Six-Year Nitrogen-Water Interaction Shifts the Frequency Distribution and Size Inequality of the First-Order Roots of Fraxinus mandschurica in a Mixed Mature Pinus koraiensis Forest.
The variation in fine root traits in terms of size inequality at the individual root level can be identified as a strategy for adapting to the drastic changes in soil water and nutrient availabilities. The Gini and Lorenz asymmetry coefficients have been applied to describe the overall degree of size inequality, which, however, are neglected when conventional statistical means are calculated. Here, we used the Gini coefficient, Lorenz asymmetry coefficient and statistical mean in an investigation of Fraxinus mandschurica roots in a mixed mature Pinus koraiensis forest on Changbai Mountain, China. We analyzed 967 individual roots to determine the responses of length, diameter and area of the first-order roots and of branching intensity to 6 years of nitrogen addition (N), rainfall reduction (W) and their combination (NW). We found that first-order roots had a significantly greater average length and area but had smaller Gini coefficients in NW plots compared to in control plots (CK). Furthermore, the relationship between first-order root length and branching intensity was negative in CK, N, and W plots but positive in NW plots. The Lorenz asymmetry coefficient was >1 for the first-order root diameter in NW and W plots as well as for branching intensity in N plots. The bimodal frequency distribution of the first-order root length in NW plots differed clearly from the unimodal one in CK, N, and W plots. These results demonstrate that not only the mean but also the variation and the distribution mode of the first-order roots of F. mandschurica respond to soil nitrogen and water availability. The changes in size inequality of the first-order root traits suggest that Gini and Lorenz asymmetry coefficients can serve as informative parameters in ecological investigations of roots to improve our ability to predict how trees will respond to a changing climate at the individual root level.


Liddle's syndrome: A case report.
Liddle's syndrome or pseudoaldosteronism is a rare autosomal dominant disease mimicking primary hyperaldosteronism, characterized by early-onset hypertension, hypokalemia and hypoaldosteronism, caused by excessive salt and water reabsorption in the distal nephron. As of 2008, there are <30 pedigrees or isolated cases that have been reported worldwide. We present an isolated case of a Liddle's syndrome in a 48-year-old female. A 48-year-old female presented to the clinic with palpitation and a three to four-year history of low potassium level and hypertension. She was initially treated with a high potassium diet and potassium supplements. Her cardiac work-up including echocardiography, stress test and Holter monitoring were all negative. After a few months, she was admitted to the hospital with an acute hypertensive episode and hypokalemia. On evaluation, she was found to have low renin and aldosterone levels. Liddle's syndrome was considered with the clinical picture of hypokalemia, hypertension and low renin/ aldosterone level. The patient was successfully treated with a high potassium diet, triamterene and atenolol. Liddle's syndrome should be considered as the differential diagnosis in patients presenting with the clinical picture of hypokalemia, hypertension and low renin/aldosterone level.


Expression of Carbonic Anhydrase I in Motor Neurons and Alterations in ALS.
Carbonic anhydrase I (CA1) is the cytosolic isoform of mammalian α-CA family members which are responsible for maintaining pH homeostasis in the physiology and pathology of organisms. A subset of CA isoforms are known to be expressed and function in the central nervous system (CNS). CA1 has not been extensively characterized in the CNS. In this study, we demonstrate that CA1 is expressed in the motor neurons in human spinal cord. Unexpectedly, a subpopulation of CA1 appears to be associated with endoplasmic reticulum (ER) membranes. In addition, the membrane-associated CA1s are preferentially upregulated in amyotrophic lateral sclerosis (ALS) and exhibit altered distribution in motor neurons. Furthermore, long-term expression of CA1 in mammalian cells activates apoptosis. Our results suggest a previously unknown role for CA1 function in the CNS and its potential involvement in motor neuron degeneration in ALS.


A general modeling and visualization tool for comparing different members of a group: application to studying tau-mediated regulation of microtubule dynamics.
Innumerable biological investigations require comparing collections of molecules, cells or organisms to one another with respect to one or more of their properties. Almost all of these comparisons are performed manually, which can be susceptible to inadvertent bias as well as miss subtle effects. The development and application of computer-assisted analytical and interpretive tools could help address these issues and thereby dramatically improve these investigations. We have developed novel computer-assisted analytical and interpretive tools and applied them to recent studies examining the ability of 3-repeat and 4-repeat tau to regulate the dynamic behavior of microtubules in vitro. More specifically, we have developed an automated and objective method to define growth, shortening and attenuation events from real time videos of dynamic microtubules, and demonstrated its validity by comparing it to manually assessed data. Additionally, we have used the same data to develop a general strategy of building different models of interest, computing appropriate dissimilarity functions to compare them, and embedding them on a two-dimensional plot for visualization and easy comparison. Application of these methods to assess microtubule growth rates and growth rate distributions established the validity of the embedding procedure and revealed non-linearity in the relationship between the tau:tubulin molar ratio and growth rate distribution. This work addresses the need of the biological community for rigorously quantitative and generally applicable computational tools for comparative studies. The two-dimensional embedding method retains the inherent structure of the data, and yet markedly simplifies comparison between models and parameters of different samples. Most notably, even in cases where numerous parameters exist by which to compare the different samples, our embedding procedure provides a generally applicable computational strategy to detect subtle relationships between different molecules or conditions that might otherwise escape manual analyses.


Plasma and urine profiles of Delta9-tetrahydrocannabinol and its metabolites 11-hydroxy-Delta9-tetrahydrocannabinol and 11-nor-9-carboxy-Delta9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes.
Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Delta(9)-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 +/- 1,111 ng/mL), THC (3 +/- 8 ng/mL) and THC-OH (51 +/- 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes.


Surface-engineered nanomaterials as X-ray absorbing adjuvant agents for Auger-mediated chemo-radiation.
We report a prototype approach to formulate gold nanoparticle-based X-ray absorbing agents through surface-engineering of a cisplatin pharmacophore with modified polyacrylate. The resulting agents exhibit both chemo-therapeutic potency to cancer cells and Auger-mediated secondary electron emission, showing great potential to improve the therapeutic efficacy of chemo-radiation.


Membrane protein Crry maintains homeostasis of the complement system.
Complement activation is tightly regulated to avoid excessive inflammatory and immune responses. Crry(-/-) is an embryonic lethal phenotype secondary to the maternal complement alternative pathway (AP) attacking a placenta deficient in this inhibitor. In this study, we demonstrate that Crry(-/-) mice could be rescued on a partial as well as on a complete factor B (fB)- or C3-deficient maternal background. The C3 and fB protein concentrations in Crry(-/-)C3(+/-) and Crry(-/-)fB(+/-) mice were substantially reduced for gene dosage secondary to enhanced AP turnover. Based on these observations, a breeding strategy featuring reduced maternal AP-activating capacity rescued the lethal phenotype. It led to a novel, stable line of Crry SKO mice carrying normal alleles for C3 and fB. Crry SKO mice also had accelerated C3 and fB turnover and therefore reduced AP- activating potential. These instructive results represent an example of a membrane regulatory protein being responsible for homeostasis of the complement system. They imply that there is constant turnover on cells of the AP pathway which functions as an immune surveillance system for pathogens and altered self.


Effectiveness and safety of internal rectilinear biphasic versus monophasic defibrillation in patients undergoing cardiac surgery.
Recently it has been shown that biphasic external shocks are more effective in the treatment of ventricular fibrillation (VF) compared with monophasic external shocks in terms of number of defibrillation attempts and maximal energy used for termination of VF. Biphasic defibrillators apply different biphasic impulse forms, depending on technology. To the authors' knowledge, there are no existing data concerning the effects of rectilinear biphasic internal shocks in patients undergoing cardiac surgery. The purpose of this study was to compare monophasic with rectilinear biphasic internal shock waveforms for termination of VF in patients undergoing cardiac surgery. One hundred thirty-four patients scheduled for elective cardiac surgery were prospectively randomized either to monophasic (group A) or biphasic (group B) internal defibrillation. Defibrillation was started with 7 J and increased stepwise to 30 J in each group until successful termination of VF after aortic declamping. The number of defibrillations, as well as the cumulative and maximal energy for termination of VF, were determined. Preoperatively, intraoperatively, and postoperatively troponin T, total creatine phosphokinase (CPK), and CPK- MB isoenzymes were measured. In 64 patients (47%) VF occurred. The groups consisted of 32 patients each. The number of defibrillations (1.3 +/- 0.6 v 1.9+/- 1.2; p = 0.013), maximal energy per patient (7.9 +/- 2.5 v 11.6 +/- 7.32; p = 0.006), and cumulative energy (10.1 +/-6.1 v 21.3 +/- 24.1; p = 0.016) for successful termination of VF were significantly reduced in group B. Troponin T, CPK, and CPK-MB did not differ between groups. Results of this study indicate that rectilinear biphasic internal defibrillation is more effective in the treatment of VF during cardiac surgery than is monophasic defibrillation. However, no significant difference in myocardial damage could be detected between groups.


Important role of TNF-alpha in inhibitory effects of Radix Sophorae Flavescentis extract on vascular restenosis in a rat carotid model of balloon dilatation injury.
The aim of this study was to determine the molecular mechanism underlying the inhibition of vascular restenosis by Radix Sophorae Flavescentis (RSF) extract after balloon dilatation injury. In a rat carotid model of balloon dilatation injury, the RSF extract showed a significant inhibitory effect on vascular restenosis. Immunohistochemistry showed that the expression of tumor necrosis factor-alpha (TNF-alpha) in the vascular focus was markedly reduced upon treatment with the RSF extract, whereas the expression of proliferating cell nuclear antigens (PCNA) was mostly unaffected. Colorimetric assays of methylene blue incorporation demonstrated that the proliferation of cultured vascular smooth muscle cells (VSMCs) was not inhibited with serum from rats treated with RSF extract. However, the expression of TNF-alpha in cultured VSMCs was significantly downregulated by serum from rats treated with RSF extract. These results suggested that RSF extract has an inhibitory effect on vascular restenosis after balloon dilatation injury which might be, in part, attributable to its inhibition of TNF-alpha expression.


