Robotic Proctectomy: Beyond the Initial Learning Curve.
Multiple authors have described an initial learning curve (LC) for robotic proctectomy (RP), but there is scant literature regarding continued technical progression beyond this stage. Total operating time is the most commonly used metric to measure proficiency. Our goal was to examine RP experience after the initial LC looking for evidence of further technical progression. We reviewed our robotic surgery database for a single surgeon during operations 100 through 550 to identify 83 RPs for tumor. These were divided into quartiles by series order, indicating surgeon experience level over time. Demographics and outcomes were compared among the groups. We defined percent console time (PCT) as a new metric. PCT was defined as console time divided by total operative time (TOT). From March 2014 through March 2019, 450 robotic colorectal operations were performed, including 83 RPs for polyp or cancer. No significant differences were found among the quartiles in regard to demographics, tumor features, hospital stay, conversions, or readmissions. As experience was gained, there were significant increases in intracorporeal anastomosis (ICA), TOT, and PCT. Complications decreased with experience. Number of lymph nodes in the specimen increased. On multivariate analysis, later experience group, body mass index ≥30, and ICA were associated with increased PCT. ICA became a routine part of RP after the initial LC, with increases in TOT and PCT. Number of lymph nodes increased and number and severity of complications decreased with experience. Increased PCT may indicate increased expertise during RP.


Neoantigen Discovery in Human Cancers.
Cancer is caused by alterations to DNA that ultimately are translated into altered proteins with unique amino acid sequences when compared with their counterparts in normal cells. By inference, these altered proteins have the potential to elicit immune responses such as T-cell recognition, if properly presented by the immune system following protein degradation and major histocompatibility complex binding. Historically, identifying tumor-specific mutant antigens was painstaking work that involved molecular cloning and immune screening. This scenario has changed dramatically in the last few years as new sequencing technology combined with computational data analysis can identify the unique tumor peptide sequences, and algorithmic evaluation of these novel peptides can estimate their binding affinity to the major histocompatibility complex haplotypes encoded by each genome. This process can identify unique neoantigens in each cancer, either as a means of characterizing the overall neoantigen load or as a precursor to designing a personalized cancer vaccine. An overview of the data and analysis methods used to identify cancer neoantigens will be presented along with an in-depth consideration of the nuances of each step.


[Utilization of an ELISA technic for the quantification of antipoliovirus antibodies in human sera].
A double antibody enzyme linked immunosorbent assay (ELISA) was elaborated for detection of poliovirus antibodies in human sera. The IgG to be titrated were immunoabsorbed by capture on the solid phase. The antigens used were obtained from vero cell cultures (green Monkey Kidney Cells). The reaction was followed by adding rabbit antipoliovirus serum, then sheep Fab fragment prepared against rabbit IgG and labelled with horse radish peroxidase. Ortho-tolidine was used as the chromogen substrate to reveal the reaction. This enabled a first reading with the naked eye. This technique allows to keep a better track of the poliomyelitis immunization.


Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice.
Subarachnoid hemorrhage (SAH) results in many brain dysfunctions and the neuroprotective function of puerarin after brain damage has been demonstrated in several studies. But whether puerarin can reduce brain nerve damage after SAH is not clear.In this study, we hypothesized that puerarin had the neuroprotective effect after SAH, and this protection could be mediated by bothBcl-2/Bax/Cleaved caspase-3 and SIRT3/SOD2 apoptotic signaling pathways. First, we used neurological score, brain water content and so on to detect the neurological deficits after SAH. Then apoptosis neuron rate was detected by TUNEL staining. Western blot was carried out to explore the alteration of Blc-2, Bax, cleaved caspase-3 and Sirt3.Also, ROS acitivity and As-lysine level of SOD2 should be detected with assays. We demonstrate that puerarin attenuated the neurological deficits, effectively relieves cerebral edema, and reduce BBB disruption in SAH mice.And we revealed that a reduced rate of apoptosis neuron has been found out in puerarin treatment after SAH. In addition, obviously higher ratio of Blc-2/Bax and decreased expression of cleaved caspase-3 in puerarin-treated SAH micecomparing with vehicle-treated SAH animals had been found. Furthermore, puerarin effectively reversed these alterations in expression and inhibits ROSproduction induced by SAH. Also, puerarin can increase SOD activation after SAH and protect the expression of Sirt3 after SAH. In coclusion, puerarin can provide potential neuroprotection from the SAH damages, and can be act as a novel therapy for SAH.


[Problems of indications for the treatment of aneurysm of the visceral arteries].
The authors report the clinical history and the treatment of 5 patients with visceral artery aneurysms. The celiac trunk, the common hepatic artery, the inferior pancreaticoduodenal artery and the splenic artery (in 2 different patients) were affected by the aneurysmal disease. Various techniques have been employed in the successful treatment of these patients: radiological embolization of the celiac trunk aneurysms, Dacron graft reconstruction of the common hepatic artery aneurysm, endosaccular ligature and PTFE patching of the inferior pancreatico-duodenal artery aneurysm, endosaccular ligature in one of the two splenic artery aneurysm and simple ligature and splenectomy in the remainder splenic artery aneurysm. Early diagnosis is important in these lesions, because of the trend toward rupture and subsequent high mortality rate. Ultrasonography (US), Computed Tomography (CT) and Magnetic Resonance (MR) are very helpful as diagnostic tools, however angiography represents the method of choice since it could be the first step of the embolization treatment. Furthermore angiography is useful for detection of associated visceral lesions and for the study of collateral blood supply. Treatment choice depends on visceral artery aneurysms localization, the presence of associate lesions and the possible general contraindications. In the latter case, radiological embolization could be the first-choice treatment.


Epigenetic and Genetic Contributions to Adaptation in Chlamydomonas.
Epigenetic modifications, such as DNA methylation or histone modifications, can be transmitted between cellular or organismal generations. However, there are no experiments measuring their role in adaptation, so here we use experimental evolution to investigate how epigenetic variation can contribute to adaptation. We manipulated DNA methylation and histone acetylation in the unicellular green alga Chlamydomonas reinhardtii both genetically and chemically to change the amount of epigenetic variation generated or transmitted in adapting populations in three different environments (salt stress, phosphate starvation, and high CO2) for two hundred asexual generations. We find that reducing the amount of epigenetic variation available to populations can reduce adaptation in environments where it otherwise happens. From genomic and epigenomic sequences from a subset of the populations, we see changes in methylation patterns between the evolved populations over-represented in some functional categories of genes, which is consistent with some of these differences being adaptive. Based on whole genome sequencing of evolved clones, the majority of DNA methylation changes do not appear to be linked to cis-acting genetic mutations. Our results show that transgenerational epigenetic effects play a role in adaptive evolution, and suggest that the relationship between changes in methylation patterns and differences in evolutionary outcomes, at least for quantitative traits such as cell division rates, is complex.


Effective treatment of leg vein telangiectasia with a new 940 nm diode laser.
A variety of lasers have been used in an attempt to treat leg vein telangiectasia To evaluate the feasibility of a new 940 nm diode laser for the treatment of leg vein telangiectasia. Thirty-one patients with leg vein telangiectasia were treated with a diode laser; 26 of these with 940 nm, 300-350 J/cm2, 40-70 msec, 1.0 mm handpiece, one pass, and 5 of these with 940 nm, 815 J/cm2, 50 msec, 0.5 mm handpiece, one pass. Each subject had three treatments of the same site at 4-week intervals. Photographs taken before and 4 weeks after the last treatment were evaluated by two independent observers for vessel clearance. In those 26 patients treated with a fluence of 300-350 J/cm2, a vessel clearance of greater than 50% was achieved in 20 patients (76%), 12 of these patients had clearance rates greater than 75%. A clearance rate of less than 50% was obtained in six patients, with three of these patients showing responses of less than 25%. In five patients treated with a fluence of 815 J/cm2 a clearance rate of more than 75% was observed. In this preliminary study a 940 nm diode laser was shown to be safe and effective for the treatment of leg vein telangiectasia.


Estimating Individual-Level Risk in Spatial Epidemiology Using Spatially Aggregated Information on the Population at Risk.
We propose a novel alternative to case-control sampling for the estimation of individual-level risk in spatial epidemiology. Our approach uses weighted estimating equations to estimate regression parameters in the intensity function of an inhomogeneous spatial point process, when information on risk-factors is available at the individual level for cases, but only at a spatially aggregated level for the population at risk. We develop data-driven methods to select the weights used in the estimating equations and show through simulation that the choice of weights can have a major impact on efficiency of estimation. We develop a formal test to detect non-Poisson behavior in the underlying point process and assess the performance of the test using simulations of Poisson and Poisson cluster point processes. We apply our methods to data on the spatial distribution of childhood meningococcal disease cases in Merseyside, U.K. between 1981 and 2007.


A psychometric experiment in causal inference to estimate evidential weights used by epidemiologists.
A psychometric experiment in causal inference was performed on 159 Australian and New Zealand epidemiologists. Subjects each decided whether to attribute causality to 12 summaries of evidence concerning a disease and a chemical exposure. The 1,748 unique summaries embodied predetermined distributions of 19 characteristics generated by computerized evidence simulation. Effects of characteristics of evidence on causal attribution were estimated from logistic regression, and interactions were identified from a regression tree analysis. Factors with the strongest influence on the odds of causal attribution were statistical significance (odds ratio = 4.5 if 0.001 < or = P < 0.05 and 7.2 if P < 0.001, vs P > or = 0.05); refutation of alternative explanations (odds ratio = 8.1 for no known confounder vs none adjusted); strength of association (odds ratio = 2.0 if 1.5 < relative risk < or = 2.0 and 3.6 if relative risk > 2.0, vs relative risk < or = 1.5); and adjunct information concerning biological, factual, and theoretical coherence. The refutation of confounding reduced the cutpoint in the regression tree for decision-making based on strength of association. The effect of the number of supportive studies reached saturation after it exceeded 12 studies. There was evidence of flawed logic in the responses concerning specificity of effects of exposure and a tendency to discount evidence if the P-value was a "near miss" (0.050 < P < 0.065). Evidential weights based on regression coefficients for causal criteria can be applied to actual scientific evidence.


[Abscess in the posterior third of the tongue. A clinical case].
A case of lingual abscess visualized by computed tomography is reported. The review of the literature demonstrated the difficulty of diagnosing these cases. Protection and surveillance of the upper airways is important. Computed tomography is the key to diagnosis.


