Early loading of plalatal implants (ortho-type II) a prospective multicenter randomized controlled clinical trial.
In orthodontic treatment, anchorage control is a fundamental aspect. Usually conventional mechanism for orthodontic anchorage control can be either extraoral or intraoral that is headgear or intermaxillary elastics. Their use are combined with various side effects such as tipping of occlusal plane or undesirable movements of teeth. Especially in cases, where key-teeth are missing, conventional anchorage defined as tooth-borne anchorage will meet limitations. Therefore, the use of endosseous implants for anchorage purposes are increasingly used to achieve positional stability and maximum anchorage. The intended study is designed as a prospective, multicenter randomized controlled trial (RCT), comparing and contrasting the effect of early loading of palatal implant therapy versus implant loading after 12 weeks post implantation using the new ortho-implant type II anchor system device (Orthosystem Straumann, Basel, Switzerland). 124 participants, mainly adult males or females, whose diagnoses require temporary stationary implant-based anchorage treatment will be randomized 1:1 to one of two treatment groups: group 1 will receive a loading of implant standard therapy after a healing period of 12 week (gold standard), whereas group 2 will receive an early loading of orthodontic implants within 1 week after implant insertion. Participants will be at least followed for 12 months after implant placement. The primary endpoint is to investigate the behavior of early loaded palatal implants in order to find out if shorter healing periods might be justified to accelerate active orthodontic treatment. Secondary outcomes will focus e.g. on achievement of orthodontic treatment goals and quantity of direct implant-bone interface of removed bone specimens. As tertiary objective, a histologic and microtomography evaluation of all retrieved implants will be performed to obtain data on the performance of the SLA surface in human bone evaluation of all retrieved implants. Additionally, resonance frequency analysis (RFA, Osstell mentor) will be used at different times for clinically monitoring the implant stability and for histological comparison in order to measure the reliability of the resonance frequency measuring device. Current Controlled Trials ISRCTN97142521.


Atherosclerotic Cardiovascular Disease Risk Prediction in Disaggregated Asian and Hispanic Subgroups Using Electronic Health Records.
Background Risk assessment is the cornerstone for atherosclerotic cardiovascular disease ( ASCVD ) treatment decisions. The Pooled Cohort Equations ( PCE ) have not been validated in disaggregated Asian or Hispanic populations, who have heterogeneous cardiovascular risk and outcomes. Methods and Results We used electronic health record data from adults aged 40 to 79 years from a community-based, outpatient healthcare system in northern California between January 1, 2006 and December 31, 2015, without ASCVD and not on statins. We examined the calibration and discrimination of the PCE and recalibrated the equations for disaggregated race/ethnic subgroups. The cohort included 231 622 adults with a mean age of 53.1 (SD 9.7) years and 54.3% women. There were 56 130 Asian (Chinese, Asian Indian, Filipino, Japanese, Vietnamese, and other Asian) and 19 760 Hispanic (Mexican, Puerto Rican, and other Hispanic) patients. There were 2703 events (332 and 189 in Asian and Hispanic patients, respectively) during an average of 3.9 (SD 1.5) years of follow-up. The PCE overestimated risk for NHW s, African Americans, Asians, and Hispanics by 20% to 60%. The extent of overestimation of ASCVD risk varied by disaggregated racial/ethnic subgroups, with a predicted-to-observed ratio of ASCVD events ranging from 1.1 for Puerto Rican patients to 1.9 for Chinese patients. The PCE had adequate discrimination, although it varied significantly by race/ethnic subgroups (C-indices 0.66-0.83). Recalibration of the PCE did not significantly improve its performance. Conclusions Using electronic health record data from a large, real-world population, we found that the PCE generally overestimated ASCVD risk, with marked heterogeneity by disaggregated Asian and Hispanic subgroups.


[Nursing and its reliance on self-care: emancipatory investments or practices of submission?].
The paper aimed at reflecting on the prevalence of self-care as a possible and desirable result of nursing education enterprises which focus on individual autonomy for one's own care. It can be argued that, in such a context, the teaching toward self-care has been directed according to technical orientations and biased definitions of "being healthy", of what it means to "be autonomous" and the meanings of "taking care of oneself". In this sense, taking into account the premises of health promotion, one questions the potential for self-care teaching to be liberating and to promote autonomy. One asks whether this could be more of a case of yet another investment on the submission of subjects than an action that promotes emancipation. The conclusion proposes "listening" as an alternative for minimizing the dilemmas produced in this context.


T-cell receptor beta variable region diversity in melanoma metastases after interleukin 2-based immunotherapy.
Limited T-cell receptor (TCR) repertoire of tumor-infiltrating lymphocytes has been found in melanoma metastases and spontaneously regressing melanoma. Immunotherapy with INF-alpha/interleukin 2 can induce tumor regression in a proportion of patients with metastatic melanoma. We analyzed the gene expression of the TCR-beta variable (Vbeta) region of tumor-infiltrating lymphocytes from 16 melanoma metastases by subgroup-specific semiquantitative RNA PCR to investigate the influence of immunotherapy on the TCR pattern. In five progressing metastases before or after immunotherapy, no overexpression of Vbeta gene families was detectable, whereas in seven of seven metastases responding to IFN-alpha/interleukin 2 one to four Vbeta gene families were overexpressed. Preferential usage of certain Vbeta gene subgroups in patients sharing the same HLA class I molecules suggests a T-cell response to dominant public epitopes. Analysis of multiple specimens from the same patients gives evidence that this strong oligoclonal T-cell selection is induced or at least augmented by immunotherapy, supporting the functional relevance of this finding.


Inhibitors of apoptosis protect the ovarian reserve from cyclophosphamide.
Cancer therapy can cause off-target effects including ovarian damage, which may result in primary ovarian insufficiency in girls and premenopausal women. Loss of ovarian follicles within the ovarian reserve leads to ovarian endocrine dysfunction and impaired fertility. Cyclophosphamide (CPA), a commonly used chemotherapeutic and immunosuppressant agent, is a gonadotoxic agent that destroys ovarian cells by crosslinking DNA. To protect the ovary against CPA damage, we sought to precisely map the mechanism by which the ovarian reserve is depleted by CPA. We found that CPA specifically depletes primordial follicles without affecting primary and secondary follicles in three independent murine strains (CD-1, C57BL/6J and BALB/cJ) in vivo. We directly tested the effect of the active metabolite of CPA, 1 μM 4-hydroxyperoxycyclophophamide (4-HC), in vitro and confirmed the loss of primordial oocytes but no change in the number of primary and secondary follicles. We demonstrated that phospho-AKT (p-AKT) and cleaved PARP (cPARP) are present in primordial oocytes 3 days after CPA injection, consistent with the role of these markers as part of the apoptotic cascade. Interestingly, p-AKT positive primordial oocytes co-expressed cPARP. Treatment of animals with specific inhibitors of apoptotic pathway components, ETP46464 and CHK2, blocked 4-HC‒induced DNA damage in vitro. These data suggest that CPA targets primordial germ cells in the ovarian reserve by stimulating apoptosis pathways. Adjuvant therapies to protect primordial germ cells from the off-target effects of CPA may reduce the risk of POI.


The rationale and plan for creating a World Antimalarial Resistance Network (WARN).
Drug resistant malaria was a major factor contributing to the failure of a worldwide campaign to eradicate malaria in the last century, and now threatens the large investment being made by the global community in the rollout of effective new drug combinations to replace failed drugs. Four related papers in this issue of Malaria Journal make the case for creating the World Antimalarial Resistance Network (WARN), which will consist of four linked open-access global databases containing clinical, in vitro, molecular and pharmacological data, and networks of reference laboratories that will support these databases and related surveillance activities. WARN will serve as a public resource to guide antimalarial drug treatment and prevention policies and to help confirm and characterize the new emergence of new resistance to antimalarial drugs and to contain its spread.


CARE Scale-7: Development and Preliminary Validation of a Measure to Assess Factors Impacting Self-Care in Chronic Pain.
Social and interpersonal factors may impact chronic pain self-care and self-management; however, no integrated measure exists to assess the interplay of these factors. We developed and tested a measure designed to assess salient interpersonal factors, including relationship guilt and worry, and difficulty prioritizing self-care in chronic pain. We tested self-report items broadly relevant to locus of care, limit-setting capacity, and worry/guilt about relationships in 3 discrete chronic pain samples (total N=1,452): (1) online sample of chronic pain clinic patients (N=729; 21 candidate CARE items, sociodemographics, and measures of psychological and physical functioning). Analytic results supported a final 7-item CARE scale that was next tested in (2) an anonymous online sample of 578 adults with chronic pain. (3) Finally, preliminary validation of the CARE scale was performed in a tertiary pain clinic sample (N=145). Exploratory factor analysis revealed a 7-item, 2-factor solution (difficulty prioritizing self-care and guilt/worry) that accounted for a combined total of 58% of the variance. CARE scale-7 had modest convergent validity with pain intensity, pain-related interference, and emotional distress. Extreme difficulty with both factors was reported by about one-third of the total sample, suggesting that relationship factors significantly impact pain management and self-care. Social factors are gaining attention for their influence on the trajectory of chronic pain. The CARE scale is a brief, integrated measure that may be used to reveal specific interpersonal and personal impediments to self-care, and identify important therapeutic targets to optimize self-management behaviors.