Phosphorylated neurofilament heavy chain: a potential diagnostic biomarker in amyotrophic lateral sclerosis.
Neuroaxonal damage is a feature of various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Phosphorylated neurofilament heavy chain (pNfH) is a cytoskeletal structural protein released as a result of axonal damage into the cerebrospinal fluid (CSF), and subsequently into the blood. Due to high specificity for neuronal cell damage, pNfH is advantageous over other biomarkers, for ALS disease identification. Here, we review the structure and function of neurofilaments and their role in detection of various neurodegenerative conditions. In addition, a retrospective meta-analysis was performed to depict the significance of pNfH as a valuable diagnostic and prognostic biomarker in ALS.


Zwischen Himmel und Hölle: Erfahrungen von Eltern mit einem kritisch kranken Kind mit extrakorporaler Membranoxygenierung (ECMO) - Eine qualitative-explorative Studie mit Paarinterviews.
Between Heaven and Hell: Experiences of parents with a critically ill child with extracorporeal membrane oxygenation (ECMO) - A qualitative-explorative study with couple interviews Abstract. Background: It is a traumatic experience for parents when their child's severe illness necessitates a period of intensive care. This situation becomes even more challenging for parents if a highly technical therapy such as extracorporeal membrane oxygenation (ECMO) in the Pediatric Intensive Care Unit is required. Aim: The study explores the experiences of parents of critically ill children undergoing ECMO therapy with the aim of better understanding their needs and identifying courses of action for healthcare professionals. Method: The qualitative-explorative study was based on interviews with six couples whose critically ill child is or has been receiving ECMO during the last year, which were used to examine their experiences. The analysis of six such interviews was performed using intensive paraphrasing and inductive coding. Results: The parents' situation can be best characterised as ambivalent with simultaneous feelings of hope and fear. They recognize the danger to their child's life, leading to intense feelings of helplessness with strong emotional reactions. It becomes apparent that there is too little fit between the emotional world of the parents and the action patterns of the health care professionals. Conclusions: The health care professionals thinking logic is based on professional criteria, such as the life threat and risks of ECMO, which ignores the emotional needs of the parents. For this reason, it is important to be more sensitive to the parents and to share positive little signs about their child' s state of health and ability to suffer with them.


Low dose amiodarone reduces tumor growth and angiogenesis.
Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug's harmful side effects.


[A long-term survival case of recurrent pancreatic vipoma with liver metastases treated by a combination of surgical resection and loco-regional therapies].
We report a case of recurrent pancreatic VIPoma with liver and peritoneal metastases who has been surviving over 7 years by a successful treatment with a combination of surgical resection and loco-regional therapies. A 59-year-old female underwent distal pancreatectomy for pancreatic endocrine tumor. Five years after pancreatectomy, she had a recurrence of liver and peritoneal metastases with the symptoms by hypersecretion of VIP, and she underwent hepatectomy and peritoneal tumor resection. Seven months later, multiple liver metastases appeared and were treated with transcatheter arterial chemoembolization (TACE). Additionally radiofrequency ablation( RFA) for remnant viable lesion was performed. Seven years and eight months after primary panceatectomy and two years and six months after resection of the liver and peritoneal recurrences, she is now disease-free with good quality of life. The progression of well-differentiated pancreatic neuroendocrine carcinoma is usually slow. It is potentially useful in controlling of liver metastases to combine the loco-regional therapy like TACE and RFA with surgical resection.


Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function.
Ectopic lipid accumulation is now known to be a mechanism that contributes to organ injury in the context of metabolic diseases. In muscle and liver, accumulation of lipids impairs insulin signaling. This hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, aging and lipodystrophy. Increasing data suggest that lipid accumulation in the kidneys could also contribute to the alteration of kidney function in the context of metabolic syndrome and obesity. Furthermore and more unexpectedly, animal models of kidney disease exhibit a decreased adiposity and ectopic lipid redistribution suggesting that kidney disease may be a state of lipodystrophy. However, whether this abnormal lipid partitioning during chronic kidney disease (CKD) may have any functional impact in these tissues needs to be investigated. Here, we provide a perspective by defining the problem and analyzing the possible causes and consequences. Further human studies are required to strengthen these observations, and provide novel therapeutic approaches.


Eating from the wild: Turumbu indigenous knowledge on noncultivated edible plants, Tshopo District, DRCongo.
Documenting and revalorizing the rapidly disappearing indigenous knowledge on wild edible plants is essential to promote health and preserve diversity. Focus group discussions were organized within three Turumbu villages to document wild foods known, availability, preparation methods, and uses. Preferences in taste and commercial, nutritional, and cultural value were discussed during participatory ranking exercises. Results show 85 species within 70 genera and 44 families. Fruits of Anonidium manni and Landolphia owariensis, and (unfolded) leaves of Megaphrynium macrostachyum and Talinum triangulare are most appreciated. Inventories and preference rankings should be completed with nutritional analyses and market studies to set priorities for participatory domestication.


TRPA1-Mediated Src Family Kinases Activity Facilitates Cortical Spreading Depression Susceptibility and Trigeminovascular System Sensitization.
Transient receptor potential ankyrin 1 (TRPA1) plays a role in migraine and is proposed as a promising target for migraine therapy. However, TRPA1-induced signaling in migraine pathogenesis is poorly understood. In this study, we explored the hypothesis that Src family kinases (SFKs) transmit TRPA1 signaling in regulating cortical spreading depression (CSD), calcitonin gene-related peptide (CGRP) release and neuroinflammation. CSD was monitored in mouse brain slices via intrinsic optical imaging, and in rats using electrophysiology. CGRP level and IL-1β gene expression in mouse trigeminal ganglia (TG) was detected using Enzyme-linked Immunosorbent Assay and Quantitative Polymerase Chain Reaction respectively. The results showed a SFKs activator, pYEEI (EPQY(PO3H2)EEEIPIYL), reversed the reduced cortical susceptibility to CSD by an anti-TRPA1 antibody in mouse brain slices. Additionally, the increased cytosolic phosphorylated SFKs at Y416 induced by CSD in rat ipsilateral cerebral cortices was attenuated by pretreatment of the anti-TRPA1 antibody perfused into contralateral ventricles. In mouse TG, a SFKs inhibitor, saracatinib, restored the CGRP release and IL-1β mRNA level increased by a TRPA1 activator, umbellulone. Moreover, umbellulone promoted SFKs phosphorylation, which was reduced by a PKA inhibitor, PKI (14-22) Amide. These data reveal a novel mechanism of migraine pathogenesis by which TRPA1 transmits signaling to SFKs via PKA facilitating CSD susceptibility and trigeminovascular system sensitization.


Diaries and calendars for migraine. A review.
Headache is one of the most common types of pain and, in the absence of biological markers, headache diagnosis depends only on information obtained from clinical interviews and physical and neurological examinations. Headache diaries make it possible to record prospectively the characteristics of every attack and the use of headache calendars is indicated for evaluating the time pattern of headache, identifying aggravating factors and evaluating the efficacy of preventive treatment. This may reduce the recall bias and increase accuracy in the description. The use of diagnostic headache diaries does have some limitations because the patient's general acceptance is still limited and some subjects are not able to fill in a diary. In this review, we considered diaries and calendars especially designed for migraine and, in particular, we aimed at: (i) determining what instruments are available in clinical practice for diagnosis and follow-up of treatments; and (ii) describing the tools that have been developed for research and their main applications in the headache field. In addition to the literature review, we added two paragraphs concerning the authors' experience of the use of diaries and calendars in headache centres and their proposals for future areas of research.


Hemodynamic impact of anastomosis size and angle in side-to-end arteriovenous fistulae: a computer analysis.
An arteriovenous fistula (AVF) is the first choice vascular access for hemodialysis. The AVF pathway can be seen as consisting of seven segments: proximal artery, distal artery, arterial collaterals, proximal vein, distal vein, venous collaterals, and the anastomosis. While most studies describe access complications without considering the impact of the anastomosis (7th segment), the present mathematical study investigated the hemodynamic impact of anastomosis size and angle on pressure drop and flow distribution. A side-to-end AVF model was developed, consisting of an anastomosis with a given cross-sectional area (substudy 1) and angle (substudy 2). Starting from two reference cases (one for each substudy) with fixed flow distribution, pressure drop over the anastomosis was calculated for an arterial inflow in the range 600 to 1200 mL/min. The same reference cases, subsequently with fixed pressure boundary conditions, were further used to assess flow distribution over the proximal vein and distal artery. Pressure drop decreased with a larger anastomosis cross-sectional area and an angle wider than 43 degrees , while it was almost stable for smaller angles. Although proximal arterial inflow increased for larger anastomosis areas, the overall flow distribution shifted almost totally to the proximal vein. When the anastomosis angle exceeded 58 degrees , the proximal arterial inflow was not sufficient to deliver enough flow, leading to distal arterial flow reversal. Despite the underestimation of the hemodynamic impact of the anastomosis size and angle in the literature, this study showed major influences on the pressure drop over the anastomosis and, with it, on flow distribution towards the arterial and venous outflow.


Assessment of Impact and Recovery Needs in Communities Affected by the Elk River Chemical Spill, West Virginia, April 2014.
In January 2014, 4-methylcyclohexanemethanol spilled into the Elk River near Charleston, West Virginia, contaminating the water supply for about 120 000 households. The West Virginia American Water Company (WVAWC) issued a "do not use" water order for 9 counties. After the order was lifted (10 days after the spill), the communities' use of public water systems, information sources, alternative sources of water, and perceived impact of the spill on households were unclear to public health officials. To assist in recovery efforts, the West Virginia Bureau for Public Health and the Centers for Disease Control and Prevention conducted a Community Assessment for Public Health Emergency Response (CASPER). We used the CASPER 2-stage cluster sampling design to select a representative sample of households to interview, and we conducted interviews in 171 households in April 2014. We used a weighted cluster analysis to generate population estimates in the sampling frame. Before the spill, 74.4% of households did not have a 3-day alternative water supply for each household member and pet. Although 83.6% of households obtained an alternative water source within 1 day of the "do not use" order, 37.4% of households reportedly used WVAWC water for any purpose. Nearly 3 months after the spill, 36.1% of households believed that their WVAWC water was safe, and 33.5% reported using their household water for drinking. CASPER results identified the need to focus on basic public health messaging and household preparedness efforts. Recommendations included (1) encouraging households to maintain a 3-day emergency water supply, (2) identifying additional alternative sources of water for future emergencies, and (3) increasing community education to address ongoing concerns about water.