The relationship between electronic health records user interface features and data quality of patient clinical information: an integrative review.
Electronic health records (EHRs) user interfaces (UI) designed for data entry can potentially impact the quality of patient information captured in the EHRs. This review identified and synthesized the literature evidence about the relationship of UI features in EHRs on data quality (DQ). We performed an integrative review of research studies by conducting a structured search in 5 databases completed on October 10, 2022. We applied Whittemore & Knafl's methodology to identify literature, extract, and synthesize information, iteratively. We adapted Kmet et al appraisal tool for the quality assessment of the evidence. The research protocol was registered with PROSPERO (CRD42020203998). Eleven studies met the inclusion criteria. The relationship between 1 or more UI features and 1 or more DQ indicators was examined. UI features were classified into 4 categories: 3 types of data capture aids, and other methods of DQ assessment at the UI. The Weiskopf et al measures were used to assess DQ: completeness (n = 10), correctness (n = 10), and currency (n = 3). UI features such as mandatory fields, templates, and contextual autocomplete improved completeness or correctness or both. Measures of currency were scarce. The paucity of studies on UI features and DQ underscored the limited knowledge in this important area. The UI features examined had both positive and negative effects on DQ. Standardization of data entry and further development of automated algorithmic aids, including adaptive UIs, have great promise for improving DQ. Further research is essential to ensure data captured in our electronic systems are high quality and valid for use in clinical decision-making and other secondary analyses.


[Sarcomas management network in France].
Goals of network structuration is to organize and improve outcomes for people with sarcoma. While it is difficult to predict the influence of that structuration, it is assumed that advances in health care organization will result in improvements in patient outcomes. Aims of such a network care are multiple: to offer a high level of care to all patients, at diagnostic level as well as at therapeutic level, to improve the skill of doctors to facilitate updating knowledge and to reinforce clinical research. On the other hand, it is a time consuming project for all actors, technical material is to be installed to connect all participants, heavy investments which are to be accurately assessed. The GSF-GETO (Groupe sarcome français-Groupe d'étude sur les tumeurs osseuses) started in that way, based on the role of Multidisciplinary Concertation Meeting as the cement of a national network.


Toxoids of Pseudomonas aeruginosa toxin A: production by chemical and genetic means.
Several toxin A toxoids were produced by reacting purified toxin A with formalin or formalin-lysine. Treatment with formalin alone resulted in a 1,000-fold decrease in cytotoxicity of toxin A without adversely affecting enzymatic activity. The antigenicity was moderately altered, but immunogenicity appeared to be unaffected, as evidenced by the ability of the toxoid to elicit good titers of neutralizing antibody. However, on removal of formalin and after storage at 37 C, formol toxoid showed a partial reversion to toxicity. The addition of lysine to formalin-toxin A mixtures increased the rate and extent of detoxification and destroyed enzymatic activity. Although the formalin-lysine toxoid did not revert to toxicity, it displayed a reduced immunogenicity even when employed with an adjuvant. On the basis of these results, an alternative method was selected for detoxification of toxin A. A mutant (PAO-PR1), which produces a CRM protein (CRM 66), was isolated after chemical mutagenesis. CRM 66 has the same molecular weight as toxin A and is antigenically indistinguishable from it. The cytotoxicity and lethality to mice of CRM 66 was found to be greatly reduced in comparison to that of toxin A, a difference apparently due to a reduction in enzymatic activity.


A concise and persistent feature to study brain resting-state network dynamics: Findings from the Alzheimer's Disease Neuroimaging Initiative.
Alzheimer's disease (AD) is the most common type of dementia in the elderly with no effective treatment currently. Recent studies of noninvasive neuroimaging, resting-state functional magnetic resonance imaging (rs-fMRI) with graph theoretical analysis have shown that patients with AD and mild cognitive impairment (MCI) exhibit disrupted topological organization in large-scale brain networks. In previous work, it is a common practice to threshold such networks. However, it is not only difficult to make a principled choice of threshold values, but also worse is the discard of potential important information. To address this issue, we propose a threshold-free feature by integrating a prior persistent homology-based topological feature (the zeroth Betti number) and a newly defined connected component aggregation cost feature to model brain networks over all possible scales. We show that the induced topological feature (Integrated Persistent Feature) follows a monotonically decreasing convergence function and further propose to use its slope as a concise and persistent brain network topological measure. We apply this measure to study rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative and compare our approach with five other widely used graph measures across five parcellation schemes ranging from 90 to 1,024 region-of-interests. The experimental results demonstrate that the proposed network measure shows more statistical power and stronger robustness in group difference studies in that the absolute values of the proposed measure of AD are lower than MCI and much lower than normal controls, providing empirical evidence for decreased functional integration in AD dementia and MCI.


Predictors of Severe Clinical Course in Children With Carbon Monoxide Poisoning.
Carbon monoxide (CO) is a gas, which is produced by incomplete combustion of hydrocarbon-containing substances, and causes significant tissue and organ damage in the common event of CO poisoning. This study aims to evaluate the demographic, clinical, and laboratory characteristics of patients diagnosed with CO poisoning in the emergency department and to determine the factors associated with severe course in the acute phase of poisoning. A total of 331 patients diagnosed with CO poisoning in Hacettepe University Children's Hospital, Pediatric Emergency Unit, between January 2004 and March 2014 were included in the study. Their demographic characteristics, presenting complaints, physical examination findings, Glasgow Coma Scale scores, carboxyhemoglobin, leukocyte, hemoglobin, troponin T, pH and lactate levels, type of treatment (normobaric or hyperbaric oxygen), intensive care unit admissions, and outcome of poisoning were investigated. Ninety-three patients were given hyperbaric oxygen. Fifty-one patients were admitted to the pediatric intensive care unit, 18 patients have had a severe clinical course, and 6 patients have died. The risk factors associated with severe disease course were determined to be low Glasgow Coma Scale score, high leukocyte count, and high troponin T levels at presentation. Glasgow Coma Scale score, leukocyte count, and troponin T level may be beneficial in predicting clinical outcomes and tailoring therapy in children with CO poisoning.


Assessment of metal pollution associated with an alteration area: Old Gümüşhane, NE Black Sea.
The objective of this study was to determine the potential environmental risks associated with the Kirkpavli (Old Gümüşhane in northern Turkey) alteration area by quantifying pollution in soil. The Kirkpavli (Old Gümüşhane) alteration area is situated at the south of the deposit with the same name of gold-silver-bearing lead, zinc, and copper in the southern part of the Black Sea Tectonic Unit (Eastern Pontides). In this study, 28 soil samples acquired from the alteration area were analyzed for contents of some main elements including lead (Pb), copper (Cu), zinc (Zn), cadmium (Cd), cobalt (Co), manganese (Mn), nickel (Ni), and arsenic (As). Contents of the elements in the area were determined, and high values were obtained such as 1,171 mg/kg for As, 12.4 mg/kg for Cd, 77.3 mg/kg for Co, 341 mg/kg for Cu, 1,172 mg/kg for Mn, 51.9 mg/kg for Ni, 3,725 mg/kg for Pb, and 880 mg/kg for Zn. Soil contamination was appraised on the basis of Geoaccumulation Index (I geo), Enrichment Factor (EF), Pollution Index, and Integrated Pollution Index. The calculated results of I geo, EF, and PI of the elements can be shown in descending order of parameters as As > Pb > Cd > Zn > Cu > Co > Mn. The parameters for some of these elements indicated extremely high contamination (I geo > 5), extremely high enrichment (EF > 40), and high pollution (PI > 3). High I geo, EF, and PI values of As, Pb, and Cd in the soil samples mean that soil pollution is typically associated with alteration area. Considering its location and the results of this study, the Kirkpavli alteration area is a significant source of pollution and may have ecotoxicological effects on terrestrial, groundwater, and aquatic ecosystems in the region.


[The quantitative myoglobin assay for forensic medical expertise].
The results of quantitative determination of the myoglobin (MG) levels in the cadaveric blood are presented. The blood samples were collected from the subjects who were affected by or died from various diseases. Modern forensic medical practice requires the use of new methods for the study and diagnostics of intravital traumatic damage and elucidation of the concrete cause of death enabling the law-enforcement agencies to rapidly and effectively investigate the offences against the person. A total of 161 cases were analysed. The myoglobin levels were shown to be highly variable among the casualties. They were less dependent on the concrete form of injury or disease and were in the first time related to the rate at which death approaches and the state of blood circulation. The MG level was shown to drop appreciably in the case of sudden cardiac arrest whereas a prolonged agonal period was associated with its significant increase.


Preconditioning and stem cell survival.
The harsh ischemic and cytokine-rich microenvironment in the infarcted myocardium, infiltrated by the inflammatory and immune cells, offers a significant challenge to the transplanted donor stem cells. Massive cell death occurs during transplantation as well as following engraftment which significantly lowers the effectiveness of the heart cell therapy. Various approaches have been adopted to overcome this problem nevertheless with multiple limitations with each of these current approaches. Cellular preconditioning and reprogramming by physical, chemical, genetic, and pharmacological manipulation of the cells has shown promise and "prime" the cells to the "state of readiness" to withstand the rigors of lethal ischemia in vitro as well as posttransplantation. This review summarizes the past and present novel approaches of ischemic preconditioning, pharmacological and genetic manipulation using preconditioning mimetics, recombinant growth factor protein treatment, and reprogramming of stem cells to overexpress survival signaling molecules, microRNAs, and trophic factors for intracrine, autocrine, and paracrine effects on cytoprotection.


[Nondestructive analysis of protein and fat in whole-kernel soybean by NIR].
Near-infrared diffusion reflectance spectroscopy is a fast technique that can provide component information about intact soybean samples. We have combined this technique with partial least-squares (PLS) regression to perform a quantitative determination of protein and fat contents in soybean samples. In calibration set, the NIR model determination coefficient R2 of protein and fat is 0.9930 and 0.9752 respectively, and the relative standard deviation (RSD) is 0.76% and 1.3% respectively. The correlation coefficient r of validation set is 0.9473 and 0.8695 respectively. This NIR model is used to predict the contents of protein and fat in 264 soybean samples, using R-error to assess the deviation of analysis results. The minimum RSD of prediction of protein and fat is 0.04% and 2.46% respectively, and the maximum RSD of prediction of protein and fat is 2.45% and 4.25% respectively. These results are of great importance in early screening of crop breeding.