Universal tight binding model for chemical reactions in solution and at surfaces. II. Water.
A revised water model intended for use in condensed phase simulations in the framework of the self consistent polarizable ion tight binding theory is constructed. The model is applied to water monomer, dimer, hexamers, ice, and liquid, where it demonstrates good agreement with theoretical results obtained by more accurate methods, such as DFT and CCSD(T), and with experiment. In particular, the temperature dependence of the self diffusion coefficient in liquid water predicted by the model, closely reproduces experimental curves in the temperature interval between 230 K and 350 K. In addition, and in contrast to standard DFT, the model properly orders the relative densities of liquid water and ice. A notable, but inevitable, shortcoming of the model is underestimation of the static dielectric constant by a factor of two. We demonstrate that the description of inter and intramolecular forces embodied in the tight binding approximation in quantum mechanics leads to a number of valuable insights which can be missing from ab initio quantum chemistry and classical force fields. These include a discussion of the origin of the enhanced molecular electric dipole moment in the condensed phases, and a detailed explanation for the increase of coordination number in liquid water as a function of temperature and compared with ice--leading to insights into the anomalous expansion on freezing. The theory holds out the prospect of an understanding of the currently unexplained density maximum of water near the freezing point.


Symptomatic gastro-oesophageal reflux, abnormal oesophageal acid exposure, and mucosal acid sensitivity are three separate, though related, aspects of gastro-oesophageal reflux disease.
The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient's usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 'gastro-oesophageal reflux disease' are absent, or who do not have symptoms during pH monitoring.


Performance of first mammography examination in women younger than 40 years.
Few data have been published on mammography performance in women who are younger than 40 years. We pooled data from six mammography registries across the United States from the Breast Cancer Surveillance Consortium. We included 117 738 women who were aged 18-39 years when they had their first screening or diagnostic mammogram during 1995-2005 and followed them for 1 year to determine accuracy of mammography assessment. We measured the recall rate for screening examinations and the sensitivity, specificity, positive predictive value, and cancer detection rate for all mammograms. For screening mammograms, no cancers were detected in 637 mammograms for women aged 18-24 years. For women aged 35-39 years who had the largest number of screening mammograms (n = 73 335) in this study, the recall rate was 12.7% (95% confidence interval [CI] = 12.4% to 12.9%), sensitivity was 76.1% (95% CI = 69.2% to 82.6%), specificity was 87.5% (95% CI = 87.2% to 87.7%), positive predictive value was 1.3% (95% CI = 1.1% to 1.5%), and cancer detection rate was 1.6 cancers per 1000 mammograms (95% CI = 1.3 to 1.9 cancers per 1000 mammograms). Most (67 468 [77.7%]) of the 86 871 women screened reported no family history of breast cancer. For diagnostic mammograms, the age-adjusted rates across all age groups were: sensitivity of 85.7% (95% CI = 82.7% to 88.7%), specificity of 88.8% (95% CI = 88.4% to 89.1%), positive predictive value of 14.6% (95% CI = 13.3% to 15.8%), and cancer detection rate of 14.3 cancers per 1000 mammograms (95% CI = 13.0 to 15.7 cancers per 1000 mammograms). Mammography performance, except for specificity, improved in the presence of a breast lump. Younger women have very low breast cancer rates but after mammography experience high recall rates, high rates of additional imaging, and low cancer detection rates. We found no cancers in women younger than 25 years and poor performance for the large group of women aged 35-39 years. In a theoretical population of 10 000 women aged 35-39 years, 1266 women who are screened will receive further workup, with 16 cancers detected and 1250 women receiving a false-positive result.


WE-G-213CD-06: Implementation of Real-Time Tumor Tracking Using Robotic Couch.
The purpose of this study was to present a novel method for real- time tumor tracking using a commercially available robotic treatment couch, and to evaluate tumor tracking accuracy. Commercially available robotic couches are capable of positioning patients with high level of accuracy; however, currently there is no provision for compensating tumor motion using these systems. Elekta's existing commercial couch (PreciseTM Table) was used without changing its design. To establish the real-time couch motion for tracking, a novel control system was developed and implemented. The tabletop could be moved in horizontal plane (laterally and longitudinally) using two Maxon-24V motors with gearbox combination. Vertical motion was obtained using robust 70V-Rockwell Automation motor. For vertical motor position sensing, we used Model 755A-Accu- Coder encoder. Two Baumer-ITD_01_4mm shaft encoders were used for the lateral and longitudinal motions of the couch. Motors were connected to the Advance Motion Controls (AMC) amplifiers: for the vertical motion, motor AMC-20A20-INV amplifier was used, and two AMC-Z6A8 amplifiers were applied for the lateral and longitudinal couch motions. The Galil DMC-4133 controller was connected to standard PC computer using USB port. The system had two independent power supplies: Galil PSR-12- 24-12A, 24vdc power supply with diodes for controller and 24vdc motors and amplifiers, and Galil-PS300W72 72vdc power supply for vertical motion. Control algorithms were developed for position and velocity adjustment. The system was tested for real-time tracking in the range of 50mm in all 3 directions (superior-inferior, lateral, anterior- posterior). Accuracies were 0.15, 0.20, and 0.18mm, respectively. Repeatability of the desired motion was within ± 0.2mm. Experimental results of couch tracking show feasibility of real-time tumor tracking with high level of accuracy (within sub-millimeter range). This tracking technique potentially offers a simple and effective method to minimize healthy tissues irradiation.Acknowledgement: Study supported by Elekta,Ltd. Study supported by Elekta, Ltd.


STUDIES ON EXPERIMENTAL HYPERTENSION : I. THE PRODUCTION OF PERSISTENT ELEVATION OF SYSTOLIC BLOOD PRESSURE BY MEANS OF RENAL ISCHEMIA.
These experiments indicate that, in dogs at least, ischemia localized to the kidneys is a sufficient condition for the production of persistently elevated systolic blood pressure. When the constriction of both main renal arteries is made only moderately severe in the beginning, the elevation of systolic blood pressure is unaccompanied by signs of materially decreased renal function. In this respect the hypertension in these animals resembles the hypertension which is associated with so called benign nephrosclerosis in man. Subsequent increase of the constriction of the main renal arteries does not materially damage renal function, probably because of adequate development of accessory circulation. More delicate methods for detecting a change may yet prove that some damage does occur. Almost complete constriction of both main renal arteries, from the beginning, results in great elevation of systolic blood pressure which is accompanied by severe disturbance of renal function and uremia. This resembles the type of hypertension which is associated with so called malignant nephrosclerosis, in the sense of Fahr (17). In several of the animals with persistent elevation of systolic blood pressure, anatomical changes were observed in the glomeruli, vessels and parenchyma of the kidneys which are most probably directly referable to the ischemia. It is hoped that these investigations will afford a means of studying the pathogenesis of hypertension that is associated with renal vascular disease.


Molecular Aspects of Conifer Zygotic and Somatic Embryo Development: A Review of Genome-Wide Approaches and Recent Insights.
Genome-wide profiling (transcriptomics, proteomics, metabolomics) is providing unprecedented opportunities to unravel the complexity of coordinated gene expression during embryo development in trees, especially conifer species harboring "giga-genome." This knowledge should be critical for the efficient delivery of improved varieties through seeds and/or somatic embryos in fluctuating markets and to cope with climate change. We reviewed "omics" as well as targeted gene expression studies during both somatic and zygotic embryo development in conifers and tentatively puzzled over the critical processes and genes involved at the specific developmental and transition stages. Current limitations to the interpretation of these large datasets are going to be lifted through the ongoing development of comprehensive genome resources in conifers. Nevertheless omics already confirmed that master regulators (e.g., transcription and epigenetic factors) play central roles. As in model angiosperms, the molecular regulation from early to late embryogenesis may mainly arise from spatiotemporal modulation of auxin-, gibberellin-, and abscisic acid-mediated responses. Omics also showed the potential for the development of tools to assess the progress of embryo development or to build genotype-independent, predictive models of embryogenesis-specific characteristics.


Measuring very low optical powers with a common camera.
We introduce a procedure to calibrate an inexpensive, commercial camera for optical power measurements. This allows the use of the camera as a very sensitive optical power meter that is able to measure powers down to the femtowatt level. A windowing technique, based on the selection of a region of interest from the total sensor area, is used to maintain a good signal-to-noise ratio over a large range of the measured optical powers. The increase of the exposure time of the camera shifts its detection limit to lower powers. Using this calibration procedure and the windowing technique, we measured 25 fW of optical power with a common complementary metal-oxide-semiconductor camera.


The value of CSF adenosine deaminase levels in the differential diagnosis of childhood meningitis.
In this study, adenosine deaminase (ADA) levels of serum and cerebrospinal fluid (CSF) in a total 28 children (13 with bacterial meningitis, 5 with mumps meningoencephalitis and 10 with febrile convulsions) were determined. The comparisons between the serum values were insignificant (p greater than 0.05) but the CSF levels of the children with bacterial meningitis were higher than in the others (p less than 0.05). These findings suggest that serum ADA levels are not important in the diagnosis and differential diagnosis of these diseases. However, ADA levels of CSF may be useful in differentiating between bacterial and viral meningitis.


