Treatment of keloid scars with a 1210-nm diode laser in an animal model.
A temperature increase can improve wound healing by activation of heat shock protein 70 and stimulation of fibroblasts. Since keloids are a dysfunction of collagen fiber synthesis and organization, this study aimed to evaluate if a 1,210 nm diode laser could have effects in a new animal model of keloid scars. A total of 39 nude mice were used for this study. Phototypes IV and V human keloids were grafted into their backs and after 1 month of healing, the mice were divided into four groups: Control, Laser, Resection, Resection/Laser. In the Laser group, the keloids were treated with a 1,210-nm diode-laser with the following parameters: 4 W; 10 seconds; fluence: 51 J/cm(2) ; spot: 18.9 × 3.7 mm(2) . In the Resection group, surgical intra-lesional excision was performed. In the Resection/Laser group, keloids were treated with the 1,210-nm laser-diode after surgical intra-lesional excision. Temperature measurements were made during the laser treatment. Clinical examination and histological study were performed on the day of treatment and 1 month, 2 months, and 3 months later. Mean temperature measurement was of 44.8°C (42-48°) in the Laser groups. No healing complications or keloid proliferation was observed in any group. Keloid histologic characters were confirmed in all grafts. No histologic particularity was observed in the laser groups in comparison with the Control and Resection groups. First, this keloid animal model appears to be adapted for laser study. Secondly, the 1,210-nm diode laser does not induce keloid thermal damage in vivo. Further studies with different 1,210-nm laser diode parameters should be performed in order to observe significant effects on keloids.


MEDICAL AND LEGAL ISSUES OF THE DECISIONS RENDERED BY THE EUROPEAN COURT OF HUMAN RIGHTS.
The European Convention on Human rights is a document that protects human rights and fundamental freedoms of individuals, and the European Court of Human Rights and its case-law makes a convention a powerful instrument to meet the new challenges of modernity and protect the principles of rule of law and democracy. This is important, particularly for young democracies, including Georgia. The more that Georgia is a party to this convention. Article 3 of the convention deals with torture, inhuman and degrading treatment, while article 8 deals with private life, home and correspondence. At the same time, the international practice of the European court of human rights shows that these articles are often used with regard to medical rights. The paper highlights the most recent and interesting cases from the case-law of the ECHR, in which the courts conclusions are based solely on the European Convention on Human Rights. In most instances, the European Court of Human Rights uses the principle of democracy with regard to medical rights. The European court of human rights considers medical rights as moral underpinning rights. Particularly in every occasion, the European Court of Human Rights acknowledges an ethical dimension of these rights. In most instances, it does not matter whether a plaintiff is a free person or prisoner, the European court of human rights make decisions based on fundamental human rights and freedoms of individuals.


Type 2 Diabetes and Precursors in Community Dwelling Asian Indian Adult Youth.
Recent studies have shown a high prevalence of Type-2-diabetes (T2DM) (24%) and prediabetes (18.1%) in Kerala. There is no community based study from South Asia regarding the prevalence of type 2 diabetes and its precursors in the young adult population. This community based study was done to find the prevalence of type 2 diabetes and its precursors in South Indian adult youth (18-30 years age) of Thiruvananthapuram district. Cross sectional design was used for this study. Multistage cluster sampling was used to enrol community dwelling youth of 18 to 30 years, residing in Thiruvananthapuram district. Six panchayath wards from rural and urban regions and 4 from coastal area were randomly selected as the primary sampling units. Trained staff nurses conducted the survey with the help of accredited-social-health-activists (ASHA). Socio-demographic data, anthropometry, clinical features of insulin resistance, and random capillary glucose (CG) and blood pressure were assessed and recorded. Oral Glucose tolerance test or HbA1c was done for participants with a CG ≥130 mg/dl for diagnosis of diabetes and prediabetes. A total of 1031 participants were included from the rural (n = 394), coastal (n = 269) and urban (n = 368) areas. Prevalence of hyperglycaemia i.e., T2DM and pre-diabetes was 0.48% (n = 5) and 2.4% (n = 25) respectively. Family-history of T2DM was present in 35.1% subjects. Prevalence of overweight, obesity and abdominal-obesity was 28.2%, 16.1% and 28.4% respectively. Clinical-features of insulin resistance (CFIR) were present in 27.1% subjects (acanthosis [17.7%], skin tags [1.7%] and PCOS phenotype [10.7%]). Among various anthropometric measurements and their derivatives, CFIR correlated best (r = 0.24, P < 0.01) with the product of BMI and the sum of abdominal circumference and hip circumference (Trivandrum Medical College [TMC] -adiposity-index), which is a newly proposed parameter. Hyperglycaemia was more common in males, did not correlate with waist hip ratio, and correlated best again with TMC-adiposity-index ((r = 0.13, P < 0.01). The burden of insulin resistance in the young South Indian population, hitherto unknown in any community based study, has been studied for the first time. The prevalence of precursors of T2DM is high in this population. Early identification of 'at risk' individuals could provide a window of opportunity for preventing or delaying future diabetes and its long term complications. TMC adiposity index could become a valuable tool in the anthropometric assessment for predicting future T2DM.