Maintenance of cartilaginous gene expression on extracellular matrix derived from serially passaged chondrocytes during in vitro chondrocyte expansion.
The loss of cartilaginous phenotype during in vitro expansion culture of chondrocytes is a major barrier for the application of cartilage tissue engineering. The use of matrices mimicking the in vivo extracellular matrix (ECM) microenvironment is anticipated to be an efficient method to suppress chondrocyte phenotype loss. In this study, we developed several types of ECM derived from serially passaged chondrocytes for use as cell-culture substrata and compared their effects on chondrocyte functions. Primary bovine chondrocytes and serially passaged chondrocytes (at passages 2 and 6) were cultured on tissue-culture polystyrene. After culture, the cellular components were selectively removed from the ECM deposited by the cells. The remaining ECM proteins were used as cell-culture substrata. The composition of the deposited ECM depended on the culture stage of the serially passaged chondrocytes used for the ECM production. The deposited ECM supported the adhesion and proliferation of chondrocytes. The effects of the ECM on the chondrocyte dedifferentiation during in vitro passage culture differed dramatically depending on the phenotype of the chondrocytes used to produce the ECM. The primary chondrocyte-derived ECM delayed the chondrocyte dedifferentiation during in vitro passage culture and is a good candidate for chondrocyte subculture for tissue engineering.


The relationship between anti-endomysium antibodies and villous atrophy in coeliac disease using both monkey and human substrate.
Circulating antibodies offer a noninvasive diagnostic screening test in patients with coeliac disease with severe histopathological abnormalities. This study assesses for the first time the sensitivity and reliability of anti-endomysium in screening for coeliac disease in patients with milder forms of villous atrophy using human umbilical cord and monkey ileum. Serum from 124 adults and children > 2 years old including 33 patients with coeliac disease on a gluten-free diet and 91 patients referred to the laboratory for screening was studied. The presence of IgA-anti-gliadin (AGA) (ELISA) and IgA-anti-endomysium (EMA) was detected in the serum using monkey ileum and human umbilical cord (HUC) substrates. Patients with abnormal serology results or severe clinical complaints were invited to attend for a small-bowel biopsy. The prevalence of EMA detected on monkey ileum and HUC was compared with the histopathological features of coeliac disease at presentation. Fifty-three of the 91 patients screened for coeliac disease underwent a small intestinal biopsy. Twenty-three of the 91 patients suspected of having coeliac disease had coeliac disease. The EMA test was positive in 18 of 23 using both monkey ileum and HUC (sensitivity 78%). Partial villous atrophy (PVA) was seen in four of the five EMA-negative patients, and subtotal/total villous atrophy (SVA/TVA) was demonstrated in 18 of the 23 cases with positive EMA. Both substrates detected identical positive cases. There was an excellent concordance between EMA sensitivity evaluated on HUC and those on monkey ileum. One patient was EMA-negative on monkey ileum but positive on HUC and one patient who was EMA-positive on monkey ileum was EMA-negative on HUC. Only one of 33 coeliac disease patients on gluten-free diet for more than one year with persisting TVA had positive EMA. The rest of the cases had a negative EMA on both HUC and monkey ileum. A negative result for EMA in coeliac disease patients with a normal IgA value does not exclude the diagnosis of coeliac disease. A positive EMA is seen mostly in those coeliac disease patients with severe tissue damage (SVA/TVA). EMA has a low sensitivity in coeliac disease patients with PVA in spite of use of different substrates.


[Social participation processes, task-oriented participation and learning as antecedents of group cohesion. A longitudinal perspective].
The aim of this paper is to analyze the effect of changes in social participation and task- and learning-oriented processes on the development of cohesion (social and task-focused) in new groups. Cohesion has been considered one of the most important constructs in small groups, and its influence on team performance and efficacy has been highlighted. However, there are few papers that analyze the processes and the variables that precede the construct and that affect its evolution. Results of the longitudinal study show the importance of changes in participation processes on the development of task cohesion and social cohesion.


Effects of CPAP treatment on psychological status in patients with severe obstructive sleep apnoea.
The aim of this study was to evaluate the effects of nocturnal continuous positive airway pressure (CPAP) breathing on the emotional status and cognitive function in 20 patients with severe obstructive sleep apnoea (OSA) (mean +/- SD apnoea/hypopnoea index = 67 +/- 16, mean overnight arterial oxygen saturation = 83 +/- 10%). Psychological tests were performed before, after three, and after twelve months of CPAP treatment. At initial investigation, amongst cognitive functions, the most disturbed were concentration and recent memory. The majority of subjects demonstrated increased mental stress, depression, and anxiety. Anxiety correlated with AHI (r = 0.68). Mental stress correlated with AHI (r = 0.56) and deficiency of Stage 2 NREM sleep (r = -0.55). CPAP treatment resulted in significant improvement in cognitive function; concentration, recent verbal, visual and spatial memory were already seen at three months. No improvement in IQ and in emotional status after three months and one year of treatment was found. It is concluded that in patients with severe OSA CPAP treatment results in a significant early improvement in cognitive function but not in emotional status.


Influence of Heterologous and Homologous Vaccines, and Their Components, on the Host Immune Response and Protection Against Experimental Caprine Paratuberculosis.
Vaccination against paratuberculosis, a chronic disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map), has been considered as the most effective control method. However, protection is incomplete, and the mechanisms operating in the response of the animals to vaccination are not fully understood. Therefore, this study analyzed the immune response and the effects on protection against Map infection, elicited by paratuberculosis (Silirum®) and tuberculosis (heat-inactivated M. bovis [HIMB]) vaccines and their components in a caprine experimental model. Fifty goat kids were divided into 10 groups (n = 5) according to their vaccination (Silirum®, HIMB and nonvaccinated), immunization (inactivated bacteria or adjuvant), and/or infection. Oral challenge with Map was performed 45 days postvaccination/immunization (dpv), and animals were euthanized at 190 dpv. Peripheral immune response and proportion of lymphocyte subpopulations were assessed monthly by enzyme-linked immunosorbent assay and flow cytometry analysis, respectively. Local immune response, proportion of tissue lymphocyte subpopulations, Map detection (polymerase chain reaction), and histological examination were conducted in gut-associated lymphoid tissues. All infected groups developed paratuberculosis granulomatous lesions despite vaccination or immunization. The Silirum® and HIMB-vaccinated groups showed a considerable lesion reduction consistent with a significant peripheral cellular and humoral immune response. Besides, a lower number of granulomas were observed in groups immunized with inactivated bacteria and adjuvants in comparison to nonvaccinated and infected group. However, despite not being significant, this reduction was even higher in adjuvant immunized groups, which developed milder granulomatous lesion with no detectable peripheral immune responses associated with immunization. No changes in the peripheral and local proportion of lymphocyte subsets or local immune response were detected in relation to either vaccination/immunization or infection. Despite that paratuberculosis and tuberculosis vaccination showed a partial and cross-protection against Map infection, respectively, only histological examination could assess the progression of infection in these animals. In addition, the pattern observed in the reduction of the lesions in adjuvant immunized groups suggests the possible involvement of a nonspecific immune response that reduces the development of granulomatous lesions.


Microcystic adnexal carcinoma. Case report and review of the literature.
Microcystic adnexal carcinoma is an aggressive, locally destructive cutaneous neoplasm with a high rate of recurrence. This tumor is often misdiagnosed clinically and histologically. It usually occurs in middle-aged to older adults. We describe a 44-year-old man with a large microcystic adnexal carcinoma that was present for more than 20 years. The tumor invaded the perichondrium, muscle, nerve, and blood vessel adventitia. A review of the literature suggests that these tumors are often histologically misdiagnosed because the biopsy specimens may be too small to reveal all the characteristic histologic features. The clinical presence of marked induration, a smooth surface, and, possibly, sensory changes should alert the clinician to the possibility of this neoplasm. The initial biopsy specimen must be large enough to demonstrate the identifying histologic features. Mohs surgery is currently the treatment of choice for microcystic adnexal carcinoma, as it often spreads far beyond clinically evident tumor.


Transforming a Sword into a Knife: Persistent Phototoxicity Inhibition and Alternative Therapeutical Activation of Highly-Photosensitive Phytochlorin.
The phototoxicity of photosensitizers (PSs) is a double-edged sword with one edge beneficial for destroying tumors while the other is detrimental to normal tissues, and the conventional "OFF-ON" strategy provides temporary inhibition so that phototoxicity would come sooner or later due to the inevitable retention and transformation of PSs in vivo. We herein put forward a strategy to convert "double-edged sword" PSs into "single-edged knife" ones with simultaneously persistent phototoxicity inhibition and alternative multiple therapeutical activation. The Chlorin e6 (Ce6) as the PS model directly assembles with Cu2+ ions into nanoscale frameworks (nFs) whose Cu2+-coordination includes both carboxyl groups and a porphyrin ring of Ce6 instead of Fe3+/Mn2+-coordination with only carboxyl groups. Compared to the high phototoxicity of Ce6, the nFs exhibit efficient energy transfer due to the dual-coordination of paramagnetic Cu2+ ions and the aggregation, achieving the persistent and high phototoxicity inhibition rate of >92%. Alternatively, the nFs not only activate a high photoacoustic contrast and near-infrared (NIR)-driven photothermal efficacy (3.5-fold that of free Ce6) due to the aggregation-enhanced nonradiative transition but also initiate tumor microenvironment modulation, structure disassembly, and chemodynamic effect by Cu2+ ions. Given these merits, the nFs achieve long-term biosecurity, no retina injury under sunlight, and a higher therapeutical output than the photodynamic effect of Ce6. This work presents a possibility of converting numerous highly phototoxic porphyrins into safe and efficient ones.