Low temperature crystallisation of mesoporous TiO2.
Conducting mesoporous TiO2 is rapidly gaining importance for green energy applications. To optimise performance, its porosity and crystallinity must be carefully fine-tuned. To this end, we have performed a detailed study on the temperature dependence of TiO2 crystallisation in mesoporous films. Crystal nucleation and growth of initially amorphous TiO2 derived by hydrolytic sol-gel chemistry is compared to the evolution of crystallinity from nanocrystalline building blocks obtained from non-hydrolytic sol-gel chemistry, and mixtures thereof. Our study addresses the question whether the critical temperature for crystal growth can be lowered by the addition of crystalline nucleation seeds.


Mapping thalamocortical networks in rat brain using resting-state functional connectivity.
Thalamocortical connectivity plays a vital role in brain function. The anatomy and function of thalamocortical networks have been extensively studied in animals by numerous invasive techniques. Non-invasively mapping thalamocortical networks in humans has also been demonstrated by utilizing resting-state functional magnetic resonance imaging (rsfMRI). However, success in simultaneously imaging multiple thalamocortical networks in animals is rather limited. This is largely due to the profound impact of anesthesia used in most animal experiments on functional connectivity measurement. Here we have employed an awake animal imaging approach to systematically map thalamocortical connectivity for multiple thalamic nuclei in rats. Seed-based correlational analysis demonstrated robust functional connectivity for each thalamic nucleus in the cortex, and the cortical connectivity profiles revealed were in excellent accordance with the known thalamocortical anatomical connections. In addition, partial correlation analysis was utilized to further improve the spatial specificity of thalamocortical connectivity. Taken together, these findings have provided important evidence supporting the validity of rsfMRI measurement in awake animals. More importantly, the present study has made it possible to non-invasively investigate the function, neuroplasticity and mutual interactions of thalamocortical networks in animal models.


Extraction of Data from a Hospital Information System to Perform Process Mining.
The aim of this work is to share our experience in relevant data extraction from a hospital information system in preparation for a research study using process mining techniques. The steps performed were: research definition, mapping the normative processes, identification of tables and fields names of the database, and extraction of data. We then offer lessons learned during data extraction phase. Any errors made in the extraction phase will propagate and have implications on subsequent analyses. Thus, it is essential to take the time needed and devote sufficient attention to detail to perform all activities with the goal of ensuring high quality of the extracted data. We hope this work will be informative for other researchers to plan and execute extraction of data for process mining research studies.


Preparing nurses to prescribe medicines for patients with dermatological conditions.
From Spring 2006, independent extended nurse prescribers in the United Kingdom will be able to prescribe any licensed medicines except controlled drugs. Supplementary nurse prescribers are currently able to prescribe any medication. No other country in the world has such extended prescribing rights for nurses. Aspects of prescribing viewed positively by nurses include continuity of care, increased satisfaction, and the belief that patients receive improved information about prescriptions. There is some evidence, however, that nurses feel ill-prepared to prescribe due to poor understanding of pharmacology, physical assessment and diagnosis. This paper reports a study assessing the extent to which independent extended supplementary nurse prescribers feel prepared to prescribe medicines for patients with dermatological conditions. A convenience sample of 1187 qualified independent extended supplementary nurse prescribers was sent a postal questionnaire. A total of 868 completed questionnaires was returned, and 638 of these nurses prescribed medicines for skin conditions. The data were collected in 2005. A total of 605 (94.8%) participants used independent extended prescribing and 234 (36.7%) supplementary prescribing. The majority were highly experienced and worked in primary care. In general, their prescribing programme had met their needs when prescribing medicines for patients with dermatological conditions. However, the needs of those who had undertaken a diploma-level module in dermatology and/or dermatology study days, and those working in both primary and secondary care, were met to a statistically significantly greater extent during the programme than for those nurses without this preparation, or those working in either primary or secondary care. Independent extended supplementary prescribing has extended the role that nurses in the United Kingdom are able to play in the management of skin disease. Specialist dermatology training is a prerequisite for nurses adopting this role. Further evaluative work on patient-focused outcomes, i.e. accessibility and convenience of care, and satisfaction with quality of care, is required.


A new species of Myxobolus (Myxozoa: Bivalvulida) infecting the medulla oblongata and nerve cord of brook trout Salvelinus fontinalis in southern Appalachia (New River, NC, USA).
Myxobolus neurofontinalis n. sp. infects the brain and medulla oblongata of brook trout (Salvelinus fontinalis [Mitchill, 1814]) in the New River, western NC. It is the first species of Myxobolus described from the brook trout and resembles another congener (Myxobolus arcticus Pugachev and Khokhlov, 1979) that infects nerve tissue of chars (Salvelinus spp.). The new species differs from M. arcticus and all congeners by myxospore dimensions and by having a mucous envelope and distinctive sutural markings. A phylogenetic analysis of the small subunit rDNA (18S) suggests that the new species shares a recent common ancestor with some isolates identified as M. arcticus and that the new species and its close relatives (except Myxobolus insidiosus Wyatt and Pratt, 1973) comprise a clade of salmonid nerve-infecting myxobolids. The phylogenetic analysis indicates that several isolates of "M. arcticus" (sensu lato) in GenBank are misidentified and distantly related to other isolates taken from the type host (Oncorhynchus nerka [Walbaum, 1792]) and from nearby the type locality (Kamchatka Peninsula, Russia). Serial histological sections of infected brook trout confirmed that myxospores of the new species are intercellular and infect nerve cord and medulla oblongata only. A single infected brook trout showed an inflammatory response characterized by focal lymphocytic infiltrates and eosinophilic granulocytes; however, the remaining 4 brook trout lacked evidence of a histopathological change or demonstrable host response. These results do not support the notion that this infection is pathogenic among brook trout.


Functional and proteomic analysis of serum and cerebrospinal fluid derived from patients with traumatic brain injury: a pilot study.
An enhanced fracture healing response has been reported in patients with traumatic brain injury (TBI). This has been attributed to circulating humoral factors that are thought to be proteins produced and released by the injured brain. However, these factors remain unknown. The aim of this study was to identify osteogenic factors in serum and cerebrospinal fluid (CSF) from TBI patients. This was carried out using in vitro proliferation assays with the human foetal osteoblastic 1.19 cell line (hFOB) combined with a novel proteomic approach. Serum was collected from brain-injured (n = 12) and non-brain-injured (n = 9) patients with a comorbid femur shaft fracture. Similarly, CSF was obtained from TBI (n = 7) and non-TBI (n = 9) patients. The osteoinductive potential of these samples was determined by measuring the in vitro proliferation rate of hFOB cells. Highly osteogenic serum and CSF samples of TBI patients were chosen for protein analysis and were compared to those of non-brain-injured patients. A new hFOB cell-based method was used to enrich the proteins in these samples, which had a functional affinity for these osteoprogenitor cells. These enriched protein fractions were mapped using two-dimensional gel electrophoresis and protein imaging methods displaying serum and CSF proteins of brain-injured and control subjects that had an affinity for human osteoprogenitor cells. Serum and CSF derived from brain-injured patients demonstrated a greater osteoinductive potential (P < 0.05) than their non-brain-injured counterparts. Clear-cut differences in the pattern of proteins in two-dimensional gels were detected between TBI and control patients. Fourteen proteins were exclusively present in the serum of TBI patients, while other proteins were either up- or downregulated in samples collected from TBI patients (P < 0.05). Osteoinductive factors are present in the serum and CSF of brain-injured patients. These may include one or more of those proteins identified as having an affinity for osteoprogenitor cells that are either exclusively present or up- or downregulated in the serum and CSF of brain-injured patients.


Fatigue is not associated with vitamin D deficiency in inflammatory bowel disease patients.
To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease (IBD). IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire (FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance. In total, 405 patients were included in the analyses, of which 227 (56%) had Crohn's disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency (< 50 nmol/L) was present in half (203/405) of the patients. Chronic fatigue was reported by 116 (29%) of all included patients with substantial fatigue reported by 194 (48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients. In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed.


Targeting glucose-dependent insulinotropic polypeptide receptor for neurodegenerative disorders.
Incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) exert pleiotropic effects on endocrine pancreas and nervous system. Expression of GIP and GIP receptor (GIPR) in neurons, their roles in neurogenesis, synaptic plasticity, neurotransmission, and neuromodulation uniquely position GIPR for therapeutic applications in neurodegenerative disorders. GIP analogs acting as GIPR agonists attenuate neurobehavioral and neuropathological sequelae of neurodegenerative disorders in preclinical models, e.g. Alzheimer's disease (AD), Parkinson's disease (PD), and cerebrovascular disorders. Modulation of GIPR signaling offers an unprecedented approach for disease modification by arresting neuronal viability decline, enabling neuronal regeneration, and reducing neuroinflammation. Growth-promoting effects of GIP signaling and broad-based neuroprotection highlight the therapeutic potential of GIPR agonists. Areas covered: This review focuses on the role of GIPR-mediated signaling in the central nervous system in neurophysiological and neuropathological conditions. In context of neurodegeneration, the article summarizes potential of targeting GIPR signaling for neurodegenerative conditions such as AD, PD, traumatic brain injury, and cerebrovascular disorders. Expert opinion: GIPR represents a validated therapeutic target for neurodegenerative disorders. GIPR agonists impart symptomatic improvements, slowed neurodegeneration, and enhanced neuronal regenerative capacity in preclinical models. Modulation of GIPR signaling is potentially a viable therapeutic approach for disease modification in neurodegenerative disorders.