Sexual reproduction of the placental brooder Celleporella hyalina (Bryozoa, Cheilostomata) in the White Sea.
The evolution of parental care is a central field in many ecological and evolutionary studies, but integral approaches encompassing various life-history traits are not common. Else, the structure, development and functioning of the placental analogues in invertebrates are poorly understood. Here, we describe the life-history, sexual colony dynamics, oogenesis, fertilization and brooding in the boreal-Arctic cheilostome bryozoan Celleporella hyalina. This placental brooder incubates its progeny in calcified protective chambers (ovicells) formed by polymorphic sexual zooids. We conducted a detailed ultrastructural study of the ovary and oogenesis, and provide evidence of both auto- and heterosynthetic mechanisms of vitellogenesis. We detected sperm inside the early oocyte and within funicular strands, and discuss possible variants of fertilization. We also detail the development and functioning of the placental analogue (embryophore) in the various stages of embryonic incubation as well as embryonic histotrophic nourishment. In contrast to all known cheilostome placentas, the main part of embryophore of C. hyalina is not a single cell layer. Rather, it is a massive "nutritive tissue" whose basal part is associated with funicular strands presumably providing transport function. C. hyalina shows a mixture of reproductive traits with macrolecithal oogenesis and well-developed placenta. These features give it an intermediate position in the continuum of variation of matrotrophic provisioning between lecithotrophic and placentotrophic cheilostome brooders. The structural and developmental differences revealed in the placental analogue of C. hyalina, together with its position on the bryozoan molecular tree, point to the independent origin of placentation in the family Hippothoidae.


Spatially explicit bioaccumulation modeling in aquatic environments: Results from 2 demonstration sites.
Bioaccumulation models quantify the relationship between sediment and water exposure concentrations and resulting tissue levels of chemicals in aquatic organisms and represent a key link in the suite of tools used to support decision making at contaminated sediment sites. Predicted concentrations in the aquatic food web provide exposure estimates for human health and ecological risk assessments, which, in turn, provide risk-based frameworks for evaluating potential remedial activities and other management alternatives based on the fish consumption pathway. Despite the widespread use of bioaccumulation models to support remedial decision making, concerns remain about the predictive power of these models. A review of the available literature finds the increased mathematical complexity of typical bioaccumulation model applications is not matched by the deterministic exposure concentrations used to drive the models. We tested a spatially explicit exposure model (FishRand) at 2 nominally contaminated sites and compared results to estimates of bioaccumulation based on conventional, nonspatial techniques, and monitoring data. Differences in predicted fish tissue concentrations across applications were evident, although these demonstration sites were only mildly contaminated and would not warrant management actions on the basis of fish consumption. Nonetheless, predicted tissue concentrations based on the spatially explicit exposure characterization consistently outperformed conventional, nonspatial techniques across a variety of model performance metrics. These results demonstrate the improved predictive power as well as greater flexibility in evaluating the impacts of food web exposure and fish foraging behavior in a heterogeneous exposure environment. Integr Environ Assess Manag 2017;13:1023-1037. © 2017 SETAC.