Electro-Driven in Situ Construction of Functional Layer Using Amphoteric Molecule: The Role of Tryptophan in Ion Sieving.
The permselective separation of monovalent ions from the solution with the coexistence of multivalent ions was required in the industry of the wastewater treatment and resource recycling. Here, in this work, a novel electro-driven in situ modification method was utilized in the positively charged tryptophan solution to prepare highly permselective cation exchange membrane (CEM). We have optimized the process conditions and discussed the modification mechanism by drawing upon the fouling phenomenon in the membrane separation processes. A series of conventional characterization methods such as scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and electrochemical impedance spectroscopy (EIS) were used to investigate the structure and performance changes after the modification. The SEM-energy-dispersive X-ray (SEM-EDX) was introduced for analyzing the transfer of Na+ and Mg2+ in the functional modification layer and the membrane matrix, thus illustrating the sieving mechanism for the modified membranes. The resultant membranes were observed to have the changed interstructure and the multivalent-ion-repulsive modification layer. Due to the channel filling and electrostatic repulsion effect, the electro-driven tryptophan endowed the pristine CMX with superior monovalent cation permselectivity (PMg2+Na+: 6-35), which was higher than that of pristine CMX and the commercial Neosepta CIMS. It confirms that the proposed electro-driven tryptophan in situ modification method could effectively help improve the membrane permselectivity by structurally forming stable crystallization on and within the membrane, which provides a feasible choice for the cation exchange membrane modification.


The role of kidney injury molecule-1 in predicting cardiorenal syndrome type 1 after diuretic treatment.
Cardiorenal syndrome (CRS) is defined as acute or chronic dysfunction in the heart and kidney due to important interactions between the heart and kidney disease. The aim of this study was to evaluate prediction of CRS type 1 by measuring kidney injury molecule-1 (KIM-1) and to establish early diagnosis of acute kidney injury (AKI). During 2015-2016, 146 patients who were admitted to the emergency service with acute decompensated HF were included in the study. We investigated urinary KIM-1 levels in 146 consecutive patients with decompensated heart failure before and after diuretic treatment. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS - version 21.0)/Windows Statistical Software. P-values less than < 0.05 were considered significant. There was a moderate negative correlation between the percentage change of creatinine values and the percentage change of KIM-1 values (r = -0.357, p = 0.016). There was no statistically significant relationship between KIM-1 and the development of CRS type 1 (p = 0.011). No statistically significant relationship was observed between KIM-1 levels and the development of CRS type 1. In addition, there was no correlation between mortality in patients and KIM-1 values. It is thought that KIM-1 is not a potential prognostic indicator because renal tubular damage is only one of many factors in the pathophysiology of CRS type 1 and heart failure.


The current status of myeloid growth factor therapy.
Supralethal chemotherapy has been used in an attempt to cure certain malignancies by employing doses of cytotoxic agents beyond conventional limits. The resulting damage to the bone marrow requires rescue with an infusion of autologous or allogenic marrow to repopulate the haemopoietic system. The recent availability of marrow stimulants for clinical use may prove to be a major advance in oncology as early evidence suggests that they can reduce cytotoxic drug induced myelosuppression and possibly allow escalation of chemotherapy with improved tumour responsiveness. Such growth factors may also improve primary marrow disorders. This article outlines the properties of the myeloid growth factors and then reviews the important clinical conditions in which they have been employed so far. Erythropoietin and lymphoid growth factors are not dealt with.


Astaxanthin protects oxidative stress mediated DNA damage and enhances longevity in Saccharomyces cerevisiae.
Reactive oxygen species (ROS) have long been found to play an important role in oxidative mediated DNA damage. Fortunately, cells possess an antioxidant system that can neutralize ROS. However, oxidative stress occurs when antioxidants are overwhelmed by ROS or impaired antioxidant pathways. This study was carried out to find the protective effect of astaxanthin on the yeast DNA repair-deficient mutant cells under hydrogen peroxide stress. The results showed that astaxanthin enhances the percent cell growth of rad1∆, rad51∆, apn1∆, apn2∆ and ogg1∆ cells. Further, the spot test and colony-forming unit count results confirmed that astaxanthin protects DNA repair mutant cells from oxidative stress. The DNA binding property of astaxanthin studied by in silico and in vitro methods indicated that astaxanthin binds to the DNA in the major and minor groove, and that might protect DNA against oxidative stress induced by Fenton's reagent. The intracellular ROS, 8-OHdG level and the DNA fragmentation as measured by comet tail was reduced by astaxanthin under oxidative stress. Similarly, reduced nuclear fragmentation and chromatin condensation results suggest that astaxanthin might reduce apoptosis. Finally, we show that astaxanthin decreases the accumulation of mutation rate and enhances the longevity of DNA repair-deficient mutants' cells during a chronological lifespan.


Arabidopsis thaliana contains two differentially expressed farnesyl-diphosphate synthase genes.
The enzyme farnesyl-diphosphate synthase (FPS; EC 126.96.36.199/EC 126.96.36.199) catalyzes the synthesis of farnesyl diphosphate (FPP) from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). This reaction is considered to be a rate-limiting step in isoprenoid biosynthesis. Southern blot analysis indicates that Arabidopsis thaliana contains at least 2 genes (FPS1 and FPS2) encoding FPS. The FPS1 and FPS2 genes have been cloned and characterized. The two genes have a very similar organization with regard to intron positions and exon sizes and share a high level of sequence similarity, not only in the coding region but also in the intronic sequences. Northern blot analysis showed that FPS1 and FPS2 have a different pattern of expression. FPS1 mRNA accumulates preferentially in roots and inflorescences, whereas FPS2 mRNA is predominantly expressed in inflorescences. The cDNA corresponding to the FPS1 gene was isolated by functional complementation of a mutant yeast strain defective in FPS activity (Delourme, D., Lacroute, F., and Karst, F. (1994) Plant Mol. Biol. 26, 1867-1873). By using a reverse transcription-polymerase chain reaction strategy we have cloned the cDNA corresponding to the FPS2 gene. Analysis of the FPS2 cDNA sequence revealed an open reading frame encoding a protein of 342 amino acid residues with a predicted molecular mass of 39,825 Da. FPS1 and FPS2 isoforms share an overall amino acid identity of 90.6%. Arabidopsis FPS2 was able to rescue the lethal phenotype of an ERG20-disrupted yeast strain. We demonstrate that FPS2 catalyzes the two successive condensations of IPP with both DMAPP and geranyl diphosphate leading to FPP. The significance of the occurrence of different FPS isoforms in plants is discussed in the context of the complex organization of the plant isoprenoid pathway.


Seroepidemiology of the recent mumps virus outbreaks in Ireland.
Two recent mumps outbreaks have occurred in Ireland in 2004/2005 and 2008/2009. To retrospectively investigate any potential shifts in the gender bias and age profile and to identify cohorts who are maintaining mumps virus in circulation. 2600 cases of acute mumps infection, as determined by the presence of mumps-specific IgM in sera and oral fluids, were confirmed at the National Virus Reference Laboratory. Acute mumps infection occurred more frequently in males with a ratio of approximately 2:1 in the 1-9 and 10-19 years old age groups. A 3:2 ratio was observed in the 20-29 years old cohort and the 30+ age group did not show a gender bias. Serological evidence of prior immunological exposure to mumps virus, as determined by the presence of mumps-specific IgG, was high and similar in males and females of all age cohorts (93.1-100%). A significant increase in the number of acute mumps cases in the ≥30 years old age group was observed. This increase was most striking in the periods between the outbreaks (71.1% in 2007 and 56.2% in 2010). Acute mumps infection showed a male gender bias. The consistent and significant increase of mumps infection in the ≥30 years old age group which is also evident in the periods between outbreaks suggests that this may be the cohort maintaining the mumps virus in circulation.


Expression of ETV6-NTRK in classical, cellular and mixed subtypes of congenital mesoblastic nephroma.
Congenital mesoblastic nephroma (CMN) is the commonest renal tumour of infancy, with classical, cellular and mixed histological subtypes described. A specific ETV6-NTRK3 fusion-gene product is reported in association with the cellular variant. The aim was to investigate the relationship between the presence of this product and morphological phenotype using paraffin-embedded archival material. Cases of CMN from a single centre during a 15-year period (1989-1994) were identified, anonymized and blindly classified using morphological criteria. RNA was extracted from frozen and paraffin sections for both conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. Fifteen samples were analysed; two were non-informative and three expressed ETV6-NTRK3 using both techniques, two showing similar expression, whilst one showed expression two orders of magnitude lower, from a cellular tumour. All fusion positive cases were previously classified as cellular subtype. Six patients had mixed-subtype tumours in which the cellular components, morphologically indistinguishable from cellular tumours, were fusion negative, as were all classical cases. Real-time PCR Taqman assays, using both fixed and frozen tissue, provide highly reproducible detection and quantification of fusion transcript expression. Differences in expression levels may explain previous conflicting data on fusion gene detection in these tumours.


Patient-derived organoids for personalized gallbladder cancer modelling and drug screening.
Gallbladder carcinoma (GBC) is a relatively rare but highly aggressive cancer with late clinical detection and a poor prognosis. However, the lack of models with features consistent with human gallbladder tumours has hindered progress in pathogenic mechanisms and therapies. We established organoid lines derived from human GBC as well as normal gallbladder and benign gallbladder adenoma (GBA) tissues. The histopathology signatures of organoid cultures were identified by H&E staining, immunohistochemistry and immunofluorescence. The genetic and transcriptional features of organoids were analysed by whole-exome sequencing and RNA sequencing. A set of compounds targeting the most active signalling pathways in GBCs were screened for their ability to suppress GBC organoids. The antitumour effects of candidate compounds, CUDC-101 and CUDC-907, were evaluated in vitro and in vivo. The established organoids were cultured stably for more than 6 months and closely recapitulated the histopathology, genetic and transcriptional features, and intratumour heterogeneity of the primary tissues at the single-cell level. Notably, expression profiling analysis of the organoids revealed a set of genes that varied across the three subtypes and thus may participate in the malignant progression of gallbladder diseases. More importantly, we found that the dual PI3K/HDAC inhibitor CUDC-907 significantly restrained the growth of various GBC organoids with minimal toxicity to normal gallbladder organoids. Patient-derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs.