Metabolic rate and clothing insulation data of children and adolescents during various school activities.
Data on metabolic rates (n = 81) and clothing insulation (n = 96) of school children and adolescents (A, primary school: age 9-10; B, primary school: age 10-11 year; C, junior vocational (technical) education: age 13-16 (lower level); D, same as C but at advanced level; and E, senior vocational (technical) education, advanced level: age 16-18) were collected (Diaferometer, Oxylog, Heart Rate derivation) during theory-, practical- and physical education- lessons. Clothing insulation was calculated from clothing weight, covered body surface area, and the number of clothing layers worn. Clothing insulation was found to be similar to that expected for adults in the same (winter) season, with minimal variation with age or school type (0.9 to 1.0 clo; 1.38 clo where coverall was worn), but more variation within groups (coefficient of variation 6-12%). Metabolic rate values (W.m(-2)) were lower than expected from adult data for similar activities, but are supported by other child data. The results of this study can be used to establish design criteria for school climate control systems or as general data on energy expenditure for children and adolescents. The results emphasize the need for specific child data and show the limited value of size-corrected adult data for use in children.


The challenges and innovations for therapy in children with epilepsy.
Major advances have been made in the diagnosis, evaluation and management of children with epilepsy over the past 15 years. There has been a marked increase in genetic diagnoses of a number of key childhood-onset epilepsy syndromes, such as Dravet syndrome, which has been linked to mutations in the SCN1A gene. The reorganization and reclassification of epilepsies, devised by the International League Against Epilepsy, has stimulated specialists to reassess their diagnostic practices; however, many studies have not addressed the global issues in treating children with epilepsy-specifically, the challenges of diagnosis through to optimal, and appropriate, therapeutic management. Also, Class I evidence-based data that are needed as a foundation for the development of treatment guidelines worldwide are lacking. Epilepsy is common, and the impact of this disease crosses age ranges and should be managed at all levels of care from community to quaternary care. In this Review, existing data and new therapeutic management approaches are discussed with the aim of highlighting the incidence of standard practices that may not be based on clinical evidence.


Analyses of the Complete Genome Sequence of the Strain Bacillus pumilus ZB201701 Isolated from Rhizosphere Soil of Maize under Drought and Salt Stress.
Bacillus pumilus ZB201701 is a rhizobacterium with the potential to promote plant growth and tolerance to drought and salinity stress. We herein present the complete genome sequence of the Gram-positive bacterium B. pumilus ZB201701, which consists of a linear chromosome with 3,640,542 base pairs, 3,608 protein-coding sequences, 24 ribosomal RNAs, and 80 transfer RNAs. Genome analyses using bioinformatics revealed some of the putative gene clusters involved in defense mechanisms. In addition, activity analyses of the strain under salt and simulated drought stress suggested its potential tolerance to abiotic stress. Plant growth-promoting bacteria-based experiments indicated that the strain promotes the salt tolerance of maize. The complete genome of B. pumilus ZB201701 provides valuable insights into rhizobacteria-mediated salt and drought tolerance and rhizobacteria-based solutions for abiotic stress in agriculture.


Programmable broadband radio-frequency transversal filter with compact fiber-optics and digital microelectromechanical system-based optical spectral control.
To the best of our knowledge, for the first time a programmable broadband rf transversal filter is proposed that operates on the principle of broadband optical spectral control implemented with a spatial light modulator input rf signal time delay and weight selection over a near-continuous signal space. Specifically, the filter uses a chirped fiber Bragg grating in combination with a two-dimensional digital micromirror device to enable a programmable rf filter. As a first step, a two-tap rf notch filter is demonstrated with a tuning range of 0.563-6.032 GHz with a 25-dB notch depth at test notch frequencies of 845 and 905 MHz. The proposed filter can find applications in diverse fields such as radar, communications, medicine, and test and measurement.


Anticipation of tennis-shot direction from whole-body movement: the role of movement amplitude and dynamics.
While recent studies indicate that observers are able to use dynamic information to anticipate whole-body actions like tennis shots, it is less clear whether the action's amplitude may also allow for anticipation. We therefore examined the role of movement dynamics and amplitude for the anticipation of tennis-shot direction. In a previous study, movement dynamics and amplitude were separated from the kinematics of tennis players' forehand groundstrokes. In the present study, these were manipulated and tennis shots were simulated. Three conditions were created in which shot-direction differences were either preserved or removed: Dynamics-Present-Amplitude-Present (D(P)A(P)), Dynamics-Present-Amplitude-Absent (D(P)A(A)), and Dynamics-Absent-Amplitude-Present (D(A)A(P)). Nineteen low-skill and 15 intermediate-skill tennis players watched the simulated shots and predicted shot direction from movements prior to ball-racket contact only. Percent of correctly predicted shots per condition was measured. On average, both groups' performance was superior when the dynamics were present (the D(P)A(P) and D(P)A(A) conditions) compared to when it was absent (the D(A)A(P) condition). However, the intermediate-skill players performed above chance independent of amplitude differences in shots (i.e., both the D(P)A(P) and D(P)A(A) conditions), whereas the low-skill group only performed above chance when amplitude differences were absent (the D(P)A(A) condition). These results suggest that the movement's dynamics but not their amplitude provides information from which tennis-shot direction can be anticipated. Furthermore, the successful extraction of dynamical information may be hampered by amplitude differences in a skill-dependent manner.


Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects.
According to the WHO-EORTC classification of cutaneous lymphomas, primary cutaneous marginal zone B-cell lymphoma are now well characterized. We report here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old man in which the diagnosis was made using both histology and immunopathology. The patient had no remarkable medical history, no history of either acute inflammation or insect bite, and presented with a 5 cm solitary asymptomatic erythematous firm, multinodular and infiltrated plaque on the back for 12 months. Histological examination and immunohistochemical study of a cutaneous biopsy provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis. Full body work up revealed no signs of extracutaneous dissemination. The patient underwent surgical excision of the nodule. Histological examination showed a histological and immunophenotyping profile typical of primary cutaneous marginal zone B-cell lymphoma. The lesion was completely excised with clear margins and no recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a high tendency to recur. They should be differentiated from lymphocytoma cutis and from the other types of cutaneous B cell lymphomas that have a different course and prognosis.


Complete remission of childhood-onset epilepsy: stability and prediction over two decades.
The ultimate seizure outcome of childhood epilepsy is complete resolution of all seizures without further treatment. How often this happens and how well it can be predicted early in the course of epilepsy could be valuable in helping families understand the nature of childhood epilepsy and what to expect over time. In the Connecticut study of epilepsy, a prospective cohort of 613 children with newly-diagnosed epilepsy (onset age 0-15 years), complete remission, ≥5 years both seizure-free and medication-free, was examined as a proxy of complete seizure resolution. Predictors at initial diagnosis were tested. Information about seizure outcomes within 2 years and from 2-5 years after diagnosis was sequentially added in a proportional hazards model. The predictive value of the models was determined with logistic regression. Five hundred and sixteen subjects were followed ≥10 years. Three hundred and twenty-eight (63%) achieved complete remission; 23 relapsed. The relapse rate was 8.2 per 1000 person-years and decreased over time: 10.7, 6.7, and 0 during first 5 years, the next 5 years, and then >10 years after complete remission (P=0.06 for trend). Six participants regained complete remission; 311 (60%) were in complete remission at last contact. Baseline factors predicting against complete remission at last contact included onset age≥10 years (hazard ratio=0.55, P=0.0009) and early school or developmental problems (hazard ratio=0.74, P=0.01). Factors predicting for complete remission were uncomplicated epilepsy presentation (hazard ratio=2.23, P<0.0001), focal self-limited epilepsy syndrome (hazard ratio=2.13, P<0.0001), and uncharacterized epilepsy (hazard ratio=1.61, P=0.04). Remission (hazard ratio=1.95, P<0.0001) and pharmaco-resistance (hazard ratio=0.33, P<0.0001) by 2 years respectfully predicted in favour and against complete remission. From 2 to 5 years after diagnosis, relapse (hazard ratio=0.21, P<0.0001) and late pharmaco-resistance (hazard ratio=0.21, P=0.008) decreased and late remission (hazard ratio=2.40, P<0.0001) increased chances of entering complete remission. The overall accuracy of the models increased from 72% (baseline information only), to 77% and 85% with addition of 2-year and 5-year outcomes. Relapses after complete remission are rare making this an acceptable proxy for complete seizure resolution. Complete remission after nearly 20 years is reasonably well predicted within 5 years of initial diagnosis.