Value of endoscopy and MRI for predicting intestinal surgery in patients with Crohn's disease in the era of biologics.
Severe endoscopic lesions (SEL) in patients with colonic Crohn's disease (CD) have been linked to higher risk of colectomy. The aims of this study were to reassess the predictive value of colonoscopy compared against MRI for requirement of resection surgery in patients with CD and determine the influence of current therapeutic options. In this single-centre, observational, prospective, longitudinal study, patients with an established diagnosis of CD and suspected activity were included. After baseline assessment, including colonoscopy and MRI, patients were followed until resection surgery or the end of study. 112 patients were eligible for analysis. Ulcers were present in 94/112 (84%) of patients at colonoscopy (SELs in 51/112 (46%)) and stenosis in 38/112 (34%). MRI identified ulcers in 79/112 (71%) of patients, stenosis in 36/112 (32%) and intra-abdominal fistulae in 20/112 (18%). Surgical resection requirements (29/112 (26%)) were not associated with the presence of SELs at colonoscopy. The presence of stenosis (p<0.001) or intra-abdominal fistulae (p<0.001) at MRI correlated with a higher risk of surgery. In the multivariate analysis, perianal disease (OR 9 (2 to 39), p=0.003), stenosis (OR 3.4 (1 to 11), p=0.04) and fistulae at MRI (OR 10.6 (2 to 46), p=0.002) increased the risk of abdominal resection surgery, while months under immunomodulators (OR 0.94 (0.90 to 0.98), p=0.002) and/or antitumor necrosis factor (anti-TNF) therapy (OR 0.97 (0.94 to 1), p=0.04) during follow-up decreased this risk. Perianal disease, stenosis and/or intra-abdominal fistulae at MRI independently predict an increased risk of resection surgery in patients with CD, whereas immunosuppressants and/or anti-TNF therapy reduce such risk. Under current therapeutic strategies, the presence of SELs is not a predictor of resection surgery in patients with CD.


Efficacy of Intravenous Immunoglobulins against Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids: A Case Report.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disease of the central nervous system that predominantly affects the brainstem. Apart from corticosteroids, there are few reported treatment options for CLIPPERS, and there is no standard therapy. A 77-year-old man presented with diplopia that had persisted for 5 months. Dysarthria and numbness of the distal right upper extremity and right lips were also observed. Brain magnetic resonance imaging (MRI) revealed a hyperintense area around the brainstem. Symptoms were relieved immediately following intravenous methylprednisolone (IVMP) administration. However, after gradual tapering of oral prednisolone to 5 mg/day, the symptoms relapsed, and brain imaging revealed that the condition had worsened. Intravenous immunoglobulins (IVIg) were administered for recurrence, with no clinical improvement. After each IVMP treatment, the patient recovered promptly. Based on the patient's symptoms and characteristic MRI findings, exclusion of other diseases, and the significant efficacy of corticosteroids, he was diagnosed with CLIPPERS. There was no recurrence at a maintenance prednisolone dose of 8 mg/day. IVIg had a poor effect on the acute phase of CLIPPERS symptoms. Compared with other immunosuppressants, IVIg is less effective in suppressing the relapse of CLIPPERS.


Update on childhood and adolescent immunizations: selected review of US recommendations and literature: part 1.
To provide a clinically relevant synopsis of research findings regarding childhood and adolescent vaccines. Much research confirms the safety, immunogenicity, and efficacy of specific vaccines as well as the positive impact on overall morbidity and mortality. Prevention and control strategies involve the expansion of vaccine recommendations to include more individuals and/or more vaccine doses. In addition, the role of universal infant vaccination, the advantages of even partial immunization, and the documented benefits of recently introduced vaccines are explored. The material in this review includes important areas of clinical practice improvement, such as awareness of interim recommendations or monitoring of vaccine failures. Literature on hepatitis B, rotavirus, Haemophilus influenzae type b conjugate, and pneumococcal vaccines is included in this first of two articles. New research on childhood and adolescent vaccines is anticipated to shape the practice of pediatric providers. Research will continue to provide the science to optimize protection and to promote the health and well being of all children and adolescents.