[Effect of the alpha 1-receptor blocker prazosin and the beta 1-receptor blocker acebutolol and their combination on blood pressure and pressure rate product. Ergometric studies of hypertensive patients].
The cardiovascular risk of hypertension depends not only on blood pressure under resting conditions, but particularly on blood pressure increases induced by daily physical and emotional activity. Therefore, the ability of the beta 1-receptor antagonist acebutolol (400 mg/day) and of the alpha 1-receptor antagonist prazosin (4 mg/day) to reduce exercise-induced increases in blood pressure and pressure-rate product during and after standardized ergometric work (50-100 W) was compared in an intrapatient study including 20 outpatients with arterial hypertension (WHO stage 1-2) aged 29-55 years. Both drugs resulted in a significant reduction of systolic (p less than 0.01) and diastolic (p less than 0.001) blood pressure at rest. However, systolic blood pressure (p less than 0.001) and pressure-rate product (p less than 0.001) during exercise were only significantly reduced by acebutolol. The strongest blood pressure lowering effect under all conditions could be achieved by the combination of prazosin and acebutolol. From these findings it is concluded that: (1) beta-adrenoreceptor-blocking agents are the drugs of first choice in the baseline therapy of mild to moderate arterial hypertension, and (2) prazosin potentiates the antihypertensive effect of beta-blocking agents. This therapeutic regimen is recommended especially for hypertensives with ischemic heart disease, because prazosin fails to reduce pressure-rate product as a measure of myocardial O2-consumption.


RARgamma acts as a tumor suppressor in mouse keratinocytes.
All-trans retinoic acid (RA), the principle biologically active form of vitamin A, is essential for many developmental process as well as homeostasis in the adult. Many lines of evidence also suggest that RA, acting through the RA receptors (RARs), can also suppress growth of tumors of diverse origin. To assess directly the role of the RARs in a model of epidermal tumorigenesis, we investigated the incidence of tumor formation using keratinocytes lacking specific RAR types. Our data suggest that loss of RARgamma, but not RARalpha, predisposed keratinocytes to v-Ha-Ras-induced squamous cell carcinoma. We also found that ablation of RARgamma, but not RARalpha, abolished RA-induced cell cycle arrest and apoptosis in these keratinocytes. Reconstitution of receptor expression into RAR-null cells restored sensitivity to RA, and reversed the tumorigenic potential of receptor-deficient keratinocytes. These data strongly support a tumor suppressor effect for the RARs, in particular endogenous RARgamma, in murine keratinocytes.


Tuned range-separated hybrid functionals in the symmetry-adapted perturbation theory.
The aim of this study is to present a performance test of optimally tuned long-range corrected (LRC) functionals applied to the symmetry-adapted perturbation theory (SAPT). In the present variant, the second-order energy components are evaluated at the coupled level of theory. We demonstrate that the generalized Kohn-Sham (GKS) description of monomers with optimally tuned LRC functionals may be essential for the quality of SAPT interaction energy components. This is connected to the minimization of a many-electron self-interaction error and exemplified by two model systems: polyacetylenes of increasing length and stretching of He 3 (+). Next we provide a comparison of SAPT approaches based on Kohn-Sham and GKS description of the monomers. We show that LRC leads to results better or comparable with the hitherto prevailing asymptotically corrected functionals. Finally, we discuss the advantages and possible limitations of SAPT based on LRC functionals.


Healthcare reform and its impact on data collection and dissemination.
Making quality- and outcome-related information available to healthcare consumers and purchasers is a central tenet of the Health Security Act, and few in healthcare oppose this provision of the Act--in concept, says Robert Hartley, MD, MBA, Vice President, Christian Health Services. Consumers and purchasers need such information to make informed choices about their healthcare options. However, the Act does not make clear how or by whom quality measurement data are to be collected and disseminated, nor by what criteria healthcare providers will be held accountable.


[Friedrich Wilhelm I and porphyria].
Historical evidence has been collected attempting to diagnose members of royal houses, perhaps most publicized by Macalpine and Hunter (1969) for George III and his assumed porphyria, claiming that his insanity was a classic case of thereof. This rare metabolic disease presents with a variety of signs and symptoms: skin disease, abdominal pain, tachycardia, and neuro-psychiatric findings. The porphyrias are hereditary and since George III and Frederick William I share ancestors it seemed reasonable to investigate if the latter may also have suffered from porphyria. The pathography of both kings is meticulous, showing for both that abdominal pain, erratic behavior, restlessness, and discolored urine were frequently observed and complete recovery interictally was common. Intercurrent illnesses, fasting, alcohol and even tobacco smoking have been shown to be inducers of attacks and these risk factors are well documented in royal history.--The diagnosis of porphyria was not recognized then and other names were used, such as Cachexia hypochondriaca, Asthma spasmodico flatulentum, dolores arthritici.--We propose that Frederick William I suffered from an inducible porphyria.


Abnormal prion protein in genetically resistant sheep from a scrapie-infected flock.
The central molecular event in transmissible spongiform encephalopathies, such as scrapie in sheep, is the accumulation in tissues of an abnormal isoform of the cellular prion protein. A previous investigation of 26 sheep showed that the accumulation of PrP(res) in brain correlated more with the prnp genotype than with the severity of the clinical disease. Here, the ability of a sandwich ELISA to detect PrP(res) distribution in the brain was demonstrated. Immunohistochemistry also strongly supported the hypothesis that the dorsal motor nucleus of the vagus nerve is the possible entry site in the brain for the scrapie agent. Remarkably, three asymptomatic (or possibly asymptomatic for scrapie) sheep carrying an allele known to be associated with clinical scrapie resistance (ARR), which were negative for the detection of PrP(res) by Western blotting and immunohistochemistry, were positive for the presence of PrP(res) by ELISA, raising the possibility of carriers resistant to the disease and possibly contributing to the persistence of scrapie in certain flocks.


A robust method of nuclei isolation for single-cell RNA sequencing of solid tissues from the plant genus Populus.
Single-cell transcriptome analysis has been extensively applied in humans and animal models to uncover gene expression heterogeneity between the different cell types of a tissue or an organ. It demonstrated its capability to discover key regulatory elements that determine cell fate during developmental programs. Single-cell analysis requires the isolation and labeling of the messenger RNA (mRNA) derived from each cell. These challenges were primarily addressed in mammals by developing microfluidic-based approaches. For plant species whose cells contain cell walls, these approaches have generally required the generation of isolated protoplasts. Many plant tissues' secondary cell wall hinders enzymatic digestion required for individual protoplast isolation, resulting in an unequal representation of cell types in a protoplast population. This limitation is especially critical for cell types located in the inner layers of a tissue or the inner tissues of an organ. Consequently, single-cell RNA sequencing (scRNA-seq) studies using microfluidic approaches in plants have mainly been restricted to Arabidopsis roots, for which well-established procedures of protoplast isolation are available. Here we present a simple alternative approach to generating high-quality protoplasts from plant tissue by characterizing the mRNA extracted from individual nuclei instead of whole cells. We developed the protocol using two different plant materials with varying cellular complexity levels and cell wall structure, Populus shoot apices, and more lignified stems. Using the 10× Genomics Chromium technology, we show that this procedure results in intact mRNA isolation and limited leakage, with a broad representation of individual cell transcriptomes.


Cowpox virus infection in cats: ABCD guidelines on prevention and management.
The misnomer 'cowpox' has historical roots: cats rather acquire the virus from small rodents. It has a wide host spectrum (including man) and causes skin lesions, predominantly on the head and paws. Progressive proliferative ulcerations in kittens and immunosuppressed cats may take a fatal course. Cat owners should be informed about the zoonotic risk.


Automated analysis of invadopodia dynamics in live cells.
Multiple cell types form specialized protein complexes that are used by the cell to actively degrade the surrounding extracellular matrix. These structures are called podosomes or invadopodia and collectively referred to as invadosomes. Due to their potential importance in both healthy physiology as well as in pathological conditions such as cancer, the characterization of these structures has been of increasing interest. Following early descriptions of invadopodia, assays were developed which labelled the matrix underneath metastatic cancer cells allowing for the assessment of invadopodia activity in motile cells. However, characterization of invadopodia using these methods has traditionally been done manually with time-consuming and potentially biased quantification methods, limiting the number of experiments and the quantity of data that can be analysed. We have developed a system to automate the segmentation, tracking and quantification of invadopodia in time-lapse fluorescence image sets at both the single invadopodia level and whole cell level. We rigorously tested the ability of the method to detect changes in invadopodia formation and dynamics through the use of well-characterized small molecule inhibitors, with known effects on invadopodia. Our results demonstrate the ability of this analysis method to quantify changes in invadopodia formation from live cell imaging data in a high throughput, automated manner.


Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden.
To examine the relation between connective tissue disease and related conditions and breast implants. Retrospective cohort study of all women in the Swedish national inpatient registry who underwent breast augmentation surgery with artificial implants during 1964-93, compared with women who underwent breast reduction surgery during the same period. Sweden. 7442 women with implants for cosmetic reasons or for reconstruction after breast cancer surgery and 3353 women with breast reduction surgery. Subsequent hospitalisation for definite connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and Sjögren's syndrome) or related disorders. 29 women with implants were hospitalised for definite connective tissue disease compared with 25.5 expected based on general population rates (standardised hospitalisation ratio 1.1 (95% confidence interval 0.8 to 1.6)). There were no diagnoses of systemic sclerosis, and no significant excess in risk for polymyalgia rheumatica, fibromyalgia, and several related disorders. Among women who underwent breast reduction surgery, 14 were hospitalised for definite connective tissue disease compared with 10.5 expected (standardised hospitalisation ratio 1.3 (0.7 to 2.2)). Compared with the breast reduction group, women with breast implants showed a slight reduction for all definite connective tissue disease (relative risk 0.8 (95% confidence interval 0.5 to 1.4)). This large nationwide cohort study shows no evidence of association between breast implants and connective tissue disease.