Memory disorder in Korsakoff's psychosis: a neuropathological and neuropsychological investigation of two cases.
Neuropathological findings in the brains of two alcoholic patients with Korsakoff's psychosis are reported. Their memory defects had been studied in detail quantitatively over a period of nine years in one case and three years in the other, relevant details of which are presented. Both patients had had a relatively pure long-term memory impairment in the absence of other cognitive deficits and in the absence of a short-term memory impairment. Their retrograde amnesia for public events and famous faces had been measured and found to have extended backwards over at least twenty-five years. There was severe impairment in anterograde recognition memory for both verbal and non-verbal material. On a newly prepared memory quotient battery both patients had scored well below the bottom of the normal scale (less than 60, where 100 is the mean with a standard deviation of +/- 15). Both patients had also shown the characteristic differential improvement in retention when tested by cued recall and also the characteristic 'prior learning effect', i.e. normal retention of one list of words when tested by cued recall but impaired retention of a second list sharing the same cues as the first list. There had been a slight but significant deterioration in intelligence in one of the patients in the two years prior to his death, although his IQ still fell within the normal range. The other patient remained undeteriorated until his death, and his IQ also was close to an estimated measure of his premorbid IQ. In the brains of both patients there was marked gliosis, shrinkage and discolouration bilaterally in the medial nuclei of the mammillary bodies. In addition there was a thin band of gliosis bilaterally between the wall of the third ventricle and the medial dorsal nucleus, the rostral limit lying anterior to the medial dorsal nucleus. In the patient with no intellectual deterioration these were the only pathological changes that were seen. In neither patient was there evident local loss of nerve cells, gliosis or any other qualitative evidence of abnormality in the hippocampi, the white matter of the temporal lobes or the greater part of the medial dorsal nuclei, although it is difficult to be certain whether there was any overlap between the band of gliosis and the most medial region of the medial dorsal nueleus and other adjacent thalamic nuclei. In the other patient there was also a small zone of softening in the cerebellum and an increase in astrocytes in other regions of the cerebral hemispheres, including the basal ganglia, amygdala, and brain-stem, but without noticeable loss of cells. The question of the minimal lesion for the alcoholic Korsakoff amnesic state, and some aspects of the related anatomy, is discussed in the context of other reports in the literature which are, however, difficult to assess in the absence of details of the specificity, severity and character of the memory disorders.


The acoustical characteristics of the normal temporomandibular joint.
Both clinical and empirical evidence suggests that the "normal" temporomandibular joint produces noise during function. The purpose of this study was to determine the conditions under which these noises might arise. Joint sounds and mandibular movements were recorded simultaneously from 200 adults who had no previous history or present symptoms of TMJ pain or dysfunction. The joint sounds were recorded bilaterally by means of two separate miniature vibration transducers mounted on a common headband, and incisal point mandibular movements were measured by a magnetometer tracking system. Recordings were made while each subject opened and closed the mouth, first in a natural and comfortable manner, and then to maximum displacement. Two types of measurements were made: the appearance, onset, and duration of joint-propagated sounds in relation to relative mandibular position; and the spectral properties of the detected sounds. The results of this study showed that for natural opening and closing movements of the mandible, the "normal" TMJ was silent for all age groups. However, for the maximum displacement condition, detectable sounds appeared at the points of maximum displacement in both the opening and closing phases of the cycle in over 80 percent of the subjects. However, these sounds were, as a class, substantially longer than, and spectrally distinct from, abnormal joint sounds, suggesting that they arise from a distinct physical substrate.


Cardioembolic Stroke Risk and Recovery After Anticoagulation-Related Intracerebral Hemorrhage.
Background and Purpose- Whether to resume oral anticoagulation treatment after intracerebral hemorrhage (ICH) remains an unresolved question. Previous studies focused primarily on recurrent stroke after ICH. We sought to investigate the association between cardioembolic stroke risk, oral anticoagulation therapy resumption, and functional recovery among ICH survivors in the absence of recurrent stroke. Methods- We conducted a joint analysis of 3 observational studies: (1) the multicenter RETRACE study (German-Wide Multicenter Analysis of Oral Anticoagulation Associated Intracerebral Hemorrhage); (2) the Massachusetts General Hospital ICH study (n=166); and (3) the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage; n=131). We included 941 survivors of ICH in the setting of active oral anticoagulation therapy for prevention of cardioembolic stroke because of nonvalvular atrial fibrillation and without evidence of ischemic stroke and recurrent ICH at 1 year from the index event. We created univariable and multivariable models to explore associations between cardioembolic stroke risk (based on CHA2DS2-VASc scores) and functional recovery after ICH, defined as achieving modified Rankin Scale score of ≤3 at 1 year for participants with modified Rankin Scale score of >3 at discharge. Results- In multivariable analyses, the CHA2DS2-VASc score was associated with a decreased likelihood of functional recovery (odds ratio, 0.83 per 1 point increase; 95% CI, 0.79-0.86) at 1 year. Anticoagulation resumption was independently associated with a higher likelihood of recovery, regardless of CHA2DS2-VASc score (odds ratio, 1.89; 95% CI, 1.32-2.70). We found an interaction between CHA2DS2-VASc score and anticoagulation resumption in terms of association with increased likelihood of functional recovery (interaction P=0.011). Conclusions- Increasing cardioembolic stroke risk is associated with a decreased likelihood of functional recovery at 1 year after ICH, but this association was weaker among participants resuming oral anticoagulation therapy. These findings support, including recovery metrics, in future studies of anticoagulation resumption after ICH.


Pain and Menopause Symptoms of Breast Cancer Patients with Adjuvant Hormonal Therapy in Korea: Secondary Analysis.
The purpose of this study was to describe the prevalence and levels of pain and menopause symptoms of breast cancer patients with adjuvant hormonal therapy (HT). A cross-sectional survey design was used. Secondary analysis was used from the primary data collected in 2013 from a total of 110 breast cancer patients receiving HT for more than 3 months, using questionnaires of the Korean version of brief pain inventory and the menopause rating scale. Mean age of the participants was 53.56. Most (88.2%) of the participants reported to have pain and almost (95.5%) of them reported to have menopause symptoms. More pain was reported in participants with aromatase inhibitor (AI) than those with tamoxifen. Adherence to HT showed a significant difference according to the rate of feeling increased pain (P = 0.001). Among the menopause symptoms, fatigue was the most common symptom (97.3%). Sweating/flush was significantly higher in tamoxifen group (P < 0.005), and joint and muscle complaints were higher in AI group (P < 005). The results of the study show that the prevalence and levels of pain and menopause symptoms among breast cancer patients receiving HT were high. Thus, oncology professionals need to provide appropriate interventions to relieve pain and menopause symptom to improve adherence to HT.


Potential CO2 leakage reduction through biofilm-induced calcium carbonate precipitation.
Mitigation strategies for sealing high permeability regions in cap rocks, such as fractures or improperly abandoned wells, are important considerations in the long term security of geologically stored carbon dioxide (CO(2)). Sealing technologies using low-viscosity fluids are advantageous in this context since they potentially reduce the necessary injection pressures and increase the radius of influence around injection wells. Using aqueous solutions and suspensions that can effectively promote microbially induced mineral precipitation is one such technology. Here we describe a strategy to homogenously distribute biofilm-induced calcium carbonate (CaCO(3)) precipitates in a 61 cm long sand-filled column and to seal a hydraulically fractured, 74 cm diameter Boyles Sandstone core. Sporosarcina pasteurii biofilms were established and an injection strategy developed to optimize CaCO(3) precipitation induced via microbial urea hydrolysis. Over the duration of the experiments, permeability decreased between 2 and 4 orders of magnitude in sand column and fractured core experiments, respectively. Additionally, after fracture sealing, the sandstone core withstood three times higher well bore pressure than during the initial fracturing event, which occurred prior to biofilm-induced CaCO(3) mineralization. These studies suggest biofilm-induced CaCO(3) precipitation technologies may potentially seal and strengthen fractures to mitigate CO(2) leakage potential.


The pathogenesis of dermatophilosis.
Pathogen, host and environmental factors must be considered in order to understand the pathogenesis of dermatophilosis. A frequently cited sequence of events involves physical damage to the skin, bacterial multiplication in the epidermis, repeated cycles of invasion by hyphae, infiltration by neutrophils and exudate, regeneration of epidermis and reinvasion. This paper is concerned with pathogen driven mechanisms involved in the origin and development of Dermatophilus congolensis infections. Primary infections of calves under controlled conditions at clipped, cleaned, defatted sites result in characteristic dermatophilosis crusts, illustrating that D. congolensis itself is pathogenic. Calves infected in this way develop protective immune responses to subsequent infections. In contrast first and second infections of calves simultaneously infested with Amblyomma variegatum result in more severe lesions that take significantly longer to heal than lesions on tick free calves. Immunity to D. congolensis is isolate specific, however the antigens that elicit immunity have not been defined, they might include pathogenic or virulence factors. Hyphae are the life-cycle stage most closely associated with the living epidermis. During in vitro growth hyphae secrete antigens and proteolytic enzymes into culture medium. Proteolytic activity has been linked to virulence of D. congolensis. The characteristics of proteases released into culture medium varies between isolates. This raises the possibility that proteases, with as yet undefined functions, act as pathogenic and virulence factors, that they are the targets for protective immune responses and that A. variegatum infestation interferes with host immune responses that normally inhibit their activity.