Effective fast-track ambulatory care pathway for patients with COVID-19 at risk for poor outcome: the COVID-A2R model in a hospital emergency department.
To evaluate the effectiveness of a care pathway (Spanish acronym, COVID-A2R) through which patients with SARS-CoV-2 infection were referred by a hospital emergency department (ED) for fast-track in-person outpatient clinic care if they did not have respiratory insufficiency but were at high risk for complications and poor outcome. Retrospective cohort of patients referred to the COVID-A2R pathway after being diagnosed with COVID-19 by reverse transcription polymerase chain reaction assay in a tertiary care hospital ED between January 7 and February 17, 2021. The inclusion criteria were 1) absence of pneumonia but presence of serious comorbidity and/or elevated biomarkers of inflammation, and 2) pneumonia with or without elevated inflammatory markers but without respiratory insufficiency. The main outcome was need for an emergency department revisit with hospital admission and time from ED evaluation to hospitalization. Secondary outcomes were the number of COVID-A2R visits and the potential economic impact. We included 278 patients with a median age of 57 years (57.9% men) and a median Charlson Comorbidity Index of 1. The median time since onset of symptoms was 7 days (interquartile range, 4-11 days). Pneumonia was diagnosed in 71.8%, and 64.7% required only 1 in-person visit in the COVID-A2R pathway. No revisits to the ED were needed by 87.8% (83.4%-91.1%) of the patients. Of the 34 patients who were hospitalized, 88.2% were admitted within 5 days. The COVID-A2R model potentially saved 1708 days of hospitalization. The fast-track ambulatory care model was effective after emergency department discharge of patients with COVID-19 without respiratory insufficiency but with clinical or laboratory indicators of risk for poor outcome.


Modeling conception as an aggregated Bernoulli outcome with latent variables via the EM algorithm.
We describe a general method for analyzing aggregated Bernoulli outcomes. The research is motivated by an epidemiological reproductive study where the outcome was whether pregnancy was detected in a woman's particular menstrual cycle and the Bernoulli "trials" corresponded to days with intercourse during the cycle. Each cycle is either "viable" or not, i.e., is or is not susceptible to conception. We develop an EM algorithm approach to maximizing the observed-data pseudo-likelihood, based on a set of unobservable latent outcomes linked to the specific days with intercourse. This method is flexible in that it allows one to model effect of covariates on the susceptibility factor and on the latent outcomes. Application of the method to fertility studies enables one to investigate covariates with a long-term or transient effect on the daily conception probability. A complication is that most couples contribute more than one cycle in a prospective study. A generalized estimating equation approach adjusts for the dependency among outcomes within individual couples. The method can be applied in any setting where dependency among Bernoulli trials is induced by a susceptibility factor and the trial outcomes are only observable in the aggregate.


Confinement Assembly in Polymeric Micelles Enables Nanoparticle Superstructures with Tunable Molecular-Like Geometries.
The self-assembly of a small number of nanoparticles into superstructures that mimic the geometry of molecules provides an unprecedented route for creating materials with precisely defined structures and potentially programmable functionalities. Such nanoparticle clusters (NPCs), also known as colloidal molecules, have a wide range of applications due to the decisive ensemble effect. Here, a universal and straightforward strategy is developed to construct NPCs with tunable molecular-like geometries by confining the self-assembly of hydrophobic nanoparticles within micelles formed by amphiphilic copolymers. It is found that confinement assembly of both spherical and anisotropic nanoparticles can lead to NPCs, the molecular-like conformation of which is widely tunable by adjusting the ratio between copolymers and nanoparticles. Mechanistic studies reveal the formation of large-vesicle intermediates along the path toward forming NPCs. This work establishes a facile and general strategy of assembling finite nanoparticles with precisely tunable geometries without introducing any directional interactions, which can accelerate the exploration of clustered superstructures toward broad applications.


Radiation of Dynamic Toroidal Moments.
Dynamic toroidal dipoles, a distinguished class of fundamental electromagnetic sources, receive increasing interest and participate in fascinating electrodynamic phenomena and sensing applications. As described in the literature, the radiative nature of dynamic toroidal dipoles is sometimes confounded, intermixing with static toroidal dipoles and plasmonic dark modes. Here, we elucidate this issue and provide proof-of-principle experiments exclusively on the radiation behavior of dynamic toroidal moments. Optical toroidal modes in plasmonic heptamer nanocavities are analyzed by electron energy loss spectroscopy and energy-filtered transmission electron microscopy supported by finite-difference time-domain numerical calculations. Additionally, their corresponding radiation behaviors are experimentally investigated by means of cathodoluminescence. The observed contrasting behaviors of a single dynamic toroidal dipole mode and an antiparallel toroidal dipole pair mode are discussed and elucidated. Our findings further clarify the electromagnetic properties of dynamic toroidal dipoles and serve as important guidance for the use of toroidal dipole moments in future applications.


The exopolyphosphatase gene from sulfolobus solfataricus: characterization of the first gene found to be involved in polyphosphate metabolism in archaea.
Inorganic polyphosphate (polyP) polymers are widely distributed in all kinds of organisms. Although the presence of polyP in members of the domain Archaea has been described, at present nothing is known about the enzymology of polyP metabolism or the genes involved in this domain. We have cloned, sequenced, and overexpressed an exopolyphosphatase (PPX) gene (ppx) from thermophilic Sulfolobus solfataricus. The gene codes for a functional PPX and possesses an open reading frame for 417 amino acids (calculated mass, 47.9 kDa). The purified recombinant PPX was highly active, degrading long-chain polyP (700 to 800 residues) in vitro at 50 to 60 degrees C. The putative PPXs present in known archaeal genomes showed the highest similarity to yeast PPXs. In contrast, informatic analysis revealed that the deduced amino acid sequence of S. solfataricus PPX showed the highest similarity (25 to 45%) to sequences of members of the bacterial PPXs, possessing all of their conserved motifs. To our knowledge, this is the first report of an enzyme characterized to be involved in polyP metabolism in members of the Archaea.


Hemodialysis Is Associated With Increased Peripheral Artery Occlusive Disease Risk Among Patients With End-Stage Renal Disease: A Nationwide Population-Based Cohort Study.
To investigate the effect of different dialysis modalities on the incidence of peripheral artery occlusive disease (PAOD) among patients with end-stage renal disease (ESRD) in a large population-based cohort study. The cohort study included 26,927 ESRD patients who underwent hemodialysis (17,737 patients, hemodialysis [HD] cohort) or peritoneal dialysis (PD, 9190 patients, PD cohort), and 107,588 matched controls between 2000 and 2010. A Cox proportional hazards model was to evaluate the risk of PAOD in the ESRD underwent HD or PD. Based on a mean follow-up period of 2.92, 3.64, and 4.91 years in the PD, HD, and control cohorts, respectively, the incidences of PAOD were 18.1% and 8.10% higher in the HD and PD cohorts, respectively, compared with the control cohort (log-rank test P < 0.001). The patients who underwent HD or PD exhibited a higher risk of PAOD compared with the control cohort regardless of age, sex, and presence or absence of comorbidities. In addition, the incidence of PAOD in the PD cohort and the propensity score-matched HD cohort were 12.4 and 20.7 per 1000 person-years, respectively, with a hazard ratio of 1.92 (95% confidence interval = 1.62-2.28) in HD patients, compared with the PD cohort. This nationwide population-based cohort study suggested a significantly increased risk of PAOD among ESRD patients. Moreover, the PD patients have a lower risk of developing PAOD compared with the HD cohort, indicating the beneficial roles of PD in reducing PAOD risk in ESRD patients.


[Diagnosis of diabetes mellitus in children].
Diabetes in childhood is essentially represented by the type 1 or insulin-dependent diabetes mellitus (IDDM). Classical symptoms (polyuria, polydipsia, asthenia, weight loss) are usually present at the first consultation and allow an immediate diagnosis at the physician's office by performing capillary (finger-prick) blood glucose measurement (> or = 200 mg/dL) and urine-stripe test (detection of glucosuria and ketonuria). A diagnosis performed at this stage of the disease leads to the admission of the child at hospital, in order to institute the insulintherapy without delay. This attitude should permit to avoid the rapid development of diabetic keto-acidosis, which is at present too much frequent at diagnosis (50% of the cases) and which is associated with potential risks of severe complications in children. In case of incidental detection of hyperglycemia without ketonuria in childhood, the differential diagnoses of early IDDM are the rare form of familial non insulin-dependent diabetes with onset in childhood (MODY: maturity-onset diabetes of the young) and the transient hyperglycemia in childhood. Finally, diabetes could also develop in the course of an other chronic disease (i.e. cystic fibrosis) or as part of genetical syndroms.


[Neurocysticercosis in the South-East of France 1988-1998].
Neurocysticercosis is commonly observed in developing countries but can also occur in industrialized countries. The aim of this work was to analyze diagnostic and therapeutic data on cases of neurocysticercosis diagnosed in southeastern France over the last 10 years. We collected data from patient files and compared them with those reported in the literature. We collected 29 cases of neurocysticercosis diagnosed in southeastern France between 1988 and 1999. None of the patients had acquired the disease in France. Seizures were the most common inaugural sign. Four patients had skin lesions and very few had radiologically identifiable muscle calcifications. CT scan and MRI provided the diagnosis of neurocysticercosis and contributed to follow-up. Brain imaging showed cyst formation and calcifications. Cysticercosis serology was positive in only 52% of our patients. Antiparasite treatments with albendazole provided improvement in most patients although aggravation was observed in 4 despite a well-conducted regimen. There was one death. Neurological manifestations, particularly seizures, in a patient returning from an endemic zone should prompt search for neurocysticercosis with brain CT and MRI. Regression of clinical and radiological signs with treatment confirms the diagnosis.


