or for patient follow-up as analysis of post-operative PSA kinetic parameters can pose considerable challenges for their practical application(3,4). Alternatively, noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease, e.g. PCA3 in prostate cancer(5,6) and to reveal uncharacterized aspects of tumor biology. Moreover, data from the ENCODE project published in 2012 showed that different RNA types cover about 62% of the genome. It also appears that the amount of transcriptional regulatory motifs is at least 4.5x higher than the one corresponding to protein-coding exons. Thus, long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) constitute a wide range of putative/candidate transcriptional regulatory sequences, as it is their primary function in infectious retroviruses. HERVs, which are spread throughout the human genome, originate from ancestral and independent infections within the germ line, followed by copy-paste propagation processes and leading to multicopy families occupying 8% of the human genome (note that exons span 2% of our genome). Some HERV loci still express proteins that have been associated with several pathologies including cancer(7-10). We have designed a high-density microarray, in Affymetrix format, aiming to optimally characterize individual HERV loci expression, in order to better understand whether they can be active, if they drive ncRNA transcription or modulate coding gene expression. This tool has been applied in the prostate cancer field (Figure 1).


Elevated salivary alpha amylase in adolescent sexual abuse survivors with posttraumatic stress disorder symptoms.
Little is known regarding neuroendocrine responses in adolescent girls with posttraumatic stress disorder (PTSD) who have experienced sexual abuse. Therefore, we collected saliva samples three times daily for 3 days to assess concentrations of salivary alpha amylase (sAA) - a surrogate marker for autonomic nervous system (ANS) activity and, in particular, sympathetic activity - in sexually abused adolescent girls. Twenty-four girls (mean age: 15±1.4 years) who had experienced recent sexual abuse (i.e., sexual abuse occurred 1-6 months prior to study enrollment) and 12 healthy comparison subjects (mean age: 14.8±1.3 years) completed a structured interview and assessments to ascertain symptoms of posttraumatic stress, then collected saliva at home upon awakening, 30 minutes after waking, and at 5 p.m. on three consecutive school days. For sexually abused girls, total PTSD symptoms were associated with higher overall morning levels of sAA (r[20]=0.51, p=0.02), a finding driven by intrusive symptoms (r[20]=0.43, p<0.05) and hyperarousal symptoms (r[20]=0.58, p=0.01). There were no significant differences in diurnal sAA secretion between the sexually abused girls and healthy comparison adolescents. Overall morning concentrations of sAA in sexually abused girls are associated with overall PTSD severity as well as symptoms of hyperarousal and intrusive symptoms, possibly reflecting symptom-linked increases in ANS tone. These data raise the possibility that alterations in ANS activity are related to the pathophysiology of sexual abuse-related PTSD in adolescent girls, and may inform therapeutic interventions (e.g., antiadrenergic medications).


Movement-related coupling of human subthalamic nucleus spikes to cortical gamma.
Cortico-basal ganglia interactions continuously shape the way we move. Ideas about how this circuit works are based largely on models those consider only firing rate as the mechanism of information transfer. A distinct feature of neural activity accompanying movement, however, is increased motor cortical and basal ganglia gamma synchrony. To investigate the relationship between neuronal firing in the basal ganglia and cortical gamma activity during movement, we analysed human ECoG and subthalamic nucleus (STN) unit activity during hand gripping. We found that fast reaction times were preceded by enhanced STN spike-to-cortical gamma phase coupling, indicating a role in motor preparation. Importantly, increased gamma phase coupling occurred independent of changes in mean STN firing rates, and the relative timing of STN spikes was offset by half a gamma cycle for ipsilateral vs. contralateral movements, indicating that relative spike timing is as relevant as firing rate for understanding cortico-basal ganglia information transfer.


Chlamydial DNA is absent from the joints of patients with sexually acquired reactive arthritis.
The polymerase chain reaction was used to detect the presence of a plasmid essential for the growth of Chlamydia trachomatis. As few as 10 copies of the plasmid in the initial reaction mix were detectable using this technique. In contrast, chlamydial DNA was not detectable in the knee joints of nine patients with definite sexually acquired reactive arthritis (SARA) or nine patients with suspected SARA. Five patients with an undifferentiated seronegative lower limb oligoarthropathy, one with Crohn's disease and another with post-enteric reactive arthritis had evidence of intra-articular chlamydial antigens as judged by fluorescein-labelled monoclonal antibody staining of joint material but, again, no chlamydia plasmid DNA was detected. The nature of the immunofluorescent staining seen in some of these samples remains to be elucidated. It could be due to the presence of chlamydial outer membrane protein or lipopolysaccharide antigens in the joints, either free or in immune complexes, or it may be artefactual. Our results indicate that viable C. trachomatis is not present in the joints of the patients in this study even in the presence of chlamydial antigen detected by fluorescence antibody testing.


Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients.
This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39-7.42), p 0.006; HR 18.28 (2.80-119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.