Thymoquinone alleviates doxorubicin induced acute kidney injury by decreasing endoplasmic reticulum stress, inflammation and apoptosis.
Doxorubicin (DOX) is used as an anticancer drug despite its many side effects. Thymoquinone (THQ) is a plant-derived substance that exhibits antioxidant and anti-inflammatory properties. We investigated the protective effects of THQ on DOX induced nephrotoxicity in rats. Rats were divided into five groups of eight: group 1, untreated control; group 2, olive oil group given olive oil intraperitoneally (i.p.) for 14 days; group 3, THQ group given 10 mg/kg THQ i.p. for 14 days; group 4, DOX group given a single dose of 15 mg/kg DOX i.p. on day 7 of experiment; group 5, DOX + THQ given 10 mg/kg THQ i.p. for 14 days and 15 mg/kg DOX i.p. on day 7. Kidney tissues were evaluated for histopathology. Caspase-3, IL-17, GRP78 and TNF-α immunostaining was used to determine the expression levels of these proteins among the groups. The TUNEL method was used to determine the apoptotic index. Total antioxidant status (TAS), total oxidant status (TOS), and TNF-α and TGF-β1 levels in kidney tissue were measured using ELISA assay. Histopathologic damage, caspase-3, IL-17, GRP78 and TNF-α immunoreactivity, TUNEL positive cells, TOS, TNF-α and TGF-β1 levels were increased in group 4 compared to group 1. The TAS of group 4 decreased compared to group 1. We found decreased caspase-3, IL-17, GRP78 and TNF-α expressions and TUNEL positive cells in group 5 compared to group 4. In rats given DOX, THQ reduced kidney damage by suppressing endoplasmic reticulum stress, inflammation and apoptosis pathways.


Prediction of egg freshness during storage using electronic nose.
The aim of the present study was to investigate the potential of a fast gas chromatography (GC) e-nose for freshness discrimination and for prediction of storage time as well as sensory and internal quality changes during storage of hen eggs. All samples were obtained from the same egg production farm and stored at 20 °C for 20 d. Egg sampling was conducted every 0, 3, 6, 9, 12, 16, and 20 d. During each sampling time, 4 egg cartons (each containing 10 eggs) were randomly selected: one carton for Haugh units, one carton for sensory evaluation and 2 cartons for the e-nose experiment. The e-nose study included 2 independent test sets; calibration (35 samples) and validation (28 samples). Every sampling time, 5 replicates were prepared from one egg carton for calibration samples and 4 replicates were prepared from the remaining egg carton for validation samples. Sensors (peaks) were selected prior to multivariate chemometric analysis; qualitative sensors for principal component analysis (PCA) and discriminant factor analysis (DFA) and quantitative sensors for partial least square (PLS) modeling. PCA and DFA confirmed the difference in volatile profiles of egg samples from 7 different storage times accounting for a total variance of 95.7% and 93.71%, respectively. Models for predicting storage time, Haugh units, odor score, and overall acceptability score from e-nose data were developed using calibration samples by PLS regression. The results showed that these quality indices were well predicted from the e- nose signals, with correlation coefficients of R2 = 0.9441, R2 = 0.9511, R2 = 0.9725, and R2 = 0.9530 and with training errors of 0.887, 1.24, 0.626, and 0.629, respectively. As a result of ANOVA, most of the PLS model results were not significantly (P > 0.05) different from the corresponding reference values. These results proved that the fast GC electronic nose has the potential to assess egg freshness and feasibility to predict multiple egg freshness indices during its circulation in the supply chain.


Management of chest trauma.
Trauma is the leading cause of death worldwide. Approximately 2/3 of the patients have a chest trauma with varying severity from a simple rib fracture to penetrating injury of the heart or tracheobronchial disruption. Blunt chest trauma is most common with 90% incidence, of which less than 10% require surgical intervention of any kind. Mortality is second highest after head injury, which underlines the importance of initial management. Many of these deaths can be prevented by prompt diagnosis and treatment. What is the role of the thoracic surgeon in the management of chest trauma in severely injured patients? When should the thoracic surgeon be involved? Is there a place for minimal invasive surgery in the management of severely injured patients? With two case reports we would like to demonstrate how the very specific knowledge of thoracic surgeons could help in the care of trauma patients.


Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats.
Cardiometabolic syndrome occurs with obesity and consists of pathophysiological factors that increase the risk for cardiovascular events. Soluble epoxide hydrolase inhibition (sEHi) is a novel therapeutic approach that exerts renal and cardiovascular protection. Although sEHi as a therapeutic approach is promising, it could be more effective for the treatment of cardiometabolic syndrome when combined with peroxisome proliferator activated receptor γ (PPARγ) agonists. We hypothesized that the PPARγ agonist, rosiglitazone in combination with a sEHi (tAUCB) will provide synergistic actions to decrease blood pressure, improve vascular function, decrease inflammation, and prevent renal damage in spontaneously hypertensive obese rats (SHROB). SHROB were treated with rosiglitazone, tAUCB or the combination of tAUCB and rosiglitazone for four-weeks and compared with spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Blood pressure increased in SHROB (164 ± 7 mmHg) and decreased 10 mmHg when treated with rosiglitazone, tAUCB, or tAUCB and rosiglitazone. Mesenteric artery dilation to the K(ATP) channel opener pinacidil was attenuated in SHROB (E(Max) = 77 ± 7%), compared with WKY (E(Max) = 115 ± 19) and SHR (E(Max) = 93 ± 12%). Vasodilation to pinacidil was improved by rosiglitazone (E(Max) = 92 ± 14%) but not tAUCB. Renal macrophage infiltration increased in SHROB and significantly decreased with rosiglitazone or tAUCB and rosiglitazone treatment. Albuminuria was increased in SHROB (90 ± 20 mg/d) and was significantly decreased by the combination of tAUCB and rosiglitazone (37 ± 9 mg/d). Glomerular injury in SHROB was also significantly decreased by tAUCB and rosiglitazone. These results indicate that even though sEHi or PPARγ agonist have benefits when used individually, the combination is more beneficial for the multidisease features in cardiometabolic syndrome.


Fish oil supplementation during late pregnancy does not influence plasma lipids or lipoprotein levels in young adult offspring.
Nutritional influences on cardiovascular disease operate throughout life. Studies in both experimental animals and humans have suggested that changes in the peri- and early post-natal nutrition can affect the development of the various components of the metabolic syndrome in adult life. This has lead to the hypothesis that n-3 fatty acid supplementation in pregnancy may have a beneficial effect on lipid profile in the offspring. The aim of the present study was to investigate the effect of supplementation with n-3 fatty acids during the third trimester of pregnancy on lipids and lipoproteins in the 19-year-old offspring. The study was based on the follow-up of a randomized controlled trial from 1990 where 533 pregnant women were randomized to fish oil (n = 266), olive oil (n = 136) or no oil (n = 131). In 2009, the offspring were invited to a physical examination including blood sampling. A total of 243 of the offspring participated. Lipid values did not differ between the fish oil and olive oil groups. The relative adjusted difference (95% confidence intervals) in lipid concentrations was -3% (-11; 7) for LDL cholesterol, 3% (-3; 10) for HDL cholesterol, -1% (-6; 5) for total cholesterol,-4% (-16; 10) for TAG concentrations, 2%(-2; 7) for apolipoprotein A1, -1% (-9; 7) for apolipoprotein B and 3% (-7; 15) in relative abundance of small dense LDL. In conclusion, there was no effect of fish oil supplementation during the third trimester of pregnancy on offspring plasma lipids and lipoproteins in adolescence.


Comparison of AFLP and rep-PCR genomic fingerprinting with DNA-DNA homology studies: Xanthomonas as a model system.
The genus Xanthomonas contains a large number of strains, which have been characterized by a variety of phenotypic and genotypic classification methods. The Xanthomonas collection constitutes one of the largest groups of bacteria that have been characterized phylogenetically by DNA-DNA homology studies and genomic fingerprinting. Presently, a total genomic DNA-DNA homology value of 70% represents an internationally accepted criterion to define bacterial species levels. However, the complexity of DNA-DNA reassociation kinetics methods precludes the rapid analysis of large numbers of bacterial isolates, which is imperative for molecular microbial diversity studies. Therefore, the aim of this study was to compare more facile PCR-based genomic fingerprinting techniques, such as repetitive-sequence-based (rep)-PCR and AFLP genomic fingerprinting, to DNA-DNA hybridization studies. Using three different primer sets, rep-PCR genomic fingerprint patterns were generated for 178 Xanthomonas strains, belonging to all 20 previously defined DNA-DNA homology groups, and one Stenotrophomonas maltophilia strain. In addition, AFLP genomic fingerprints were produced for a subset of 80 Xanthomonas strains belonging to the 20 DNA-DNA homology groups and for the S. maltophilia strain. Similarity values derived from rep-PCR- and AFLP-generated fingerprinting analyses were calculated and used to determine the correlation between rep-PCR- or AFLP-derived relationships and DNA-DNA homology values. A high correlation was observed, suggesting that genomic fingerprinting techniques truly reveal genotypic and phylogenetic relationships of organisms. On the basis of these studies, we propose that genomic fingerprinting techniques such as rep-PCR and AFLP can be used as rapid, highly discriminatory screening techniques to determine the taxonomic diversity and phylogenetic structure of bacterial populations.


Electromyographic analysis of profound facial nerve paralysis following acoustic neuroma resection.
The aim of our retrospective study was to determine whether electromyographic findings (motor unit action potentials, MUAPs) can be used in long-term prognosis for profound facial nerve paralysis in patients whose nerve continuity is preserved during surgery for acoustic neuroma. The orbicularis oris, frontal, and orbicularis oculi muscles were examined for the occurrence of MUAPs in 48 such patients. In 30 patients who recovered from complete paralysis within 10 months after surgery, MUAPs in the first two muscles tended to precede the first sign of facial movement. MUAPs appeared in the orbicularis muscle in 80% of these patients at 1 month and in all at 5 months. In the frontal and orbicularis oculi muscles, MUAPs occurred in only 0-20% of these patients in the first month; within 3-5 months the number increased rapidly, and MUAPs were present in 95% of these patients at 10 months. In the remaining 18 patients with long-term complete paralysis (at least 1 year), MUAPs appeared solely in the orbicularis oris muscle: in 20% of these patients in the first month after surgery. While this number slowly rose, there was no period of rapid increase later. We conclude that the occurrence of MUAPs in the orbicularis oris and frontal muscles within 3 months of surgery indicates a good prognosis for reversal of facial nerve paralysis.