Pharmacokinetic and pharmacodynamic evaluation of intramuscular artesunate in healthy beagle dogs.
Pharmacokinetic and pharmacodynamic responses were evaluated after intramuscular (i.m.) injection of artesunate (AS). Twelve dogs were injected with i.m. AS at 2.5, 5, or 10 mg/kg into the left gluteal muscle. A second injection of only diluent was given in the right gluteal muscle. At 24 hours post-injection, plasma creatine kinase (CK) concentrations were elevated above normal. Muscle biopsies showed myocyte necrosis and acute inflammation, which was worse on the treated side. At 7 days after injection, CK concentrations were normal. Muscle biopsies showed mineralization, fibrosis, and chronic inflammation with less difference between sides. Compared with intravenous administration, i.m. AS resulted in a prolonged half-life for both AS and DHA. Intramuscular AS also had a lower mean dose-adjusted C(max) and a higher mean dose-adjusted area under the curve; but produced similar concentrations of dihydroartemisinin. These findings suggest that adverse reactions to i.m. artesunate are minor and temporary which justify further study of this route in treating severe malaria.


A highly selective and sensitive fluorescent thiol probe through dual-reactive and dual-quenching groups.
A new fluorescent probe installed with dual-reactive and dual-quenching groups was rationally designed for highly selective and sensitive sensing of biothiols. The sensitivity of the probe toward thiols was significantly improved by dual-quenching effects. Furthermore the selectivity of the probe was also greatly enhanced by installation of dual-reactive groups.


[Mature teratoma in the posterior mediastinum showing the fatty density on the chest computed tomography].
We reported a case of posterior mediastinal mature teratoma. A 16-year-old woman was referred for further investigation of a left paravertebral mass detected on chest roentgenogram. The defined mass was located above the diaphragm and showed homogeneous fat density on computed tomography (CT) and hypersignal intensity on both T1 weighted images and T2 weighted images on magnetic resonance imaging (MRI). Radiologically, there was a mimicking foci of calcification. The mass was histologically diagnosed as mature teratoma.


Players over the Surface: Unraveling the Role of Exopolysaccharides in Zinc Biosorption by Fluorescent Pseudomonas Strain Psd.
Fluorescent Pseudomonas strain Psd is a soil isolate, possessing multiple plant growth promoting (PGP) properties and biocontrol potential. In addition, the strain also possesses high Zn2+ biosorption capability. In this study, we have investigated the role exopolysaccharides (EPS) play in Zn2+ biosorption. We have identified that alginates are the prime components contributing to Zn2+ biosorption. Deletion of the alg8 gene, which codes for a sub-unit of alginate polymerase, led to a significant reduction in EPS production by the organism. We have also demonstrated that the increased alginate production in response to Zn2+ exposure leads to improved biofilm formation by the strain. In the alg8 deletion mutant, however, biofilm formation was severely compromised. Further, we have studied the functional implications of Zn2+ biosorption by Pseudomonas strain Psd by demonstrating the effect on the PGP and biocontrol potential of the strain.


Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride.
Prophylaxis or therapy with a combination of a neurokinin 1 (NK-1) receptor antagonist (RA), a 5-hydroxytryptamine- 3 (5-HT3) RA, and dexamethasone is recommended by international antiemesis guidelines for the prevention of chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy and for select patients receiving moderately emetogenic chemotherapy. VARUBI (rolapitant) is a substance P/NK-1 RA that was recently approved by the U.S. Food and Drug Administration as an injectable emulsion in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Granisetron Hydrochloride Injection USP is one of the 5-HT3 RAs indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Herein, we describe the physical and chemical compatibility and stability of VARUBI (rolapitant) injectable emulsion (166.5 mg/92.5 mL [1.8 mg/mL], equivalent to 185 mg of rolapitant hydrochloride) admixed with Granisetron Hydrochloride Injection USP (1.0 mg/mL, equivalent to 1.12 mg/mL hydrochloride). Binary admixtures of VARUBI injectable emulsion and Granisetron Hydrochloride Injection USP were prepared and stored in VARUBI ready-to-use glass vials and in four types of commonly used intravenous administration (tubing) sets. Evaluation of the physical and chemical compatibility and stability of the admixtures in the VARUBI ready-to-use vials stored at room temperature (20°C to 25°C) under fluorescent light and under refrigeration (2°C to 8°C protected from light) was conducted at 0, 1, 6, 24, and 48 hours, and that of the admixtures in the intravenous tubing sets was evaluated at 0, 2, and 6 hours of storage at 20°C to 25°C. Physical stability was evaluated by visual examination of the container contents under normal room light, and measurement of turbidity, globule size, and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations (potency) and impurity levels by high-performance liquid chromatographic analysis. The pH, turbidity, globule size, and particulate matter of all samples remained within narrow and acceptable ranges at all study time points, indicating that combining the two formulations into a binary admixture is physically and chemically compatible and stable. VARUBI injectable emulsion admixed with Granisetron Hydrochloride Injection USP demonstrated compatibility and stability in a ready-to-use glass vial for at least 24 hours at room temperature and 48 hours under refrigeration, as well as in the four intravenous tubing sets for at least 6 hours at 20°C to 25°C. No decrease of drug concentration (or potency) of any admixed components occurred in the samples stored at the two conditions and time periods studied based on high-performance liquid chromatographic analysis. The levels of impurities stayed below the safety limits set by International Conference on Harmonisation during the study period.