Discontinuation of antipsychotic medication in pregnancy: a cohort study.
Women prescribed antipsychotics face the dilemma on whether to continue medication in pregnancy in terms of balancing risks and benefits. Previous research on other psychotropic medications suggests that many women discontinue treatment in early pregnancy. However, very limited evidence exists on discontinuation of antipsychotic medication. We identified 495,953 pregnant women from THIN primary care database. Kaplan-Meier plots were used to examine time to last antipsychotic prescription. Poisson regression was used to examine characteristics of those who stopped treatment during pregnancy. There has been an overall increase in prevalence of antipsychotic prescribing since 2007. However, antipsychotics were more likely to be stopped in pregnant than non-pregnant women. Only 107/279 (38%) of women on atypical antipsychotics and 39/207 (19%) of women on typical antipsychotics before pregnancy still received treatment at the start of third trimester. Older women were more likely to continue typical antipsychotic treatment in pregnancy (35+ versus <25 years risk ratio: 3.09 [95% CI 1.76, 5.44]). Likewise, those who received typical antipsychotics for longer periods before were most likely to continue treatment in pregnancy (12+ versus <6 months: RR: 3.12 [95% CI 1.97, 4.95]). For atypical antipsychotics length and dose of prior prescribing were also associated with continuation in pregnancy. Pregnancy was a major determinant of cessation of antipsychotics. Only 38% of women on atypical and 19% on typical antipsychotics were still prescribed the drug in the third trimester. Duration of prior treatment, maternal age as well as dose was significantly associated with continued treatment of antipsychotics in pregnancy.


Cognitive biases in the peer review of bullet and cartridge case comparison casework: A field study.
Forensic judgments and their peer review are often the result of human assessment and are thus subjective and prone to bias. This study examined whether bias affects forensic peer review. We hypothesized that the probability of disagreement between two forensic examiners about the proposed conclusion would be higher with "blind" peer review (reviewer saw only the first examiner's comparison photos) than with "non-blind" peer review (reviewer also saw the first examiner's interpretation and proposed conclusion). We also hypothesized that examiners with a higher perceived professional status would have a larger effect on the reported conclusion than examiners with a lower status. We acquired data during a non-blind and a blind peer review procedure in a naturalistic, covert study with eight examiners (3-26 years of experience). We acquired 97 conclusions of bullet and cartridge case comparisons in the blind and 471 in the non-blind peer review procedure. The odds of disagreement between examiners about the evidential strength of a comparison were approximately five times larger (95%-CI [3.06, 8.50]) in the blind than in the non-blind procedure, with disagreement about 42.3% and 12.5% of the proposed conclusions, respectively. Also, the odds that their proposed conclusion was reported as the final conclusion were approximately 2.5 higher for the higher-status examiners than for lower-status examiners. Our results support both the hypothesis that bias occurs during non-blind forensic peer review and the hypothesis that higher-status examiners determine the outcome of a discussion more than lower-status examiners. We conclude that blind peer review may reduce the probability of bias and that status effects have an impact on the peer reviewing process.


The aging gender dysphoria (transsexual) patient.
Ten aging gender dysphoria patients (eight men and two women, average age 52 years) were the subjects of this study. All had presented to the Gender Identity Clinic at Case Western Reserve University requesting sex-reassignment surgery. A psychiatric-psychological profile of the patients, their sexual functioning, problems with aging, diagnostic issues, and follow-up are discussed. The aging gender dysphoric patient presents in acute crisis, that is, exhibiting marked depression, increased suicidal ideation and behavior, and urgent perception of time. Diagnostic and treatment recommendations for aging gender dysphoria patients and their depressions are provided. Furthermore, guidelines are suggested for differentiating the aging transvestite with transsexual symptoms and the aging transsexual for whom sex-reassignment surgery may be indicated. Specific treatment strategies for an aging population, including sexual surgery, are also discussed.


Minimally invasive mitral surgery through right mini-thoracotomy under direct vision.
In the 1990s, the success of 'minimally invasive' laparoscopic operations in other surgical subspecialties sparked an interest in minimally-invasive approaches for cardiac surgery, specifically for mitral valve repair. In 1996 at New York University (NYU) we began our experience with minimally invasive mitral valve repair performed through a small right anterior mini-thoracotomy incision using the Port-Access system in a phase I clinical trial. This was the beginning of our extensive right mini-thoracotomy experience for mitral valve repair at NYU. Currently at our institution the preferred approach for the right mini-thoracotomy mitral valve surgery is through the 3rd or 4th interspace mini-thoracotomy incision. Perfusion is accomplished with direct aortic or femoral cannulation, long femoral venous cannula drainage, and a retrograde cardioplegia catheter placed trans-atrialy in the coronary sinus under TEE guidance. An antegrade cardioplegia and venting needle is placed in the ascending aorta and direct external aortic clamping is achieved with one of several specialized crossclamps. With over four decades of experience, more than 4,000 patients have undergone mitral valve repair at NYU including 1,922 performed through a right mini-thoracotomy. We have reported an overall operative mortality of 1.3%, 8-year freedom from reoperation of 95%, freedom from reoperation or severe recurrent mitral regurgitation of 93%, and freedom from all valve-related complications of 90% for our initial series of 1,071 right mini-thoracotomy mitral valve repair. Based on our extensive experience we believe that mitral valve repair through a right mini-thoracotomy provides a durable and safe alternative to a traditional sternotomy with the benefits of improved cosmesis, reduced post-operative pain, less blood loss with fewer blood transfusions, fewer infections, shorter length of stay, and faster return to activity. It is our standard of care approach for mitral valve surgery.


The effects of intravenous nitroglycerine and norepinephrine on gastric microvascular perfusion in an experimental model of gastric tube reconstruction.
Esophagectomy with gastric tube reconstruction is the surgical treatment for cancer of the esophagus. Perfusion of the anastomotic site of the tube depends exclusively on microcirculation, making it susceptible to hypoperfusion. It is unknown whether vasodilatation is superior to increased perfusion pressure to improve gastric tissue perfusion of the anastomosis. We performed a gastric tube reconstruction in 12 pigs, mean body weight 32 +/- 2 kg. Besides systemic hemodynamic parameters, gastric microvascular blood flow (MBF) was assessed with laser Doppler flowmetry and gastric microvascular HbO(2) saturation (microHbSO(2)) and Hb concentration (microHbcon) with spectrophotometry. Animals were randomized over 2 groups: with and without intravenous nitroglycerin (NTG). In both groups, mean arterial pressure (MAP) was increased from 50 to 110 mmHg with infusion of norepinephrine; in the NTG group, central venous pressure was maintained below 10 mmHg throughout the experiment with NTG. Except for central venous and pulmonary capillary wedge pressures, all hemodynamic parameters were similar in both groups. Especially in corpus and fundus, MBF decreased following surgery. However, overall MBF was significantly higher in the NTG group. Increasing MAP had no effect on fundus MBF. Gastric microHbSO(2) and microHbcon were not different between groups and did not change at higher MAP levels. In our experimental model of gastric tube reconstruction, tissue perfusion is severely compromised; this effect is aggravated by systemic hypotension independent from cardiac output. Impaired venous outflow might contribute to this effect and can be counteracted with infusion of nitroglycerine.


The expression of androgen receptor in neurons of the anterior pelvic ganglion and celiac-superior mesenteric ganglion in the male pig.
The present study investigated the expression of androgen receptor (AR) in neurons of the anterior pelvic ganglion (APG) and celiac-superior mesenteric ganglion (CSMG; ganglion not involved in the innervation of reproductive organs) in the male pig with quantitative real-time PCR (qPCR) and immunohistochemistry. qPCR investigations revealed that the level of AR gene expression in the APG tissue was approximately 2.5 times higher in the adult (180-day-old) than in the juvenile (7-day-old) boars. Furthermore, in both the adult and juvenile animals it was sig- nificantly higher in the APG than in CSMG tissue (42 and 85 times higher, respectively). Immu- nofluorescence results fully confirmed those obtained with qPCR. In the adult boars, nearly all adrenergic (DβH-positive) and the majority of non-adrenergic neurons in APG stained for AR. In the juvenile animals, about half of the adrenergic and non-adrenergic neurons were AR-posi- tive. In both the adult and juvenile animals, only solitary CSMG neurons stained for AR. The present results suggest that in the male pig, pelvic neurons should be considered as an element of highly testosterone-dependent autonomic circuits involved in the regulation of urogenital func- tion, and that their sensitization to androgens is a dynamic process, increasing during the prepu- bertal period.


Intra-operative ultrasound elasticity imaging for monitoring of hepatic tumour thermal ablation.
Thermal ablation is an accepted therapy for selected hepatic malignancies. However, the reliability of thermal ablation is limited by the inability to accurately monitor and confirm completeness of tumour destruction in real time. We investigated the ability of ultrasound elasticity imaging (USEI) to monitor thermal ablation. Capitalizing on the known increased stiffness that occurs with protein denaturation and dehydration during thermal therapy, we sought to investigate the feasibility and accuracy of USEI for monitoring of liver tumour ablation. A model for hepatic tumours was developed and elasticity images of liver ablation were acquired in in vivo animal studies, comparing the elasticity images to gross specimens. A clinical pilot study was conducted using USEI in nine patients undergoing open radiofrequency ablation for hepatic malignancies. The size and shape of thermal lesions on USEI were compared to B-mode ultrasound and post-ablation computed tomography (CT). In both in vivo animal studies and in the clinical trial, the boundary of thermal lesions was significantly more conspicuous on USEI when compared with B-mode imaging. Animal studies demonstrated good correlation between the diameter of ablated lesions on USEI and the gross specimen (r = 0.81). Moreover, high-quality strain images were generated in real time during therapy. In patients undergoing tumour ablation, a good size correlation was observed between USEI and post-operative CT (r = 0.80). USEI can be a valuable tool for the accurate monitoring and real-time verification of successful thermal ablation of liver tumours.