Outcome of managing impotence in clinical practice.
Outside of controlled clinical trials, the outcome of treatment for unselected men with impotence is uncertain. This study aims to describe the clinical course of consecutive, unselected men referred to a specialist endocrinology private practice with a primary diagnosis of impotence. Consecutive men referred with a primary diagnosis of impotence between June 1995 and December 1997 were studied. After initial evaluation and appropriate investigation, treatment with testosterone in hypogonadal men and instruction in the use of a vacuum device and intracavernosal alprostadil (Caverject) in all men was offered. All men were followed up by telephone and/or questionnaire about erection outcome three to twelve months later. Nineteen diabetic men, aged 53.1+/-8.2 years and forty non-diabetic men, aged 54.8+/-11.6 years were seen. Follow-up information beyond three months was complete in fifty-three (90%). Eighteen eugonadal men chose no further therapy and four of these men had spontaneous return of erections. Eight men were hypogonadal and potency returned in two of six men treated with replacement testosterone. Nine men used the vacuum device, which was effective in three of them. Forty-one men had a trial of Caverject injection, which was effective in twenty-eight. Only twelve of these men used Caverject for longer than six months. Return of erections with therapy beyond three months in unselected men with impotence is successful in only about one-third. Unexpected hypogonadism is relatively common in impotent men, but testosterone replacement therapy has a low rate of improving erections. New therapies for impotence need careful follow-up studies to assess their effectiveness in clinical practice.


The realistic performance achievable with mycobacterial automated culture systems in high and low prevalence settings.
Diagnostic tests are generally used in situations with similar pre-test probability of disease to where they were developed. When these tests are applied in situations with very different pre-test probabilities of disease, it is informative to model the likely implications of known characteristics of test performance in the new situation. This is the case for automated Mycobacterium tuberculosis (MTB) liquid culture systems for tuberculosis case detection which were developed and are widely used in low burden settings but are only beginning to be applied on a large scale in high burden settings. Here we model the performance of MTB liquid culture systems in high and low tuberculosis (TB) prevalence settings using detailed published data concentrating on the likely frequency of cross-contamination events. Our model predicts that as the TB prevalence in the suspect population increases there is an exponential increase in the risk of MTB cross-contamination events expected in otherwise negative samples, even with equivalent technical performance of the laboratories. Quality control and strict cross-contamination measures become increasingly critical as the burden of MTB infection among TB suspects increases. Even under optimal conditions the realistically achievable specificity of these systems in high burden settings will likely be significantly below that obtained in low TB burden laboratories. Liquid culture systems can play a valuable role in TB case detection in laboratories in high burden settings, but laboratory workers, policy makers and clinicians should be aware of the increased risks, independent of laboratory proficiency, of cross-contamination events in high burden settings.


[Diabetes mellitus: facts and hypotheses].
The paper summarizes the experience gained in examining diabetes mellitus and its complications in the experimental and clinical settings for many years. It forwards the basic aspects in the major problems of diabetology: etiology, pathogenesis, prevention, and therapy. The paper analyses the fate of some hypotheses advanced in different years and emphasizes new advances made in theory and practice of medicine.


Volatility of heavy metals during incineration of tannery sludge in the presence of chlorides and phosphoric acid.
Knowledge of the behaviour of heavy metals in the combustion process is a most important factor in selecting disposal alternatives for waste materials. Accordingly, in this work, the vaporization behaviour of highly concentrated heavy metals (Pb, Zn, Cu and Cr) in tannery sludge were investigated experimentally. The sludge was spiked with various chlorine compounds (i.e. PVC, FeCl3, CaCl2 and NaCl) and pre-treated with phosphoric acid in order to evaluate the capacity of enhancement and weakening of the volatility of the heavy metals contained in tannery sludge. The experimental results show that the vaporization percentages increased with increasing ratio of Cl/sludge and temperature, and the accelerating and increasing effect of the addition of chlorides on the vaporization percentage of heavy metals was dependent on the release capacity of chlorine radicals. The vaporization percentages of lead and zinc increased by 15-20%, whereas those of copper and chromium increased by only about 3 and 10% at 800 degrees C. However, heavy metals were not expected to be completely released in the combustion process in spite of the high ratio of Cl/sludge. Alternately, heavy metals contained in tannery sludge can be immobilized effectively by pre-treatment with phosphoric acid. When the 85% phosphoric acid accounted for 10% of dry basis of tannery sludge, the phosphate-treated sludge showed the lowest vaporization percentage of about 3-15% with formation of Ca18Cu3(PO4)14, Ca9Cr(PO4)7, Ca19Zn2(PO4)14 and PbMgP2O7 in the bottom ash.


Functional Relationship of ATP Hydrolysis, Presynaptic Filament Stability, and Homologous DNA Pairing Activity of the Human Meiotic Recombinase DMC1.
DMC1 and RAD51 are conserved recombinases that catalyze homologous recombination. DMC1 and RAD51 share similar properties in DNA binding, DNA-stimulated ATP hydrolysis, and catalysis of homologous DNA strand exchange. A large body of evidence indicates that attenuation of ATP hydrolysis leads to stabilization of the RAD51-ssDNA presynaptic filament and enhancement of DNA strand exchange. However, the functional relationship of ATPase activity, presynaptic filament stability, and DMC1-mediated homologous DNA strand exchange has remained largely unexplored. To address this important question, we have constructed several mutant variants of human DMC1 and characterized them biochemically to gain mechanistic insights. Two mutations, K132R and D223N, that change key residues in the Walker A and B nucleotide-binding motifs ablate ATP binding and render DMC1 inactive. On the other hand, the nucleotide-binding cap D317K mutant binds ATP normally but shows significantly attenuated ATPase activity and, accordingly, forms a highly stable presynaptic filament. Surprisingly, unlike RAD51, presynaptic filament stabilization achieved via ATP hydrolysis attenuation does not lead to any enhancement of DMC1-catalyzed homologous DNA pairing and strand exchange. This conclusion is further supported by examining wild-type DMC1 with non-hydrolyzable ATP analogues. Thus, our results reveal an important mechanistic difference between RAD51 and DMC1.


Relation of FGFR2 genetic polymorphisms to the association between oral contraceptive use and the risk of breast cancer in Chinese women.
The fibroblast growth factor receptor 2 gene (FGFR2) has been associated with the risk of breast cancer in multiple ethnic populations, and its effect has been suggested to be hormone-dependent. A large, 2-stage, population-based case-control study was conducted in urban Shanghai, China, during the periods of 1996-1998 and 2002-2005. Exposure and genotyping information from 2,073 patients with breast cancer and 2,084 age-matched population controls was available for evaluation of the interactions between FGFR2 polymorphisms and exogenous estrogen exposure in the development of breast cancer. A logistic regression model was used to compute adjusted odds ratios and 95% confidence intervals. Of 20 genotyped and 25 imputed single nucleotide polymorphisms (SNPs), 22 were significantly associated with breast cancer. Three genotyped SNPs in close linkage disequilibrium, rs2303568, rs3135730, and rs1078806, and an imputed SNP of rs755793 in complete linkage disequilibrium with other 8 SNPs were observed to interact significantly with oral contraceptive (OC) use. The SNP-cancer association was evident only among OC users, and the OC use was only associated with the risk of breast cancer among carriers of these minor alleles at these loci. These findings suggest that genetic variants in FGFR2 may modify the role of OC use in causing breast cancer in Chinese women.


[Role of different types of infraorbital nerve fibers in synaptic activation of masticatory muscle motoneurons].
The PSPs of the masseter and digastric motoneurons evoked by stimulation of the infraorbital nerve by stimuli from 1 to 10 thresholds were studied in cats anesthetized with chloraloze and nembutal. Masseter motoneurons were divided into two groups. The first group masseter motoneurons responded to 1-2.5 threshold infraorbital nerve stimulation by short latent EPSPs. An increase in the impulse strength to 3-9 thresholds led to appearance of IPSPs with 2.8-3.5 ms latency in these motoneurons. The second group masseter motoneurons responded to 3.9 threshold stimulation of the infraorbital nerve by IPSPs with 6.8 ms latency. The strength of stimuli below 3 thresholds evoked no PSPs in these neurons. Stimuli of 1.1-2.0 thresholds evoked EPSPs in digastric motoneurons but an increased stimulation led to generation of action potentials. It is supposed that existence of different inputs is a basis for functional diversity of jaw-closing and jaw-opening reflexes.


The mangrove nursery paradigm revisited: otolith stable isotopes support nursery-to-reef movements by Indo-Pacific fishes.
Mangroves and seagrass beds have long been perceived as important nurseries for many fish species. While there is growing evidence from the Western Atlantic that mangrove habitats are intricately connected to coral reefs through ontogenetic fish migrations, there is an ongoing debate of the value of these coastal ecosystems in the Indo-Pacific. The present study used natural tags, viz. otolith stable carbon and oxygen isotopes, to investigate for the first time the degree to which multiple tropical juvenile habitats subsidize coral reef fish populations in the Indo Pacific (Tanzania). Otoliths of three reef fish species (Lethrinus harak, L. lentjan and Lutjanus fulviflamma) were collected in mangrove, seagrass and coral reef habitats and analyzed for stable isotope ratios in the juvenile and adult otolith zones. δ(13)C signatures were significantly depleted in the juvenile compared to the adult zones, indicative of different habitat use through ontogeny. Maximum likelihood analysis identified that 82% of adult reef L. harak had resided in either mangrove (29%) or seagrass (53%) or reef (18%) habitats as juveniles. Of adult L. fulviflamma caught from offshore reefs, 99% had passed through mangroves habitats as juveniles. In contrast, L. lentjan adults originated predominantly from coral reefs (65-72%) as opposed to inshore vegetated habitats (28-35%). This study presents conclusive evidence for a nursery role of Indo-Pacific mangrove habitats for reef fish populations. It shows that intertidal habitats that are only temporarily available can form an important juvenile habitat for some species, and that reef fish populations are often replenished by multiple coastal habitats. Maintaining connectivity between inshore vegetated habitats and coral reefs, and conserving habitat mosaics rather than single nursery habitats, is a major priority for the sustainability of various Indo Pacific fish populations.


Grandiose narcissists and decision making: Impulsive, overconfident, and skeptical of experts-but seldom in doubt.
A substantial body of research has documented that grandiose narcissists are characterized by high self-esteem, a sense of personal superiority and entitlement, overconfidence, a willingness to exploit others for self-gain, and hostility and aggression when challenged. We report two studies (N = 452) that explore how these dispositions affect their decision making. We show that grandiose narcissists' overconfidence, impulsivity, and a willingness to ignore expert advice results in a higher likelihood of making a bad decision. In addition, after getting the wrong answer, grandiose narcissists are more likely to blame others and remain self-confident in their judgment.