Transitional metaplasia in intestinal epithelium of rats submitted to intestinal cystoplasty and treatment with L -lysine.
To evaluated the effects of L-lysine on the intestinal and urothelial epithelia in cystoplasty in rats. Twenty-eight 9-week-old rats were assigned to 4 groups: Group A (n=8) cystoplasty followed by administration of L-lysine (150 mg/kg body weight by gavage) for 30 weeks; Group B (n=8) cystoplasty + water for 30 weeks; Group C (n=6) L-lysine for 30 weeks; Group D (n=6) water for 30 weeks. On histopathology with hematoxylin and eosin, mild to moderate hyperplasia transitional was observed in at the site of anastomosis in all animals submitted to cystoplasty (Groups A and B), but "transitional metaplasia" of the intestinal glandular epithelium was more accentuated in Group A (p=0.045). No inflammatory cells, dysplasia or abnormalities were observed. Staining with Alcian blue revealed a substantial reduction of goblet cells and mucins in the colon segment (Groups A and B). The administration of L-lysine to rats accelerated the development of transitional metaplasia in the epithelium of the colon segment in cystoplasty.


Galvanic Bipolar Electrode Arrays with Self-Driven Optical Readouts.
In this work, we report a bipolar electrode (BPE) array system with self-driven optical readouts of the faradic current flowing through the BPEs. The BPE array system is based on the spontaneous redox reactions that are respectively occurring at opposite poles of the BPEs with appropriate electrocatalysts on the poles; this system is analogous to one consisting of galvanic electrochemical cells. The galvanic BPE array system operates in a self-powered mode that requires there to be neither a direct electrical connection nor external electrical polarization to each BPE. Importantly, the appropriate electrocatalysts on the poles play a critical role in the galvanic BPE array system to induce the spontaneous redox reactions occurring at the poles of BPEs. Moreover, the galvanic BPE array system provides self-driven optical readouts, including fluorometric and colorimetric ones, to report the faradaic current resulting from the spontaneous redox reactions on the BPE poles. Based on the unique benefits that the galvanic BPE array system has over conventional BPEs, we demonstrated the promising potential of galvanic BPE arrays for the simple yet rapid and quantitative screening of electrocatalysts for the oxygen reduction reaction as well as sensitive sensing of H2O2 in parallel.


[Dose reconstruction using respiratory signals and machine parameters during treatment in stereotactic body radiotherapy].
Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. The purpose of this study was to reconstruct the dose distribution from respiratory signals and machine parameters acquired during stereotactic body radiotherapy (SBRT). The treatment plans created for VMAT-SBRT included the constraint of 1 mm/degree in multileaf collimator (MLC) for a moving phantom and three patients with lung tumors. The respiratory signals were derived from projection images acquired during VMAT delivery, while the machine parameters were derived from machine logs. The respiratory signals and machine parameters were then linked along with the gantry angle. With this data, the dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4D CT). The doses at the isocenter, the point of max dose and the centroid of the target were compared with those of the corresponding plans. In the phantom study, the maximum dose difference between the plan and "in-treatment" results was -0.4% at the centroid of the target. In the patient study, the difference was -1.8 ± 0.4% at the centroid of the target. Dose differences of the evaluated points between 4 and 10 phases were not significant. The present method successfully reconstructed the dose distribution using the respiratory signals and machine parameters acquired during treatment. This is a feasible method for verifying the actual dose for a moving target.


Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications.
Leptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders.