An amide based dipodal Zn(2+) complex: nano-molar detection of HSO(4) (−) in a semi-aqueous system.
A new chromogenic dipodal Zn2+ complex (4) bearing an amide group has been synthesized. The anion binding profile of this sensor was investigated with fluorescence and UV-Vis spectroscopy. The receptor 4 has high affinity for HSO4 − with a binding constant of 3.5 × 104 M−1 and a detection limit of 50 nM. The binding ability was confirmed with spectroscopic methods and density functional theory calculation (DFT).


Detection of Physiological Signals Based on Graphene Using a Simple and Low-Cost Method.
Despite that graphene has been extensively used in flexible wearable sensors, it remains an unmet need to fabricate a graphene-based sensor by a simple and low-cost method. Here, graphene nanoplatelets (GNPs) are prepared by thermal expansion method, and a sensor is fabricated by sealing of a graphene sheet with polyurethane (PU) medical film. Compared with other graphene-based sensors, it greatly simplifies the fabrication process and enables the effective measurement of signals. The resistance of graphene sheet changes linearly with the deformation of the graphene sensor, which lays a solid foundation for the detection of physiological signals. A signal processing circuit is developed to output the physiological signals in the form of electrical signals. The sensor was used to measure finger bending motion signals, respiration signals and pulse wave signals. All the results demonstrate that the graphene sensor fabricated by the simple and low-cost method is a promising platform for physiological signal measurement.


[Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) leading to the diagnosis of Wilson's disease].
Authors describe the case of a patient suffering from Thrombotic Thrombocytopenic Purpura--Hemolytic-Uremic syndromee. Any cause of the disease was not found, except signs of liver injury. The etiology of indefinite liver disease that had been diagnosed several years before was examined. Wilson's disease was considered as a final eventuality. The finding of 488 micrograms of copper in the dry liver tissue confirmed the diagnosis of Wilson's disease in the end.


[Chronic arterial insufficiency of the bellow knee arteries (retrospective study)].
The study involves 70 patients for the period from 1990 till 2001. Male are 60 of them and female are 10 patients. A total of 77 surgical procedures were performed on these patients with highest number per year are 1990 and 2001. Results are as follows: patent reconstruction--47, graft thrombosis not requiring immediate amputation--18, graft thrombosis requiring immediate amputation--11, and death in one case. Fifty five patients had grafts to the bellow the knee popliteal artery, and 23 of them received grafts to a tibial or peroneal artery. The stage distribution of patients is as follows: stage II--5 patients, stage III--50 patients, and stage IV--22 patients. Rethrombosis rate increased with the higher stages of the disease. In six cases ipsilateral deep venous thrombosis was diagnosed by duplex ultrasound study. Synthetic grafts were used in 24 of patients, nine of them received composed grafts, and in 38 cases venous conduits were employed. Diabetes mellitus was a comorbid condition in 13 patients. Thirty one (40.26%) of the grafts thrombosed.


Effect of a PEGylated lipid on the dispersion stability and dynamic surface tension of aqueous DPPC and on the interactions with albumin.
Dispersions of dipalmitoylphosphatidylcholine (DPPC) vesicles at 0.1 wt % (1000 ppm) in aqueous isotonic buffer solutions produced by extensive sonication were found to be colloidally stable for hours and days. They also had very low (<10 mN/m) dynamic surface tension minima (DSTM) under pulsating area conditions at 37 degrees C at 20 rpm area pulsation rate. When a 1000 ppm DPPC dispersion was mixed with a stable solution of 1000 ppm bovine serum albumin (BSA), it became colloidally unstable, aggregating within minutes, implying that heterocoagulation between lipid vesicles and albumin takes place. The heterocoagulated dispersion produced high DSTM because the lipid transport rate to the interface became slower. Moreover, the protein may have been transported to the surface faster and adsorbed more than the lipid at the surface. DPPC lipid vesicles were modified for reducing aggregation with other vesicles or with the protein with the addition of a small weight fraction of a neutral "PEGylated" lipid, with a covalently bonded poly(ethylene glycol) (PEG) group. The mixed vesicles were found to be quite more stable than the DPPC vesicles, remaining stable for months, apparently stabilized by steric forces. The colloidal stability at the initial stages of coagulation was evaluated quantitatively from the Fuchs-Smoluchowski stability ratio W. When the modified lipid vesicle dispersion was mixed with the albumin, the vesicles showed no tendency to aggregate with the albumin molecules for days, also probably because of steric repulsion between the PEGylated lipid and the protein. Finally, the mixed lipid dispersions maintained their low DSTM as did the DPPC vesicles without the albumin, and also in the presence of albumin. The results have implications on the use of DPPC or DPPC-based lipids in treating alveolar respiratory diseases without albumin inhibition of their surface tension lowering ability.


Irish on the move.
Trends in emigration from Ireland over time are reviewed. "During the eighteenth and nineteenth centuries overseas migration to the United States and seasonal harvest migration to Britain were the main types of movement, but over the past 100 years the Irish have developed a special affinity for settling in British towns. Although the outflow was halted for a time during the 1970s, when return migration took over, the 1980s have seen a renewal of the exodus. This time, however, the character of the flow has changed from predominantly low-skill construction and factory workers to embrace better-educated emigrants, including many graduates. This shift reflects Ireland's changing position in the international market for labour."


Assessing the fate and effects of nano aluminum oxide in the terrestrial earthworm, Eisenia fetida.
Nano-sized aluminum is currently being used by the military and commercial industries in many applications including coatings, thermites, and propellants. Due to the potential for wide dispersal in soil systems, we chose to investigate the fate and effects of nano-sized aluminum oxide (Al2O3), the oxidized form of nano aluminum, in a terrestrial organism. The toxicity and bioaccumulation potential of micron-sized (50-200 microm, nominal) and nano-sized (11 nm, nominal) Al2O3 was comparatively assessed through acute and subchronic bioassays using the terrestrial earthworm, Eisenia fetida. Subchronic (28-d) studies were performed exposing E. fetida to nano- and micron-sized Al2O3-spiked soils to assess the effects of long-term exposure. No mortality occurred in subchronic exposures, although reproduction decreased at >or=3,000 mg/kg nano-sized Al2O3 treatments, with higher aluminum body burdens observed at 100 and 300 mg/kg; no reproductive effects were observed in the micron-sized Al2O3 treatments. In addition to toxicity and bioaccumulation bioassays, an acute (48-h) behavioral bioassay was conducted utilizing a soil avoidance wheel in which E. fetida were given a choice of habitat between control, nano-, or micron-sized Al2O3 amended soils. In the soil avoidance bioassays, E. fetida exhibited avoidance behavior toward the highest concentrations of micron- and nano-sized Al2O3 (>5,000 mg/kg) relative to control soils. Results of the present study indicate that nano-sized Al2O3 may impact reproduction and behavior of E. fetida, although at high levels unlikely to be found in the environment.


[Multiple sclerosis and pregnancy (two additional cases)].
The authors made a short analysis of the epidemiology, etiology, pathogenesis, clinical presentation and treatment of multiple sclerosis. There were presented facts about the influence of pregnancy over the progress of this neurological disease, and the effect of multiple sclerosis on the pregnancy and delivery development. There also were described two clinical cases of pregnant women with multiple sclerosis, who delivered in the last 10 years in Clinic of Obstetrics in MBAL-Pleven.


Fluorometric chemosensors. Interaction of toxic heavy metal ions Pb(II), Cd(II), and Hg(II) with novel mixed-donor phenanthroline-containing macrocycles: spectrofluorometric, conductometric, and crystallographic studies.
The macrocycles L(1)-L(3) incorporating N(2)S(3)-, N(2)S(2)O-, and N(2)S(2)-donor sets, respectively, and containing the 1,10-phenanthroline unit interact in acetonitrile solution with heavy metal ions such as Pb(II), Cd(II), and Hg(II) to give 1:1 ML, 1:2 ML(2), and 2:1 M(2)L complex species, which specifically modulate the photochemical properties of the ligands. The stoichiometry of the complex species formed during spectrofluorometric titrations and their formation constants in MeCN at 25 degrees C were determined from fluorescence vs M(II)/L molar ratio data. The complexes [Pb(L(1))][ClO(4)](2).(1)/(2)H(2)O (1), [Pb(L(2))][ClO(4)](2).MeNO(2) (1a), [Pb(L(3))(2)][ClO(4)](2).2MeCN (1b), and [Cd(L(3))][NO(3)](2) (2b) were also characterized by X-ray diffraction studies. The conformation adopted by L(1)-L(3) in these species reveals the aliphatic portion of the rings folded over the plane containing the heteroaromatic moiety with the ligands trying to encapsulate the metal center within their cavity. In 1, 1a, and 2b the metal ion completes the coordination sphere by interacting with counteranion units and solvent molecules. On the contrary, the 1:2 complex 1b shows Pb(II) sandwiched between two symmetry-related molecules of L(3) reaching an overall [4N + 4S] eight-coordination.