Oral administration of a hydrophilic extract of Polypodium leucotomos for the prevention of polymorphic light eruption.
Polymorphic light eruption (PLE) is the most common idiopathic photodermatosis. Reactive oxygen species have been implicated in the pathogenesis of PLE. Polypodium leucotomos (PL) is a natural extract from tropical fern leaves with potent antioxidant and anti-inflammatory properties. In this study we sought to evaluate whether a concentrated hydrophilic extract of PL might prevent or delay the photoinduction of typical PLE lesions by artificial ultraviolet (UV) radiation. A total of 35 patients with long-standing PLE were included in this open, uncontrolled bicenter study. PLE was induced by photoprovocation with artificial UVB and UVA light, thereafter oral treatment with PL was initiated. Two weeks later a second photoprovocation was performed while the patients were still taking PL. Thirty patients developed PLE lesions after repeated irradiation with UVA. Of these, 18 patients also responded to UVB. After PL treatment, 9 (30%) and 5 (28%) patients, respectively, were unresponsive to repeated UVA and UVB exposure. In the remaining patients, the mean number of UVA and UVB irradiations required to elicit PLE increased significantly from 1.95 to 2.62 (P = .005) and from 2.38 to 2.92 (P = .047), respectively. The study was open and uncontrolled and included a relatively small number of patients. Our data indicate that oral PL treatment might be beneficial for the prevention of PLE.


A 15-year review of midface reconstruction after total and subtotal maxillectomy: part I. Algorithm and outcomes.
Reconstruction of complex midfacial defects is best approached with a clear algorithm. The goals of reconstruction are functional and aesthetic. Over a 15-year period (1992 to 2006), a single surgeon (P.G.C.) performed 100 flaps to reconstruct the following midfacial defects: type I, limited maxillectomy (n = 20); type IIA, subtotal maxillectomy with resection of less than 50 percent of the palate (n = 8); type IIB, subtotal maxillectomy with resection of greater than 50 percent of the palate (n = 8); type IIIA, total maxillectomy with preservation of the orbital contents (n = 22); type IIIB, total maxillectomy with orbital exenteration (n = 23); and type IV, orbitomaxillectomy (n = 19). Free flaps were used in 94 cases (94 percent), and pedicled flaps were used in six (6 percent). One hundred flaps were performed in 96 patients (69 males, 72 percent; 27 females, 28 percent); four patients underwent a second flap reconstruction due to recurrent disease (n = 4, 4 percent). Average patient age was 49.2 years (range, 13 to 81 years). Free-flap survival was 100 percent, with one partial flap loss (1 percent). Five patients suffered systemic complications (5.2 percent), and four died within 30 days of hospitalization (4.2 percent). Over 50 percent of patients returned to normal diet and speech. Almost 60 percent were judged to have an excellent aesthetic result. Free-tissue transfer offers the most effective and reliable form of reconstruction for complex maxillectomy defects. Rectus abdominis and radial forearm free flaps in combination with immediate bone grafting or as osteocutaneous flaps consistently provide the best functional and aesthetic results. Therapeutic, IV.


CNARA: reliability assessment for genomic copy number profiles.
DNA copy number profiles from microarray and sequencing experiments sometimes contain wave artefacts which may be introduced during sample preparation and cannot be removed completely by existing preprocessing methods. Besides, large derivative log ratio spread (DLRS) of the probes correlating with poor DNA quality is sometimes observed in genome screening experiments and may lead to unreliable copy number profiles. Depending on the extent of these artefacts and the resulting misidentification of copy number alterations/variations (CNA/CNV), it may be desirable to exclude such samples from analyses or to adapt the downstream data analysis strategy accordingly. Here, we propose a method to distinguish reliable genomic copy number profiles from those containing heavy wave artefacts and/or large DLRS. We define four features that adequately summarize the copy number profiles for reliability assessment, and train a classifier on a dataset of 1522 copy number profiles from various microarray platforms. The method can be applied to predict the reliability of copy number profiles irrespective of the underlying microarray platform and may be adapted for those sequencing platforms from which copy number estimates could be computed as a piecewise constant signal. Further details can be found at https://github.com/baudisgroup/CNARA . We have developed a method for the assessment of genomic copy number profiling data, and suggest to apply the method in addition to and after other state-of-the-art noise correction and quality control procedures. CNARA could be instrumental in improving the assessment of data used for genomic data mining experiments and support the reliable functional attribution of copy number aberrations especially in cancer research.


Contractility in mammalian heart muscle; calcium and osmolality.
The influence of osmolality of the external medium on the calcium (Ca) dependency of contractility of isolated electrically excited cat papillary muscle was examined. Maximum unloaded velocity of shortening was directly measured by load clamping the muscle from the preload (at the length, Lmax, at which maximum active tension was developed) to zero load (zero load clamp). Peak velocity of shortening at the Lmax preload, peak total force, peak rate of force development, time to peak force, and time to half relaxation were also recorded. The performance-Ca response curves (Ca concentration between 1.25 nM and 10 nM) for maximum unloaded velocity of shortening, peak shortening velocity at Lmax preload, total force, and peak rate of force development were shifted to the left when osmolality was increased (from 290 mosmoles to 410 mosmoles) with sucrose, and to the right when osmolality was increased with NaCl. The sensitivity for Ca, as determined from the slopes of these response curves, appeared essentially unaltered by either sucrose or NaCl, except for the high Ca concentrations (above 5 mM) at the higher osmolalities (above 370 mosmoles) especially with sucrose.