[Cancer of the prostate revealed by hemospermia in a young man].
The authors report a case of prostatic cancer in a 50-year-old patient, for which the sole clinical manifestation was recurrent hemospermia. There was an undoubted connection, in this case, between the hemospermia and the cancer, which is rare. The treatment was endoscopic associated with cobalt therapy. The follow-up is four years.


Diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of atherosclerotic plaque composition in ex-vivo coronary specimens: a comparison with histology.
Both intravascular ultrasound and optical coherence tomography have been purported to accurately detect and characterize coronary atherosclerotic plaque composition. The aim of our study was to directly compare the reproducibility and diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of coronary plaque composition ex vivo as compared with histology. Intravascular ultrasound (20 MHz) and optical coherence tomography imaging was performed in eight heart specimens using motorized pullback. Standard histology using hematoxylin-eosin and van Gieson staining was performed on 4 mum thick slices. Each slice was divided into quadrants and accurately matched cross-sections were analyzed for the presence of fibrous, lipid-rich, and calcified coronary plaque using standard definitions for both intravascular ultrasound and optical coherence tomography and correlated with histology. After exclusion of 145/468 quadrants, we analyzed the remaining 323 quadrants with excellent image quality in each procedure. Optical coherence tomography demonstrated a sensitivity and specificity of 91/88% for normal wall, 64/88% for fibrous plaque, 77/94% for lipid-rich plaque, and 67/97% for calcified plaque as compared with histology. Intravascular ultrasound demonstrated a sensitivity and specificity of 55/79% for normal wall, 63/59% for fibrous plaque, 10/96% for lipid-rich plaque, and 76/98% for calcified plaque. Both intravascular ultrasound and optical coherence tomography demonstrated excellent intraobserver and interobserver agreement (optical coherence tomography: kappa=0.90, kappa=0.82; intravascular ultrasound: kappa=0.87, kappa=0.86). Optical coherence tomography is superior to intravascular ultrasound for the detection and characterization of coronary atherosclerotic plaque composition, specifically for the differentiation of noncalcified, lipid-rich, or fibrous plaque.


Validation of a minimal panel of antibodies for the diagnosis of malignant pleural mesothelioma.
We previously established the use of a minimal panel of antibodies as sufficient to diagnose most epithelial malignant mesothelioma (MPM). We aimed to validate this approach and investigate the utility of a D2-40 antibody. A series of 80 MPM patients selected for surgery and 21 consecutive patients with pleural metastatic carcinoma were included. A minimal panel of antibodies, consisting of calretinin, BG8 and CD15, and D2-40 was investigated. There were 61 epithelial and 19 biphasic MPM as well as 12 metastatic lung, six breast (5 ductal adenocarcinomas, 1 mixed ductal/lobular adenocarcinoma), two serous papillary ovarian carcinomas and one moderately differentiated colorectal adenocarcinoma. The sensitivity of positive calretinin labelling to confirm the diagnosis of MPM was 97.5%, while the 'diagnostic sensitivities' of lack of labelling for BG8 and CD15 were 91.3% and 97.5%, respectively. The use of calretinin, BG8 and CD15 resulted in correct classification in 97.5% of all MPMs. All MPM cases investigated showed at least focal positive D2-40 labelling. We have validated the usefulness of a minimal panel of antibodies with calretinin, BG8 and CD15 as the initial step to the diagnosis of MPM. D2-40 emerged as a helpful diagnostic tool for cases where our initial approach failed to conclusively diagnose MPM.


The Impact of Di-Isononyl Phthalate Exposure on Specialized Epithelial Cells in the Colon.
Di-isononyl phthalate (DiNP) is a high-molecular-weight phthalate commonly used as a plasticizer for polyvinyl chloride and other end products, such as medical devices and construction materials. Most of our initial exposure to DiNP occurs by ingestion of DiNP-contaminated foods. However, little is known about the effects of DiNP on the colon. Therefore, the goal of this study was to test the hypothesis that DiNP exposure alters immune responses and impacts specialized epithelial cells in the colon. To test this hypothesis, adult female mice were orally dosed with corn-oil vehicle control or doses of DiNP ranging from 20 µg/kg/d to 200 mg/kg/d for 10-14 days. After the dosing period, mice were euthanized in diestrus, and colon tissues and sera were collected for histological, genomic, and proteomic analysis of various immune factors and specialized epithelial cells. Subacute exposure to DiNP significantly increased protein levels of Ki67 and MUC2, expression of a Paneth cell marker (Lyz1), and estradiol levels in sera compared with control. Gene expression of mucins (Muc1, Muc2, Muc3a, and Muc4), Toll-like receptors (Tlr4 and Tlr5), and specialized epithelial cells (ChgA, Lgr5, Cd24a, and Vil1) were not significantly different between treatment groups and control. Cytokine levels of IL-1RA and CXCL12 were also not significantly different between DiNP treatment groups and control. These data reveal that DiNP exposure increases circulating estradiol levels and gene expression in specialized epithelial cells with immune response capabilities (eg, goblet and Paneth cells) in the mouse colon, which may initiate immune responses to prevent further damage in the colon.


Genome sequence reveals that Pseudomonas fluorescens F113 possesses a large and diverse array of systems for rhizosphere function and host interaction.
Pseudomonas fluorescens F113 is a plant growth-promoting rhizobacterium (PGPR) isolated from the sugar-beet rhizosphere. This bacterium has been extensively studied as a model strain for genetic regulation of secondary metabolite production in P. fluorescens, as a candidate biocontrol agent against phytopathogens, and as a heterologous host for expression of genes with biotechnological application. The F113 genome sequence and annotation has been recently reported. Comparative analysis of 50 genome sequences of strains belonging to the P. fluorescens group has revealed the existence of five distinct subgroups. F113 belongs to subgroup I, which is mostly composed of strains classified as P. brassicacearum. The core genome of these five strains is highly conserved and represents approximately 76% of the protein-coding genes in any given genome. Despite this strong conservation, F113 also contains a large number of unique protein-coding genes that encode traits potentially involved in the rhizocompetence of this strain. These features include protein coding genes required for denitrification, diterpenoids catabolism, motility and chemotaxis, protein secretion and production of antimicrobial compounds and insect toxins. The genome of P. fluorescens F113 is composed of numerous protein-coding genes, not usually found together in previously sequenced genomes, which are potentially decisive during the colonisation of the rhizosphere and/or interaction with other soil organisms. This includes genes encoding proteins involved in the production of a second flagellar apparatus, the use of abietic acid as a growth substrate, the complete denitrification pathway, the possible production of a macrolide antibiotic and the assembly of multiple protein secretion systems.


[Effect of chemoimmunotherapy on the sensitivity of T-lymphocytes to theophylline in lymphoma].
The state of the T-cellular immunity system was studied in mice with experimental lymphoma during the treatment with cyclophosphamide and active specific immunotherapy with ConA-modified syngeneic tumor cells. The advantages of the combined method of treatment and the high informative value of the test of E-rosette-formation sensitivity to theophylline in the evaluation of the therapeutic effect have been shown.


Systematic Identification of Methyl Jasmonate-Responsive Long Noncoding RNAs and Their Nearby Coding Genes Unveils Their Potential Defence Roles in Tobacco BY-2 Cells.
Long noncoding RNAs (lncRNAs) are distributed in various species and play critical roles in plant growth, development, and defence against stimuli. However, the lncRNA response to methyl jasmonate (MeJA) treatment has not been well characterized in Nicotiana tabacum Bright Yellow-2 (BY-2) cells, and their roles in plant defence remain elusive. Here, 7848 reliably expressed lncRNAs were identified in BY-2 cells, of which 629 differentially expressed (DE) lncRNAs were characterized as MeJA-responsive lncRNAs. The lncRNAs in BY-2 cells had a strong genus specificity in Nicotiana. The combined analysis of the cis-regulated lncRNAs and their target genes revealed the potential up- and downregulated target genes that are responsible for different biological functions and metabolic patterns. In addition, some lncRNAs for response-associated target genes might be involved in plant defence and stress resistance via their MeJA- and defence-related cis-regulatory elements. Moreover, some MeJA-responsive lncRNA target genes were related to quinolinate phosphoribosyltransferase, lipoxygenases, and endopeptidase inhibitors, which may contribute to nicotine synthesis and disease and insect resistance, indicating that MeJA-responsive lncRNAs regulate nicotine biosynthesis and disease resistance by regulating their potential target genes in BY-2 cells. Therefore, our results provide more targets for genetically engineering the nicotine content and plant defence in tobacco plants.


[Procoagulant properties of beta/gamma-thrombin].
If beta/gamma-thrombin interacted with blood plasma in vitro, shortening of recalcification period as well as partial thromboplastin time were observed in blood plasma, which were not related to low amount of alpha-thrombin in the preparation. Intensity of the procoagulant effect depended on the enzyme concentration. Presence of an excess of phospholipids did not inhibit this effect suggesting that the latter did not involve the thrombocytic factor 3 liberation. Factor V was shown to be activated by beta/gamma-thrombin in blood plasma, the rate of which depends on the enzyme concentration; the activation was not due to low content of alpha-thrombin in the preparation. Activation of factor V was only responsible for the procoagulant activity of beta/gamma-thrombin as shown by time-analysis of the reaction and by the enzyme concentrations used. Interaction of beta-gamma-thrombin with blood plasma led also to a gradual decrease in activity of factor VIII and did not affect the factor VII activity. The data obtained showed that beta/gamma-thrombin, deprived of ability to coagulate fibrinogen, maintained its activity towards the other factors of blood coagulation, suggesting the presence of independent haemostatic function in the enzyme.