Digitonthophagus gazella auctorum: an unfortunate case of mistaken identity for a widely introduced species (Coleoptera: Scarabaeidae: Scarabaeinae: Onthophagini).
At risk of committing entomological heresy, we question the identity of a dung-burying beetle species that originates from Africa and has been introduced first into Hawaii and subsequently to Australasia, North America, and South America (Fincher 1986; Edwards 2007; Noriega et al. 2010) for pasture improvement and biological control of dung-breeding flies (Waterhouse 1974; Bornemissza 1979). Under the name Onthophagus gazella (Fabricius 1787), it was the first species selected for introduction into Australia by the CSIRO Dung Beetle Project (Bornemissza 1976; Edwards 2007). Firstly, in 1968, a "tropical strain" was introduced from Hawaii where it had become established after introduction from Zimbabwe in 1957 (Markin & Yoshioka 1998). Later, after establishment of the CSIRO Dung Beetle Research Unit in Pretoria in 1970, a "cold" or "even rainfall strain" was introduced into Australia directly from South Africa (Bornemissza 1976) (even rainfall region = south coast of Eastern Cape). The species was subsequently introduced into the southern continental United States of America (Victoria County, Texas) from Hawaii (Montes de Oca & Halffter 1998) then elsewhere into southeastern and southwestern states from Hawaii and breeding colonies from Australia (Anderson & Loomis 1978). It has since expanded its range through Mexico, Central America, and the Caribbean to coastal Colombia (Kohlmann 1994; Noriega 2002; Noriega et al. 2006, 2011). Expansion of its range within central southern South America (Noriega et al. 2010) has been assisted by introductions into Brazil from the United States of America since the 1980s (Bianchin et al. 1998), and others into Venezuela and Chile (Vidaurre et al. 2008). More recently, it has been introduced into quarantine and field trials in New Zealand (Forgie et al. 2013) using individuals originating from the south coast of the Eastern Cape and Northwest Province of South Africa (S. Forgie, personal communication).


Expression of aquaporin 1, 5 and 9 in the ovarian follicles of cycling and early pregnant pigs.
Aquaporins (AQPs) are water channel proteins responsible for water homeostasis and important for proper functioning of all body systems, including reproductive structures. This study was designed to determine their localization and quantitative changes in the pig ovary during different stages of the estrous cycle and early pregnancy. The expression of AQP 1, 5 and 9 proteins was determined by immunocytochemistry and Western blot analyses. AQP1 was found in the plasma membranes of capillary endothelium, AQP5 - in the plasma membranes of granulosa cells of developing follicles and flattened follicle cells of the primordial follicles, and AQP9 - in granulosa cells of the developing follicles. In the cyclic pigs, the expression of AQP1 and 5 proteins was the highest on Days 18-20, but did not change significantly between Days 2-4, 10-12 and 14-16 of the cycle. In pregnant pigs (Days 14-16 and 30-32), the expression of AQP1 and 5 did not change and was similar to that observed during Days 10-12 and 14-16. In turn, AQP9 expression did not change between all studied periods. In conclusion, studied AQP are localized in different cells populations, the endothelial and granulosa cells, and AQP1 and 5 seem to be crucial for follicular development in pigs.


Hepatic insulin resistance both in prediabetic and diabetic patients determines postprandial lipoprotein metabolism: from the CORDIOPREV study.
Previous evidences have shown the presence of a prolonged and exaggerated postprandial response in type 2 diabetes mellitus (T2DM) and its relation with an increase of cardiovascular risk. However, the response in prediabetes population has not been established. The objective was to analyze the degree of postprandial lipemia response in the CORDIOPREV clinical trial (NCT00924937) according to the diabetic status. 1002 patients were submitted to an oral fat load test meal (OFTT) with 0.7 g fat/kg body weight [12 % saturated fatty acids (SFA), 10 % polyunsaturated fatty acids (PUFA), 43 % monounsaturated fatty acids (MUFA), 10 % protein and 25 % carbohydrates]. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 h during postprandial state. Postprandial triglycerides (TG) concentration at any point >2.5 mmol/L (220 mg/dL) has been established as undesirable response. We explored the dynamic response in 57 non-diabetic, 364 prediabetic and 581 type 2 diabetic patients. Additionally, the postprandial response was evaluated according to basal insulin resistance subgroups in patients non-diabetic and diabetic without pharmacological treatment (N = 642). Prevalence of undesirable postprandial TG was 35 % in non-diabetic, 48 % in prediabetic and 59 % in diabetic subgroup, respectively (p < 0.001). Interestingly, prediabetic patients displayed higher plasma TG and large triacylglycerol-rich lipoproteins (TRLs-TG) postprandial response compared with those non-diabetic patients (p < 0.001 and p = 0.003 respectively). Moreover, the area under the curve (AUC) of TG and AUC of TRLs-TG was greater in the prediabetic group compared with non-diabetic patients (p < 0.001 and p < 0.005 respectively). Patients with liver insulin resistance (liver-IR) showed higher postprandial response of TG compared with those patients with muscle-IR or without any insulin-resistance respectively (p < 0.001). Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external aggression, such as OFTT compared with nondiabetic patients. The postprandial response increases progressively according to non-diabetic, prediabetic and type 2 diabetic state and it is higher in patients with liver insulin-resistance. To identify this subgroup of patients is important to treat more intensively in order to avoid future cardiometabolic complications.


[Duplication of animal model of ulcerative colitis and studies on rehabilitation effect of jianpiling prescription].
In this paper, the ulcerative colitis model of rats with immuno-method was reported and the mechanism of using Jianpiling for the treatment of ulcerative colitis was studied. The rats of experimental group were subdivided into 3 subgroups (A, B and C), 15% Jianpiling suspension was given to rats in subgroup A per os, 15% Bupi-Yichang Pill to rats in subgroup B per os, 4.5% SASP suspension to rats in subgroup C, and same amount of saline to rats in the control group. The therapeutic results showed that the anti-diarrhia, anti-infection and repairing function of tissue by Jianpiling were obviously better than those of Bupi-Yichang Pill and SASP. Serological exams also showed that Jianpiling was much better than other therapeutic groups in increasing nonspecific cellular immunity and lowering level of antibody against large intestine and IgG. These results suggested that the mechanism of Jianpiling on ulcerative colitis was realized by increasing cellular immunity, inhibiting humoral immunity and promoting immune modulation.


Stable cationic microparticles for enhanced model antigen delivery to dendritic cells.
The objectives of this work were (i) to prepare physically stable cationic microparticles and (ii) to study the impact of the surface properties on microparticle phagocytosis and the phenotype of dendritic cells (DC). Protein loaded biodegradable microparticles from poly(lactic-co-glycolic acid) [PLGA] were produced in a micromixer-based w/o/w solvent evaporation procedure. Anionic particles were obtained by using polyvinyl alcohol (PVA) as stabilizing agent; for cationic surfaces cetyltrimethylammonium bromide (CTAB) and chitosan/PVA or DEAE-dextran/PVA blends were evaluated. In phagocytosis studies human monocytes and monocyte-derived DC were incubated with microparticles and analysed by flow cytometry. While CTAB modified microparticles lost their positive charge and aggregated due to CTAB desorption from the particle surface, the modification with chitosan and DEAE-dextran resulted in stable microparticles without cell toxicity. Due to a very low endotoxin content, phagocytosis of anionic and cationic microparticles did not induce an upregulation of maturation-associated surface markers on DC. DEAE-dextran modified microparticles showed an enhanced model protein delivery into phagocytic cells. Overall, PLGA microparticles are suitable vehicles for protein delivery to DC, which might be used for DC-based cell therapies.


Quantum field theory of forward rates with stochastic volatility.
In a recent formulation of a quantum field theory of forward rates, the volatility of the forward rates was taken to be deterministic. The field theory of the forward rates is generalized to the case of stochastic volatility. Two cases are analyzed, first when volatility is taken to be a function of the forward rates, and second when volatility is taken to be an independent quantum field. Since volatility is a positive valued quantum field, the full theory turns out to be an interacting nonlinear quantum field theory in two dimensions. The state space and Hamiltonian for the interacting theory are obtained, and shown to have a nontrivial structure due to the manifold moving with a constant velocity. The no arbitrage condition is reformulated in terms of the Hamiltonian of the system, and then exactly solved for the nonlinear interacting case.


Topic-Based Instance and Feature Selection in Multilabel Classification.
Multilabel learning has been extensively studied in the past years, as it has many applications in different domains. It aims at annotating the labels for unseen data according to training data, which are often high dimensional in both instance and feature levels. The training data often have noisy and redundant information on these two levels. As an effective data preprocessing step, instance and feature selection should both be performed to find relevant training instances for each testing instance and relevant features for each label, respectively. However, most of the existing methods overlook the input-output correlation in each kind of selection. It will lead to the performance degradation. This article presents a formulation for multilabel learning from a topic view that exploits the dependence between features and labels in a topic space. We can perform effective instance and feature selection in the latent topic space, as the relationship between the input and output spaces is well captured in this space. The results from intensive experiments on various benchmarks demonstrate the effectiveness of the proposed framework.


Di- and triheteroarylalkanes via self-condensation and intramolecular Friedel-Crafts type reaction of heteroaryl alcohols.
An efficient synthetic approach to diheteroarylmethanes and 1,3-diheteroarylpropenes has been developed via Yb(III)-catalyzed sequential self-condensation of 2-furfuryl (or 2-thienyl or 3-indolyl) alcohols followed by intramolecular Friedel-Crafts type reaction and elimination of an aldehyde. This method offers a powerful entry and a potential alternative to the traditional synthesis of diheteroarylalkanes, which are precursors to the synthesis of several intriguing heteroaryls and more significantly, to the synthesis of biofuels.