Local microwave hyperthermia in the treatment of benign prostatic hypertrophy.
Local deep microwave hyperthermia has been introduced recently for the treatment of benign prostatic hypertrophy (BPH). We report the results of treatment in 114 patients divided into 2 groups. The first group included 83 patients with severe obstructive symptoms. Although some improvement was found in the scoring of both subjective and objective parameters, the number of patients benefiting was small, with only 28% showing improvement in both parameters. Approximately 50% reported subjective improvement but in only 25% was this significant. In 42% there was objective evidence of improvement. Prostatic volumes did not change as a result of treatment. The second group comprised 31 patients with indwelling catheters because of acute urinary retention. After treatment, 19 patients (61%) were able to dispense with the catheter. The difficulties of interpreting an open trial of treatment for BPH and assessing its impact on objective parameters and symptomatology are discussed. Our results should be regarded cautiously in view of these reservations.


Isolation of a new foamy retrovirus from orangutans.
We have isolated a new foamy virus from blood samples taken from two apparently healthy orangutans (Pongo pygmaeus). The older orangutan has since died with encephalopathy after a brief acute illness, while the younger one, his grandson, remains well. These animals and 12 other orangutans had specific antibodies to foamy virus as measured by immunofluorescence. The new foamy virus and the antisera showed strong and specific neutralization, with only weak cross-reaction with other simian foamy virus strains. Southern blotting with gag and env probes of human foamy virus and PCR amplification showed that the new foamy virus, designated SFV-11, is related to, yet distinct from, previously characterized strains from humans, chimpanzees, and monkeys.


Numerical study on electronic and optical properties of organic light emitting diodes.
In this paper, we present a finite element method (FEM) study of space charge effects in organic light emitting diodes. Our model includes a Gaussian density of states to account for the energetic disorder in organic semiconductors and the Fermi-Dirac statistics to account for the charge hopping process between uncorrelated sites. The physical model cover all the key physical processes in OLEDs, namely charge injection, transport and recombination, exciton diffusion, transfer and decay as well as light coupling, and thin-film-optics. The exciton model includes generation, diffusion, and energy transfer as well as annihilation. We assumed that the light emission originates from oscillating and thus embodied as excitons and embedded in a stack of multilayer. The out-coupled emission spectrum has been numerically calculated as a function of viewing angle, polarization, and dipole orientation. We discuss the accumulation of charges at internal interfaces and their signature in the transient response as well as the electric field distribution.


Influence of technical processing units on polyphenols and antioxidant capacity of carrot (Daucus carrot L.) juice.
The effect of three processing units (blanching, enzyme liquefaction, and pasteurisation) on polyphenols and antioxidant activity of carrot juices was investigated. Polyphenols and antioxidant activity of carrot juices varied with different processes. Five polyphenolic acids were identified in fresh carrot juice, and the predominant compound was chlorogenic acid. Compared with fresh carrot juice, blanching and enzyme liquefaction could result in the increase of the total polyphenol content (TPC) and the antioxidant activity in scavenging DPPH free radicals (DPPH) and Fe(2+)-chelating capacity (FC), whereas pasteurisation could result in the decrease of the TPC and the antioxidant activity in DPPH and FC. Meanwhile blanching, enzyme liquefaction, and pasteurisation showed little influence on the antioxidant activity in lipid peroxidation protection. The antioxidant activities in DPPH and FC increased with increasing concentration while no correlation between lipid peroxidation protection and polyphenols concentration. Polyphenols still retained high antioxidant activity after the processes, which have potential health benefits for consumers.


Proteolytic cleavages of MET: the divide-and-conquer strategy of a receptor tyrosine kinase.
Membrane-anchored full-length MET stimulated by its ligand HGF/SF induces various biological responses, including survival, growth, and invasion. This panel of responses, referred to invasive growth, is required for embryogenesis and tissue regeneration in adults. On the contrary, MET deregulation is associated with tumorigenesis in many kinds of cancer. In addition to its well-documented ligand-stimulated downstream signaling, the receptor can be cleaved by proteases such as secretases, caspases, and calpains. These cleavages are involved either in MET receptor inactivation or, more interestingly, in generating active fragments that can modify cell fate. For instance, MET fragments can promote cell death or invasion. Given a large number of proteases capable of cleaving MET, this receptor appears as a prototype of proteolytic-cleavage-regulated receptor tyrosine kinase. In this review, we describe and discuss the mechanisms and consequences, both physiological and pathological, of MET proteolytic cleavages. [BMB Reports 2019; 52(4): 239-249].