A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma-A Proof of Antigen Discovery Feasibility in Three Patients.
Despite the promising therapeutic effects of immune checkpoint blockade (ICB), most patients with solid tumors treated with anti-PD-1/PD-L1 monotherapy do not achieve objective responses, with most tumor regressions being partial rather than complete. It is hypothesized that the absence of pre-existing antitumor immunity and/or the presence of additional tumor immune suppressive factors at the tumor microenvironment are responsible for such therapeutic failures. It is therefore clear that in order to fully exploit the potential of PD-1 blockade therapy, antitumor immune response should be amplified, while tumor immune suppression should be further attenuated. Cancer vaccines may prime patients for treatments with ICB by inducing effective anti-tumor immunity, especially in patients lacking tumor-infiltrating T-cells. These "non-inflamed" non-permissive tumors that are resistant to ICB could be rendered sensitive and transformed into "inflamed" tumor by vaccination. In this article we describe a clinical study where we use pancreatic cancer as a model, and we hypothesize that effective vaccination in pancreatic cancer patients, along with interventions that can reprogram important immunosuppressive factors in the tumor microenvironment, can enhance tumor immune recognition, thus enhancing response to PD-1/PD-L1 blockade. We incorporate into the schedule of standard of care (SOC) chemotherapy adjuvant setting a vaccine platform comprised of autologous dendritic cells loaded with personalized neoantigen peptides (PEP-DC) identified through our own proteo-genomics antigen discovery pipeline. Furthermore, we add nivolumab, an antibody against PD-1, to boost and maintain the vaccine's effect. We also demonstrate the feasibility of identifying personalized neoantigens in three pancreatic ductal adenocarcinoma (PDAC) patients, and we describe their optimal incorporation into long peptides for manufacturing into vaccine products. We finally discuss the advantages as well as the scientific and logistic challenges of such an exploratory vaccine clinical trial, and we highlight its novelty.


Sparse Coding on Symmetric Positive Definite Manifolds Using Bregman Divergences.
This paper introduces sparse coding and dictionary learning for symmetric positive definite (SPD) matrices, which are often used in machine learning, computer vision, and related areas. Unlike traditional sparse coding schemes that work in vector spaces, in this paper, we discuss how SPD matrices can be described by sparse combination of dictionary atoms, where the atoms are also SPD matrices. We propose to seek sparse coding by embedding the space of SPD matrices into the Hilbert spaces through two types of the Bregman matrix divergences. This not only leads to an efficient way of performing sparse coding but also an online and iterative scheme for dictionary learning. We apply the proposed methods to several computer vision tasks where images are represented by region covariance matrices. Our proposed algorithms outperform state-of-the-art methods on a wide range of classification tasks, including face recognition, action recognition, material classification, and texture categorization.


Role of purine biosynthetic intermediates in response to folate stress in Escherichia coli.
Folic acid plays a central role in anabolic metabolism by supplying single-carbon units at varied levels of oxidation for both nucleotide and amino acid biosyntheses. It has been proposed that 5-amino-4-imidazole carboxamide riboside 5'-triphosphate (ZTP), an intermediate in de novo purine biosynthesis, serves as a signal of cellular folate stress and mediates a physiologically beneficial response to folate stress in Salmonella typhimurium (B. R. Bochner, and B. N. Ames, Cell 29:929-937, 1982). We examined the physiological response of Escherichia coli to folate stress induced by the drugs psicofuranine, trimethoprim, and sodium sulfathiazole or by p-aminobenzoic acid (pABA) starvation. Analysis of nucleotide pools showed that psicofuranine or trimethoprim treatment of a prototrophic strain or growth of a pABA auxotroph on limiting pABA induced the production of the nucleotide ZTP, as previously observed in S. typhimurium by Bochner and Ames. Accumulation of ZTP and its precursor 5-amino-4-imidazole carboxamide riboside 5'-monophosphate (ZMP) did not correlate well with folate stress in E. coli, as measured by determination of the folate/protein ratios of extracts of treated cells. Treatment of cells with psicofuranine caused a marked accumulation of 5-amino-4-imidazole carboxamide ribonucleotides (Z-ribonucleotides) but a statistically insignificant drop in the folate/protein ratio of cell extracts. Sodium sulfathiazole treatment at a drug concentration that led to a threefold drop in the growth rate and in the folate/protein ratio of treated cells led to little accumulation of Z-ribonucleotides in E. coli A purF his+ strain which produces ZTP and ZMP when treated with trimethoprim was constructed. In this strain, histidine represses the synthesis of both ZMP and ZTP. Treatment of cells of this strain with trimethoprim resulted in a decrease in the folate/protein ratio of cell extracts, but a blockade of Z-ribonucleotide accumulation did not affect the extent of folate depletion seen in treated cells and had only a small effect on the resistance of this strain to growth inhibition by trimethoprim. The patterns of protein expression induced by treatment of this strain with trimethoprim or psicofuranine were examined by two-dimensional electrophoretic resolution of the total cellular proteins. No differences in protein expression were seen when the treatment were performed in media containing or lacking histidine. These studies failed to provide evidence in E. coli for a folate stress regulon controlled by ZTP.


Pest management in future climates: Warming reduces physical weed management effectiveness.
Climate change alters many aspects of weed performance and may also alter the effectiveness of management practices to control pests. Despite this concern, entire categories of widely used management practices, such as physical control, remain understudied in this context. We conducted a field experiment growing the invasive pest musk thistle (Carduus nutans) at ambient and experimentally elevated temperatures. We tested mowing management strategies that varied in the timing of a single mowing event relative to thistles' stem elongation phenology and compared these with an unmowed control. Results from this experiment informed demographic models to project population growth rates for different warming/mowing scenarios. Compared to plants grown under ambient conditions, warmed thistles were more likely to survive the same mowing treatment, flowered earlier in the season, grew to taller heights, and produced more flowering capitula. Proportional reductions in plant height and capitulum production caused by mowing were smaller under warming. Warming did not change the relative ranking of mowing treatments; mowing late in the growing season (2 weeks after individuals first reached a height of 40 cm) was most effective at ambient temperatures and under warming. Warming caused significant increases in projected local population growth rate for all mowing treatments. For invasive musk thistle, warmed individuals outperformed individuals grown at ambient temperatures across all the mowing treatments we considered. Our results suggest that to achieve outcomes comparable to those attainable at today's temperatures, farmers will need to apply supplemental management, possibly including additional mowing effort or alternative practices such as chemical control. We recommend that scientists test management practices under experimental warming, where possible, and that managers monitor ongoing management to identify changes in effectiveness. Information about changes in managed weeds' mortality, fecundity, and phenology can then be used to make informed decisions in future climates.


The level of manganese superoxide dismutase content is an independent prognostic factor for glioblastoma. Biological mechanisms and clinical implications.
We address the issue of the role of manganese superoxide dismutase in tumorigenesis by studying a relatively homogeneous group of tumours for the correlation between amount of this anti-oxidant enzyme and prognosis. The clinical outcome of 30 patients affected by glioblastomas whose manganese superoxide dismutase content had been established at the time of first diagnosis is compared. When the survival of patients is stratified according to manganese superoxide dismutase level in the tumour, a link of these levels and prognosis can be observed. Patients with high levels of manganese superoxide dismutase show a median survival time of 6.11 months, while patients whose tumours display a low amount of MnSOD have a median survival time of 12.17 months. To assess the upstream mechanisms that sustain the increase in manganese superoxide dismutase content in brain neuroepithelial tumours, we also studied the expression of p53 in a series of 17 astrocytomas of various grading. In all tested astrocytomas, high manganese superoxide dismutase content is associated with cytoplasmic accumulation of p53. Thus glioblastomas can be divided into two distinct groups on the basis of their content of manganese superoxide dismutase, having 'better' or 'worse' prognosis, respectively. The use of this protein as a marker may help to define therapeutic strategies in the clinical management of glioblastoma.


A randomized controlled feasibility trial exploring partnered ballroom dancing for people with Parkinson's disease.
To determine the feasibility of a Dance Centre delivering a programme of mixed dances to people with Parkinson's and identify suitable outcomes for a future definitive trial. A two-group randomized controlled feasibility trial. People with Parkinson's were randomized to a control or experimental group (ratio 15:35), alongside usual care. In addition, participants in the experimental group danced with a partner for one hour, twice-a-week for 10 weeks; professional dance teachers led the classes and field-notes were kept. Control-group participants were given dance class vouchers at the end of the study. Blinded assessments of balance, mobility and function were completed in the home. Qualitative interviews were conducted with a subsample to explore the acceptability of dance. A total of 51 people with Parkinson's (25 male) with Hoehn and Yahr scores of 1-3 and mean age of 71 years (range 49-85 years), were recruited to the study. Dance partners were of similar age (mean 68, range 56-91 years). Feasibility findings focused on recruitment (target achieved); retention (five people dropped out of dancing); outcome measures (three measures were considered feasible, changes were recommended). Proposed sample size for a Phase III trial, based on the 6-minute walk test at six months was 220. Participants described dance as extremely enjoyable and the instructors were skilled in instilling confidence and motivation. The main organizational challenges for a future trial were transport and identifying suitable dance partners. We have demonstrated the feasibility of conducting the study through a Dance Centre and recommend a Phase III trial.


[The movement for reassessing education and research in nursing history].
The thematic focus of this work is a call for reconsidering Education and Research on Nursing History (NH). Such movement is deemed a late manifestation in a process of improvement in Nursing knowledge, mediated by the development of stricto sensu Postgraduate programs, by the end of the 20th century, when a wakening of the Nursing area was seen due to a need to search for balance between technical and scientific competence and the ability for social criticism and professional self-assessment. An analysis of the possibilities and limitations of education and research in NH is presented, as well as its contribution to the advancement of the profession, and implications from understanding NH as an interdisciplinary field are discussed.


The novel progesterone receptor antagonists RTI 3021-012 and RTI 3021-022 exhibit complex glucocorticoid receptor antagonist activities: implications for the development of dissociated antiprogestins.
We have identified two novel compounds (RTI 3021-012 and RTI 3021-022) that demonstrate similar affinities for human progesterone receptor (PR) and display equivalent antiprogestenic activity. As with most antiprogestins, such as RU486, RTI 3021-012, and RTI 3021-022 also bind to the glucocorticoid receptor (GR) with high affinity. Unexpectedly, when compared with RU486, the RTI antagonists manifest significantly less GR antagonist activity. This finding indicates that, with respect to antiglucocorticoid function, receptor binding affinity is not a good predictor of biological activity. We have determined that the lack of a clear correlation between the GR binding affinity of the RTI compounds and their antagonist activity reflects the unique manner in which they modulate GR signaling. Previously, we proposed a two step "active inhibition" model to explain steroid receptor antagonism: 1) competitive inhibition of agonist binding; and 2) competition of the antagonist bound receptor with that activated by agonists for DNA response elements within target gene promoters. Accordingly, we observed that RU486, RTI 3021-012, and RTI 3021-022, when assayed for PR antagonist activity, accomplished both of these steps. Thus, all three compounds are "active antagonists" of PR function. When assayed on GR, however, RU486 alone functioned as an active antagonist. RTI 3021-012 and RTI 3021-022, on the other hand, functioned solely as "competitive antagonists" since they were capable of high affinity GR binding, but the resulting ligand receptor complex was unable to bind DNA. These results have important pharmaceutical implications supporting the use of mechanism based approaches to identify nuclear receptor modulators. Of equal importance, RTI 3021-012 and RTI 3021-022 are two new antiprogestins that may have clinical utility and are likely to be useful as research reagents with which to separate the effects of antiprogestins and antiglucocorticoids in physiological systems.