Long-term marine litter monitoring in the remote Great Australian Bight, South Australia.
The Anxious Bay beach litter clearance is the longest running annual survey of ocean-based litter in Australia. It's remoteness from centres of human population and location (with respect to prevailing winds and currents) make it an ideal place for monitoring ocean or ship-based litter in Australia's southern oceans and particularly, the Great Australian Bight. Over the 1991-1999 period, a large but gradual decline in the amount of beach washed litter was recorded (with minor peaks recorded during the 1992 and 1994 surveys). Beach washed litter decreased by approximately 86%, from 344 kg recorded in 1991 (13.2 kg/km) to 49 kg in 1999 (i.e. 1.9 kg/km), reaching a maximum of 390 kg in 1992 (or 15 kg/km of beach). However, a sharp increase in litter was recorded in 2000 (i.e. 252 kg or 9.7 kg/km). This increase in litter yield in 2000 is probably due to stronger than average onshore surface flow (or Ekman Transport) in the western Eyre Peninsula and Bight region. Prior to the survey in 2000, the results appeared to indicate that ocean litter on Anxious Bay beach was beginning to level out at around 50-70 kg/year (i.e. 2-3 kg/km). As the beach surveys involve the assumption that the beach is completely cleared of litter, this may represent a baseline level for ocean-based litter in the region. The yields and type of litter collected from the annual survey indicates that the majority of litter washed ashore originates from commercial fishing activities within the Great Australian Bight. Most of the fishing-related litter was directly sourced to the Southern Rock Lobster Fishery (i.e. bait buckets, baskets, pots), the Great Australian Bight Trawl Fishery (i.e. codends, trawl nets) and the Southern Shark Fishery (i.e. monofilament gillnets and longlines). Between 1994 and 1999, large reductions were observed in the amount of bait straps (77% reduction), lobster bait baskets/buckets (86% reduction), nets/ropes (62% reduction) and floats/buoys (83% reduction). Significantly, fishing-related litter in the Bight has reduced at a slower rate than domestic litter. While the level of glass and soft plastics on the beach have both reduced by almost 93% (i.e. 103-7 kg and 119-8 kg, respectively), the level of hard plastics, has diminished at a slower rate, with reductions of only 75% (i.e. 122-30 kg). Some fisheries (i.e. rock lobster, Southern Shark Fishery) have shown marked reductions in fishing-related litter. This is probably due, to some extent, to significant reductions in fishing effort in the region, although this requires further investigation. The information from the Anxious Bay beach litter survey is crucial in monitoring trends in ocean litter in Australia's southern oceans and compliance with international litter regulations. While fishing-related litter remains the major source of ship-based or ocean litter in Australia's southern oceans, the continued reduction in ship-based litter since 1991 supports increasing compliance to MARPOL (Annex V) by commercial fisheries and shipping in the Great Australian Bight. While Australia participates in marine debris monitoring programs in the Antarctic (under CCAMLR), there is currently no national program or management framework to assess, manage and monitor ocean-based litter along Australia's coasts, and monitor compliance with MARPOL. Apart from the commitments under CCAMLR for Antarctic (and sub-Antarctic) marine environments, there are no other regional programs, guidelines or monitoring protocols or to assess and manage ocean litter in the Southern Ocean.


Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology.
Placebo response theory and set and setting theory are two fields which examine how non-biological factors shape the response to therapy. Both consider factors such as expectancy, preparation and beliefs to be crucial for understanding the extra-pharmacological processes which shape the response to drugs. Yet there are also fundamental differences between the two theories. Set and setting concerns itself with response to psychoactive drugs only; placebo theory relates to all therapeutic interventions. Placebo theory is aimed at medical professionals; set and setting theory is aimed at professionals and drug users alike. Placebo theory is primarily descriptive, describing how placebo acts; set and setting theory is primarily prescriptive, educating therapists and users on how to control and optimize the effects of drugs. This paper examines how placebo theory and set and setting theory can complement and benefit each other, broadening our understanding of how non-biological factors shape response to drugs and other treatment interventions.


A subcortical network of dysfunction in TLE measured by magnetic resonance spectroscopy.
The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using (1)H magnetic resonance spectroscopic imaging. (1)H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures.


The computational analysis of human testis transcriptome reveals closer ties to pluripotency.
The purpose of this study was to identify the differentially expressed genes (DEG) in human testis and also evaluate the relationship between human testis, human Embryonic Stem Cells (hESC), mouse testis and mouse ESCs (mESC). It is a prospective analysis designed computationally. The microarray data for human testis, hESCs, mouse testis and mESCs were obtained from NCBI-GEO and analyzed for identification of DEGs. The results were then compared with mouse testis and extended to ESCs. Data was analyzed in R using various Bioconductor packages. To identify DEGs, 2-fold cut-off and a False Discovery Rate (FDR) below 0.01 criterions was used. A total 2868 transcripts (DEGs) were found to be significantly up-regulated and 2011 transcripts significantly down-regulated in human testis compared to other normal tissues. Of the up-regulated transcripts, 232 transcripts were grouped as unclassified i.e. had unknown annotations at the time of analysis. Gene Ontology (GO) based functional annotation of testis specific DEGs indicate that most of the DEGs (~80%) are involved in various metabolic processes. Pathway analysis shows over-representation of Ubiquitin-mediated proteolysis pathway. A core group of 67 transcripts were found to be common among human testis, mouse testis, hESCs and mESCs. Testis seems to be metabolically very active relative to other normal tissues as indicated by functional annotation. The comparison of human and mouse testis shows conserved functions and pathways involved in both species. Large numbers of genes were found conserved between testis and ESCs suggesting very close expression level relationship between reproductive organs and complex phenomenon such as dedifferentiation and reprogramming.


Molecular dynamics simulations of solvent-exfoliation and stabilization of graphene with the assistance of compressed carbon dioxide and pyrene-polyethylene glycol.
In this work we carried out molecular dynamics (MD) simulations to explore the mechanism of solvent-exfoliation and stabilization of graphene in the presence of (compressed) carbon dioxide (cpCO2), p-xylene and pyrene-polyethylene glycol (Py-PEG) polymers. We studied the role of each component in graphene exfoliation and stabilization by setting different experimental variables. The simulation results show that the cpCO2 molecules played a "wedge" role in the exfoliation process, firstly wedging into the interlayer, and then helping solvent molecules to insert into the interlayer. The solvent molecules between the graphene sheets are the main reasons that graphene exfoliation is achieved. And the Py-PEG polymer chains mainly act as stabilizers to prevent the exfoliated graphene sheets from restacking. This work provides detailed theoretical clues to better understand the mechanism of exfoliation and stabilization of graphene.


Current Trends and Healthcare Resource Usage in the Hospital Treatment of Primary Malignant Brain Tumor in Japan: A National Survey Using the Diagnostic Procedure Combination Database (J-ASPECT Study-Brain Tumor).
We conducted this study to clarify the current trends and healthcare resource usage in the treatment of inpatients with primary malignant brain tumors. The Diagnostic Procedure Combination (DPC) data of all inpatients treated between 2013 and 2014 in the 370 core and branch hospitals enrolled in the Japanese Neurosurgical Society training program were collected. DPC is a discharge abstract and administrative claims database of inpatients. We assessed 6,142 primary, malignant brain tumor patients. Patient information, diagnostic information, treatment procedure, and healthcare resource usage were analyzed. Chemotherapy was the most frequent treatment (27% of cases), followed by surgery (13%) and surgery + chemo-radiotherapy (11%). Temozolomide (TMZ), the most frequently used chemotherapeutic drug, was administered to 1,236 patients. Concomitant TMZ and radiotherapy was administered to 816 patients, and was performed according to the Stupp regimen in many cases. The mean length of hospital stay (LOS) was 16 days, and the mean medical cost was 1,077,690 yen. The average medical cost of TMZ-only treatment was 1,138,620 yen whilst it was 4,424,300 yen in concomitant TMZ patients. The LOS was significantly shorter in high-volume than in low-volume hospitals, and the medical cost was higher in hospitals treating 21-50 patients compared to those treating 1-10 patients. However, the direct medical cost of TMZ treatment was the same across different volume hospitals. This is the first report of current trends and healthcare resource usage in the treatment of primary malignant brain tumor inpatients in the TMZ era in Japan.


The utility of keg registration laws: a cross-sectional study.
Many states have implemented keg registration policies to reduce adolescent binge drinking and related consequences. We examined the association between the strength and comprehensiveness of these policies and measures of beer consumption in the general population and adolescent binge drinking, as well as drinking and driving. Data concerning the presence and stringency of the states' keg registration laws were secured from the Alcohol Policy Information System. Keg law ratings for each state were correlated with its (1) beer consumption per capita, as well as the 30-day prevalence of the following: (2) adolescent binge drinking, (3) adolescents who drive after drinking, and (4) adolescents who ride with a driver who has been drinking, as assessed by the Youth Risk Behavior Survey. As hypothesized, the stringency and comprehensiveness of state level keg registration laws were moderately (-.31 to -.41) and negatively associated with each of these outcomes. However, these relationships largely attenuated when controlling for per capita beer sales. Longitudinal research is needed to examine the relationships between keg registration policies and levels of adolescent alcohol consumption, hazardous drinking, and driving after drinking.