Self-Efficacy Between Previous and Current Mathematics Performance of Undergraduate Students: An Instrumental Variable Approach to Exposing a Causal Relationship.
Self-efficacy has been argued theoretically and shown empirically to be an essential construct for students' improved learning outcomes. However, there is a dearth of studies on its causal effects on performance in mathematics among university students. Meanwhile, it will be erroneous to assume that results from other fields of studies generalize to mathematics learning due to the task-specificity of the construct. As such, attempts are made in the present study to provide evidence for a causal relationship between self-efficacy and performance with a focus on engineering students following a mathematics course at a Norwegian university. The adopted research design in the present study is a survey type in which collected data from first-year university students are analyzed using structural equation modeling with weighted least square mean and variance adjusted (WLSMV) estimator. Data were generated using mainly questionnaires, a test of prior mathematics knowledge, and the students' final examination scores in the course. The causal effect of self-efficacy was discerned from disturbance effects on performance by using an innovative instrumental variable approach to structural equation modeling. The findings confirmed a significant direct effect of the prior mathematics knowledge test (β = 0.52, SE = 0.01, p < 0.001) on self-efficacy, a significant direct effect (β = 0.43, SE = 0.19, p = 0.02) of self-efficacy on performance, and a substantial mediating effect (β = 0.22, SE = 0.10, p = 0.03) of self-efficacy between a prior mathematics knowledge test and performance. Prior mathematics knowledge and self-efficacy explained 30% variance of the performance. These findings are interpreted to be substantial evidence for the causal effect of self-efficacy on students' performance in an introductory mathematics course. The findings of the present study provide empirically supports for designing self-efficacy interventions as proxies to improve students' performance in university mathematics. Further, the findings of the present study confirm some postulates of Bandura's agentic social cognitive theory.


Functional analysis patterns of automatic reinforcement: A review and component analysis of treatment effects.
Functional analysis (FA) conditions include different antecedent or consequent events that may disrupt responding. Thus, varying patterns of FA differentiation may predict treatment outcomes of problem behavior maintained by automatic reinforcement. These patterns could be used to inform the development of individualized interventions. An approach to classifying these patterns is to categorize FA outcomes as attention condition lowest, demand condition lowest, and play condition lowest, according to the condition in which problem behavior is most disrupted. In Study 1, we applied this criterion to 120 datasets finding that 60% could be classified using this method, whereas 89% of datasets showed a disruption of 50% or higher. In Study 2, we conducted a treatment component analyses for 3 individuals whose FAs each exhibited one of the 3 distinct patterns. The results indicated that specific elements of the FA conditions could reduce problem behavior. The predictive utility of these disruption patterns is discussed.


Effects of thermal processing on the allergenicity, structure, and critical epitope amino acids of crab tropomyosin.
Food processing can change the structure and immunoreactivity of purified allergens, but the effect of food processing on the immunoreactivity of the processed and purified allergen is still poorly understood. In this study, tropomyosin (TM) was obtained from Scylla paramamosain and purified after different treatments. A basophil activation test was employed to detect the allergenicity of allergens. The protein structure was detected by mass spectrometry, circular dichroism spectroscopy and surface hydrophobicity. Critical amino acids were identified by Dot blot. Heating obviously affects the biochemical characteristics of TM. The allergenicity of TM was decreased in high temperature-pressure-processed crabs, due to alteration in the protein structure (e.g. denaturation). Seven critical amino acids, namely, R21, E103, E104, E115, A116, E122 and E156, related to the maintenance of the IgE-binding activity of TM were identified. This research of thermal processing helps to accurately reduce or eliminate the immunoreactivity of crabs by food processing.


Assemble CRISPRs from metagenomic sequencing data.
Clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR-Cas) allows more specific and efficient gene editing than all previous genetic engineering systems. These exciting discoveries stem from the finding of the CRISPR system being an adaptive immune system that protects the prokaryotes against exogenous genetic elements such as phages. Despite the exciting discoveries, almost all knowledge about CRISPRs is based only on microorganisms that can be isolated, cultured and sequenced in labs. However, about 95% of bacterial species cannot be cultured in labs. The fast accumulation of metagenomic data, which contains DNA sequences of microbial species from natural samples, provides a unique opportunity for CRISPR annotation in uncultivable microbial species. However, the large amount of data, heterogeneous coverage and shared leader sequences of some CRISPRs pose challenges for identifying CRISPRs efficiently in metagenomic data. In this study, we developed a CRISPR finding tool for metagenomic data without relying on generic assembly, which is error-prone and computationally expensive for complex data. Our tool can run on commonly available machines in small labs. It employs properties of CRISPRs to decompose generic assembly into local assembly. We tested it on both mock and real metagenomic data and benchmarked the performance with state-of-the-art tools. The source code and the documentation of metaCRISPR is available at https://github.com/hangelwen/metaCRISPR CONTACT: email@example.com.


[Research Progress and Application of Digital Pathology Technology in Bone Marrow Morphology].
Advances in digital pathology technology have enabled pathologists and laboratory physicians to perform quick, easy, accurate and reproducible analysis of digital images of tissues and cells with the aid of electronic screens and software tools, rather than relying solely on traditional optical microscopy observations. The conventional clinical cytology testing practice is to be replaced by a digital workflow, which includes both digital imaging and image analysis. This article provides an overview of the basic principles of digital pathology techniques, the advances of development of device in cytology digital pathology, and their clinical applications in bone marrow morphology, and existing problems and prospects of digital pathology application in hematology.


Transcriptional activation of quinoline degradation operons of Pseudomonas putida 86 by the AraC/XylS-type regulator OxoS and cross-regulation of the PqorM promoter by XylS.
The quinoline-degradative gene cluster (oxoO, open reading frames 1 to 6 [ORF1 to -6], qorMSL, ORF7 to -9, oxoR) of Pseudomonas putida 86 consists of several overlapping operons controlled in response to quinoline by the master promoter PoxoO and internal promoters Porf3, PqorM, and PoxoR. ORF7 to -9, presumed to be important for maturation of the molybdenum hydroxylase quinoline 2-oxidoreductase, are also weakly transcribed independently of quinoline. Expression of the oxoS gene, located upstream of oxoO, is not influenced by the carbon source. OxoS shows 26% amino acid sequence identity to XylS, the transcriptional regulator of the meta pathway promoter Pm of TOL plasmid pWW0, and is required for quinoline-dependent transcription from PoxoO, Porf3, PqorM, and PoxoR. 5' deletion analysis of PoxoO and PqorM suggested that a 5'-TGCPuCT-N3-GGGATA-3' motif, which resembles the distal 5'-TGCA-N6-GGNTA-3' half-site of the tandem XylS binding site, is essential for oxoS-dependent transcriptional activation. PqorM, which shows similarity to the tandem XylS recognition site of Pm, was cross-activated by the xylS gene product in response to benzoate. The distal half-site of PqorM is necessary, but probably not sufficient, for transcriptional activation by XylS. Despite conservation in PoxoO of a distal 5'-TGCA-N6-GGNTA-3' sequence, cross-activation of PoxoO by XylS and benzoate was not observed. The oxoS gene product in the presence of quinoline weakly stimulated transcription from the Pm promoter. Involvement of an XylS-type protein in the regulation of genes encoding synthesis of a molybdenum hydroxylase is without precedent and may reflect the evolutionary origin of this pathway in the metabolism of aromatic compounds.


[Morphological changes in the respiratory tract of guinea pigs exposed to kerosene aerosol].
It's well known that there exists a high correlation between daily usage of Kerosene and the appearance of dyspnea in healthy humans and in asthmatic patients. Our aim is to study the histological alterations of the respiratory tract of guinea pigs submitted to Kerosene aerosol. It was administered to male guinea pigs fifteen minutes daily for a month. Fragments of trachea and lungs were processed for histological studies. Erosion of tracheal epithelium and inflammatory infiltration were observed. Lungs presented with thickening of the interalveolar septa. The eosinophilic infiltration may represent an immunological response resembling reactions of immediate hypersensitivity. The morphological alterations may be induced by toxic products of Kerosene such as sulphur impurities that act as mucosal irritants which damage defense mechanisms of the organism.


Pyroptosis in glioblastoma: A crucial regulator of the tumour immune microenvironment and a predictor of prognosis.
Recent studies have shown that pyroptosis, an inflammatory form of cell death, has a dual role in tumorigenesis and tumour progression and affects the prognosis of patients; however, the role of pyroptosis in glioblastoma (GBM) is still unclear. In this study, based on GBM patients' data from two independent cohorts, we performed a comprehensive analysis of the expression and prognostic value of 33 pyroptosis-associated genes (PAGs) in GBM, as well as their role in the tumour immune microenvironment (TIME) of GBM. We identified 29 PAGs that were differentially expressed between GBM and normal brain tissue, 18 of which were upregulated in GBM tissue. Most of the 33 PAGs were strongly correlated with the levels of immune cell infiltration. Based on the 33 PAGs, the GBM samples can be divided into two clusters (C1-C2), with C1 having a 'hot' but immunosuppressive TIME and C2 having a 'cold' TIME, suggesting different immunotherapeutic responses in the two clusters. In addition, we identified four PAGs that were strongly associated with GBM prognosis and constructed a risk model based on these four PAGs. This risk model is an independent prognostic factor for GBM patients, and there is a different immune status between high- and low-risk groups. In conclusion, this study demonstrates that pyroptosis is closely associated with the prognosis and TIME of GBM and provides an important basis for further studies on the relationship between pyroptosis and GBM.


Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma.
Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel re-programming of transcript length between Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5' leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements of differential leader transcripts revealed nuanced transcriptional and translational regulation. One such class of regulated longer leader transcripts exhibited tight transcriptional and translational repression. Further examination of these dually repressed genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature.


Unexpected Findings During Evaluation of Acute Pelvic Pain With Transvaginal Sonography.
Transvaginal sonography is the first-line imaging modality used to evaluate acute female pelvic pain in the emergency setting because of its accessibility, lack of ionizing radiation, and excellent ability to identify reproductive tract disorders. Although the intent of transvaginal sonography is to evaluate the reproductive organs, imaging of adjacent pelvic structures is an important part of every transvaginal sonographic examination. Gastrointestinal, urologic, and vascular disorders incidentally scanned on transvaginal sonography may explain the pain for which the examination is being performed. In such cases, transvaginal sonography may play an important role in the diagnostic process if the clinician is aware of the transvaginal sonographic appearance of these entities.


No-go theorem for gaussian quantum error correction.
We prove that Gaussian operations are of no use for protecting Gaussian states against Gaussian errors in quantum communication protocols. Specifically, we introduce a new quantity characterizing any single-mode Gaussian channel, called entanglement degradation, and show that it cannot decrease via Gaussian encoding and decoding operations only. The strength of this no-go theorem is illustrated with some examples of Gaussian channels.