Comparison of Early T-Cell Precursor and Non-ETP Subtypes Among 122 Chinese Adults With Acute Lymphoblastic Leukemia.
Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy and significantly linked to poor outcomes. Early T-cell precursor (ETP) leukemia is a unique subtype of T-ALL. The aim of this study is to compare the differences between ETP and non-ETP ALLs in China. Methods: We retrospectively analyzed the records of 122 adult T-ALL patients diagnosed and treated at our center between January 2014 and June 2019. All the patients enrolled were categorized into ETP and non-ETP ALL by immunophenotype, and further statistical analyses about clinical data and prognostic factors were performed. Results: Among the 122 cases, the male-to-female ratio was 2.8:1, and the median age is 29 (range, 16-82) years. Except for 10 patients with insufficient immunophenotyping results, 47.3% (53/112) are ETP and 52.7% (59/112) are non-ETP. Compared with non-ETP patients, ETP-ALL patients had lower white blood cell counts and lactate dehydrogenase levels, while they were older and had higher platelet counts and fibrinogen levels (all p < 0.05). Complete remission (CR) was achieved in 68.0% (83/122) of patients, 64.2 and 76.3% in ETP and non-ETP, respectively (p = 0.160). In total, 44.6% (37/83) of patients relapsed. Allogeneic stem cell transplantation (allo-SCT) was successfully performed in 36.1% (44/122) of patients, of which 79.5% (35/44) were in CR1. With a median follow-up of 9.1 (range, 0.5-70.3) months, the estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates for the cohort were 38.0 ± 5.1 and 39.1 ± 6.3%, respectively. In the ETP group, the 2-year OS rate was 40.7 ± 8.2% and the RFS rate was 47.2 ± 10.7%, while in the non-ETP group, the 2-year OS rate was 37.9 ± 7.0% and the RFS rate was 39.2 ± 8.3% (both p > 0.05). In the landmark analysis of CR1 patients who had a survival of more than 6 months, the allo-SCT group had significantly better survival outcomes than the chemotherapy group, and the 2-year OS rates and RFS rates were 80.1 ± 7.3 vs. 28.4 ± 8.4% and 68.9 ± 8.8 vs. 12.8 ± 7.2%, respectively (both p < 0.0001). A multivariate analysis suggests that allo-SCT acts as an independent prognostic factor for both OS and RFS. Conclusions: Our results revealed that ETP accounted for a high proportion of T-ALL in Chinese. There are no CR rates and prognosis differences between ETP and non-ETP. Allo-SCT in CR1 can significantly improve patients' survival.


Treatment of congenital erythropoietic porphyria in children by allogeneic stem cell transplantation: a case report and review of the literature.
Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder of porphyrin metabolism in which the genetic defect is the deficiency of uroporphyrinogen III cosynthase (UIIIC). Deficiency of this enzyme results in an accumulation of high amounts of uroporphyrin I in all tissues leading to hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite photosensitivity and mutilating skin lesions. We describe the case of a 23-month-old boy who was cured of his CEP by a matched-sibling allogeneic bone marrow transplant, and review the published clinical experience regarding transplantation in this disease. He is alive and disease-free 15 months post transplant. All of his disease manifestations except for the erythrodontia have resolved. His UIIIC level and stool and erythrocyte porphyrin metabolites have almost completely corrected. He is the sixth child reported to be cured of this disease by stem cell transplantation, five cases being long-term survivors. If patients with this disease have an HLA-matched sibling, then stem cell transplantation should be strongly considered because this is currently the only known curative therapy.


Expression of NHERF-1, NHERF-2, PDGFR-alpha, and PDGFR-beta in normal human kidneys and in renal transplant rejection.
Sodium-hydrogen exchanger regulatory factor-1 and -2 (NHERF-1 and NHERF-2) are adaptor proteins that regulate renal electrolyte transport and interact with the platelet-derived growth factor receptors (PDGFR). The distribution of the NHERF proteins and PDGFR was studied in normal human kidneys and in renal transplant rejection using immunocytochemistry. In normal kidneys, NHERF-1 was detected in proximal tubules. NHERF-2 was detected in glomeruli, peritubular capillaries, and collecting duct principal cells. NHERF-2 was also weakly detected in the proximal tubule. PDGFR-beta was detected in glomeruli but not in tubules while PDGFR-alpha was detected in renal tubules and minimally in glomeruli. Acute and chronic transplant rejection was associated with increased expression of PDGFR-alpha in tubules and expression in the glomeruli. PDGFR-beta expression in the glomeruli was increased in transplant rejection and became detectable in tubules. Expression of NHERF-1 and NHERF-2 was not different in the patient groups. These results indicate that in contrast to the rat, both NHERF isoforms are detected in the human proximal tubule. In renal transplant rejection, there is increased expression of both PDGFR subtypes consistent with a role for PDGF in injury or repair.


Assessment of risk of PCDD/Fs and dioxin-like PCBs in marine and freshwater fish in Pearl River Delta, China.
Fish consumption is known to be beneficial to human health. However since the age of industrialization, the released/disposed chemical pollutants into water systems make fish a source of various environmental toxicants to humans. In oceanic cities with heavy industrial activities, fish products contribute the greatest proportion of exposure to pollutants. In this study, risks and potential effects of dioxins to health of coastal populations in the Pearl River Delta were assessed. Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) were measured in common fish species purchased at local markets. Concentrations of total dioxins in fish ranged from 0.481 to 9.05 pg TEQ/g wet weight were similar to the lesser concentrations reported for fish from other countries. The greatest concentrations of dioxins were measured in mandarin fish, a carnivorous freshwater fish. Exposure of murine primary leydig and ovarian cells to 2,3,7,8-tetrachlorinated dibenzo-p-dioxins (2,3,7,8-TCDD) reduced the synthesis of progesterone, testosterone and/or estrogen. The reductions were probably via inhibitory effects on the expression of the steroidogenic enzymes, steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc). Based on these reproductive parameters, the concentrations of dioxins and dioxin-like residues represent a moderate health risk due to consumption of fish.


Percutaneous Endoscopic Gastrostomy in Ile-Ife, Nigeria:An Initial Report.
Protein-energy malnutrition is a common problem in critically ill patient and it is a major cause of accelerated morbidity and mortality in this group of patients. Recent dramatic advances in both enteral and parenteral nutritional support have ensured that most of these critically ill patients are adequately nutritionally supported. Unfortunately, most of these advancements in nutritional supports are far from the reach of most patients in developing countries. In this report, we highlighted the indications, success, challenges of the use of percutaneous endoscopic gastrostomy (PEG) in Nigeria patients. All cases of PEG performed at the Endoscopy Unit of Obafemi Awolowo University Teaching Hospitals complex, Ile-Ife, Osun State from January 2011 and June 2012 were recruited into the study. The data obtained included the sociodemographic parameters, indication and duration of the procedure, complications, and follow up. During the 18 months study period 645 upper gastrointestinal endoscopic procedures were performed. Majority [601(93.2%)] of the cases were for diagnostic purposes. Six (0.9%) cases of PEG were performed. Most (5 of 6) of the patients had central nervous system impairment while only one had severe chronic facial infection with naso-oral fistula. The median age of patients was 60.5 years. The entire procedure including endoscopy lasted an average of 25 minutes with a range of 12-35 minutes. Only one case had peristoma infection which resolved with antibiotics and repeated dressing with povidone iodine. There was no episode of aspiration pneumonitis or procedure related mortality. The average follow up was 6 months with variable weight gain during the follow up period. PEG is a simple, cost effective and safe method to rehabilitate nutritionally all chronically ill patients in less developed countries such as Nigeria. The need to increase awareness and acceptability of PEG among physicians managing such patients and the society cannot be overemphasized.


Added value of advanced workup after the first seizure: A 7-year cohort study.
This study was undertaken to establish whether advanced workup including long-term electroencephalography (LT-EEG) and brain magnetic resonance imaging (MRI) provides an additional yield for the diagnosis of new onset epilepsy (NOE) in patients presenting with a first seizure event (FSE). In this population-based study, all adult (≥16 years) patients presenting with FSE in the emergency department (ED) between March 1, 2010 and March 1, 2017 were assessed. Patients with obvious nonepileptic or acute symptomatic seizures were excluded. Routine EEG, LT-EEG, brain computed tomography (CT), and brain MRI were performed as part of the initial workup. These examinations' sensitivity and specificity were calculated on the basis of the final diagnosis after 2 years, along with the added value of advanced workup (MRI and LT-EEG) over routine workup (routine EEG and CT). Of the 1010 patients presenting with FSE in the ED, a definite diagnosis of NOE was obtained for 501 patients (49.6%). Sensitivity of LT-EEG was higher than that of routine EEG (54.39% vs. 25.5%, p < .001). Similarly, sensitivity of MRI was higher than that of CT (67.98% vs. 54.72%, p = .009). Brain MRI showed epileptogenic lesions in an additional 32% compared to brain CT. If only MRI and LT-EEG were considered, five would have been incorrectly diagnosed as nonepileptic (5/100, 5%) compared to patients with routine EEG and MRI (25/100, 25%, p = .0001). In patients with all four examinations, advanced workup provided an overall additional yield of 50% compared to routine workup. Our results demonstrate the remarkable added value of the advanced workup launched already in the ED for the diagnosis of NOE versus nonepileptic causes of seizure mimickers. Our findings suggest the benefit of first-seizure tracks or even units with overnight EEG, similar to stroke units, activated upon admission in the ED.