Syllables in Sync Form a Link: Neural Phase-locking Reflects Word Knowledge during Language Learning.
Language is composed of small building blocks, which combine to form larger meaningful structures. To understand language, we must process, track, and concatenate these building blocks into larger linguistic units as speech unfolds over time. An influential idea is that phase-locking of neural oscillations across different levels of linguistic structure provides a mechanism for this process. Building on this framework, the goal of the current study was to determine whether neural phase-locking occurs more robustly to novel linguistic items that are successfully learned and encoded into memory, compared to items that are not learned. Participants listened to a continuous speech stream composed of repeating nonsense words while their EEG was recorded and then performed a recognition test on the component words. Neural phase-locking to individual words during the learning period strongly predicted the strength of subsequent word knowledge, suggesting that neural phase-locking indexes the subjective perception of specific linguistic items during real-time language learning. These findings support neural oscillatory models of language, demonstrating that words that are successfully perceived as functional units are tracked by oscillatory activity at the matching word rate. In contrast, words that are not learned are processed merely as a sequence of unrelated syllables and thus not tracked by corresponding word-rate oscillations.


Germline pathogenic variants in patients with early-onset neuroendocrine neoplasms.
Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.


Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na+-dependent Pi transporter (NaPi-2) in the rat proximal tubule.
Dietary phosphate (Pi) intake and parathyroid hormone (PTH) are essential regulators of proximal tubular (PT) Pi reabsorption; both factors are associated with adaptive changes in PT apical brush border membrane (BBM) Na/Pi-cotransport activity and specific transporter protein (NaPi-2) content. Urinary Pi excretion is also inversely correlated with luminal Ca2+ concentration ([Ca2+]) both in a PTH-dependent and -independent fashion. A cell-surface, Ca2+(/polyvalent cation)-sensing receptor (CaR) has been localized to the PT BBM with unknown function. To investigate whether PTH and/or dietary Pi intake could affect the distribution or the expression of the CaR, we evaluated their effects on rat kidney CaR and the NaPi-2 expression by Western blot analysis and immunofluorescence microscopy. A chronic high-Pi (1.2%) versus low-Pi (0.1%) diet and acute PTH (1-34) infusion significantly reduced the PT BBM expression of both NaPi-2 and CaR proteins. CaR-specific immunoreactivity in nephron segments other than the PT was not affected by PTH or Pi intake. These results suggest that reduced renal PT CaR expression by a high-Pi diet and by increased circulating PTH levels could contribute to the local control of PT handling of Ca2+ and Pi.


Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy.
Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPalpha, PPARgamma, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFalpha were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.


Antioxidant activities and protective effects of duck embryo peptides against H2O2-induced oxidative damage in HepG2 cells.
Previous work showed that peptides from duck eggs incubated for 15 D presented high total antioxidant activities. Here, this work explore the antioxidant activities of different segments, ZT1 (≤3 KD), ZT2 (≤10 KD), and ZT3 (≤30 KD), derived from duck embryo peptides and their protective effects against H2O2-induced oxidative damage in HepG2 cells. Peptides present no cytotoxicity to HepG2 cells. Moreover, ZT1 exhibits a higher ability to scavenge several radicals as well as stronger inhibition of H2O2-induced oxidative stress than ZT2 and ZT3. The activities of catalase and glutathione peroxidase as well as total superoxide dismutase increase in a concentration-dependent manner. Peptides are isolated from ZT1 and then subjected to LC-MS/MS to identify their sequences, followed by functional annotation, bioinformatics prediction, and hot-spot motif recognition. As a result, 413 potential functional peptides are identified, with some compounds exhibiting more than 1 function. This work will help for exploring bioactive substances in duck embryo eggs and enhance the utilization value of duck or other poultry eggs.


Noninferiority of glucose-6-phosphate dehydrogenase deficiency diagnosis by a point-of-care rapid test vs the laboratory fluorescent spot test demonstrated by copper inhibition in normal human red blood cells.
Tens of millions of patients diagnosed with vivax malaria cannot safely receive primaquine therapy against repeated attacks caused by activation of dormant liver stages called hypnozoites. Most of these patients lack access to screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency, a highly prevalent disorder causing serious acute hemolytic anemia with primaquine therapy. We optimized CuCl inhibition of G6PD in normal red blood cells (RBCs) to assess G6PD diagnostic technologies suited to point of care in the impoverished rural tropics. The most widely applied technology for G6PD screening-the fluorescent spot test (FST)-is impractical in that setting. We evaluated a new point-of-care G6PD screening kit (CareStart G6PD, CSG) against FST using graded CuCl treatments to simulate variable hemizygous states, and varying proportions of CuCl-treated RBC suspensions to simulate variable heterozygous states of G6PD deficiency. In experiments double-blinded to CuCl treatment, technicians reading FST and CSG test (n = 269) classified results as positive or negative for deficiency. At G6PD activity ≤40% of normal (n = 112), CSG test was not inferior to FST in detecting G6PD deficiency (P = 0.003), with 96% vs 90% (P = 0.19) sensitivity and 75% and 87% (P = 0.01) specificity, respectively. The CSG test costs less, requires no specialized equipment, laboratory skills, or cold chain for successful application, and performs as well as the FST standard of care for G6PD screening. Such a device may vastly expand access to primaquine therapy and aid in mitigating the very substantial burden of morbidity and mortality imposed by the hypnozoite reservoir of vivax malaria.


Strong antibacterial properties of anion transporters: a result of depolarization and weakening of the bacterial membrane.
The development of low molecular weight anionophores is an emerging topic in chemistry, as the need for these compounds increases with the continuous discovery of pathologies involving anomalies in anion transport processes. Development of new concepts to initiate anion imbalance in living cells while fighting multidrug-resistant bacteria is a paramount topic. In this study, three series of compounds including N,N'-diphenylethynylbenzyl benzimidazolium salts (1 and 2), 1,1'-(pyridine-2,6-diyl)bis(3-(4-(phenylethynyl)benzyl)-1H-benzo[d]imidazol-3-ium) salts (3-5), and 1,1'-(pyridine-2,6-diylbis(methylene))bis(3-(4-(phenyl ethynyl)benzyl)-1H-benzo[d]imidazol-3-ium) salts (6-8) displaying high antimicrobial activity and low toxicity against human cells were designed, synthesized, and studied. The most potent compound displayed micromolar minimal inhibitory concentrations in different Gram-negative and Gram-positive bacteria, while its hemolytic activity remained around 10% or less, even after a prolonged period of exposure. The mechanism of action of these benzimidazolium salts on bacterial membrane was assessed by bioanalytical techniques including assays in model membrane liposomes, membrane depolarization studies, and scanning electron microscopy (SEM) in living bacteria.


Optogenetic control of PRC1 reveals its role in chromosome alignment on the spindle by overlap length-dependent forces.
During metaphase, chromosome position at the spindle equator is regulated by the forces exerted by kinetochore microtubules and polar ejection forces. However, the role of forces arising from mechanical coupling of sister kinetochore fibers with bridging fibers in chromosome alignment is unknown. Here, we develop an optogenetic approach for acute removal of PRC1 to partially disassemble bridging fibers and show that they promote chromosome alignment. Tracking of the plus-end protein EB3 revealed longer antiparallel overlaps of bridging microtubules upon PRC1 removal, which was accompanied by misaligned and lagging kinetochores. Kif4A/kinesin-4 and Kif18A/kinesin-8 were found within the bridging fiber and largely lost upon PRC1 removal, suggesting that these proteins regulate the overlap length of bridging microtubules. We propose that PRC1-mediated crosslinking of bridging microtubules and recruitment of kinesins to the bridging fiber promote chromosome alignment by overlap length-dependent forces transmitted to the associated kinetochore fibers.


Effect of cysteine peptidase inhibitor of Eudiplozoon nipponicum (Monogenea) on cytokine expression of macrophages in vitro.
The gills of the common carp, whose mucosal surface belongs to the key defence mechanisms of piscine immunity, can be infested with both the larval and adult stage of Eudiplozoon nipponicum (Monogenea). Although on their own, monogeneans do not considerably compromise their hosts' health status, fish with epithelial barriers damaged in parasite feeding and attachment sites are at an increased risk of bacterial challenge with possible harmful consequences. Several studies suggest that helminth parasites of teleost fish evade and manipulate host immune system via their excretory-secretory products, but our knowledge of these processes in the monogeneans is limited. Cysteine peptidase inhibitors (CPI), which are found in the secretions of numerous parasites, often induce immunosuppression by subverting Th1 mechanisms and drawing the immune system towards a Th2/Treg response. We employed the qPCR to test the effect of recently characterised CPI of E. nipponicum (rEnStef) on the mRNA expression of pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 produced by porcine macrophages in vitro. After an initial preincubation with rEnStef, we stimulated the macrophages using LPS. By inducing a Th1 pro-inflammatory response, we imitated the immune reaction during a bacterial challenge in tissue damaged by the feeding and attachment of E. nipponicum. We observed a significant dose-dependent downregulation of the expression of TNF-α and IL-10 cytokines. The observed suppression of TNF-alpha expression by rEnStef could result in decreased pathogen control, which might in turn lead to increased rates of secondary bacterial infections in fish infected by E. nipponicum.


Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma.
Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.