Regulation of urease expression of Actinomyces naeslundii in biofilms in response to pH and carbohydrate.
The hydrolysis of urea by the urease enzymes of oral bacteria is believed to have a major impact on oral microbial ecology and to be intimately involved in oral health and diseases. Actinomyces naeslundii is a ureolytic bacterium that is adapted to tolerate the rapid and dramatic fluctuations in nutrient availability, carbohydrate source, and pH in dental biofilms. Our research objectives were to better understand the regulation of the expression of urease under environmental conditions that closely mimic those in dental biofilms. A. naeslundii ATCC12104 were grown in a chemostat biofilm reactor with carbohydrate-limited medium for 3 days followed by a carbohydrate pulse, at pH 7.0 and at pH 5.5. Urease activities and ureC gene messenger RNA levels of cells in the biofilm were measured before and after the carbohydrate pulse. We found that the neutral pH environments and excess carbohydrate availability could both result in enhancement of urease activity in biofilm cells. The ureC messenger RNA level of A. naeslundii biofilm cells cultivated at pH 7.0 was approximately 10-fold higher than that of cells grown at pH 5.5, but no changes in ureC gene expression were detected after the carbohydrate pulse. Neutral pH environments and excess carbohydrate availability could promote urease expression of A. naeslundii in biofilms, but only neutral pH environments could up-regulate the ureC gene expression and the pH regulates ureC gene expression at a transcriptional level.


Development of a new RF coil and gamma-ray radiation shielding assembly for improved MR image quality in SPECT/MRI.
Magnetic resonance (MR)-based multimodality imaging systems, such as single-photon emission tomography (SPECT)/magnetic resonance imaging (MRI) or positron emission tomography (PET)/MRI, face many difficulties because of problems with the compatibility of the nuclear detector system with the MR system. However, several studies have reported on the design considerations of MR-compatible nuclear detectors for combined SPECT/MRI. In this study, we developed a new radiofrequency (RF) coil and gamma-ray radiation shielding assembly to advance the practical implementation of SPECT/MRI in providing high sensitivity while minimizing the interference between the MRI and SPECT systems. The proposed assembly consists of a three-channel receive-only RF coil and gamma-ray radiation shields made of a specialized lead composite powder designed to reduce conductivity and thus minimizing any effect on the magnetic field arising from the induced eddy currents. A conventional birdcage RF coil was also tested for comparison with the proposed RF coil. Quality (Q)-factors were measured using both RF coils without any shielding, with solid lead shielding, and with our composite lead shielding. Signal-to-noise ratios (SNRs) were calculated using 4 T MR images of phantoms both with and without the new gamma-ray radiation shields. The Q-factor and SNR measurements demonstrate the improved MRI performance due to the new RF coil/gamma-ray radiation shield assembly designed for SPECT/MRI, making it a useful addition to multimodality imaging technology not only for animal studies but also for in vivo study of humans.


Sleep Disturbances in Autoimmune Neurologic Diseases: Manifestation and Pathophysiology.
Autoimmune neurologic diseases are a new category of immune-mediated disease demonstrating a widely varied spectrum of clinical manifestations. Recently, sleep disturbances in patients with autoimmune neurologic diseases have been reported to have an immense negative impact on the quality of life. Excessive daytime sleep, rapid eye movement sleep behavior disorder (RBD), and narcolepsy are the most frequent sleep disorders associated with autoimmune neurologic diseases. Sleep disturbances might be the initial symptoms of disease or persist throughout the course of the disease. In this review, we have discussed sleep disturbances in different autoimmune neurologic diseases and their potential pathophysiological mechanisms.


Relative Deprivation, Income Inequality, and Cardiovascular Health: Observational and Mendelian Randomization Studies in Hong Kong Chinese.
The associations between absolute vs. relative income at the household or neighborhood level and cardiovascular disease (CVD) risk remain understudied in the Chinese context. Further, it is unclear whether stress biomarkers, such as cortisol, are on the pathway from income to CVD risk. We examined the associations of absolute and relative income with CVD risk observationally, as well as the mediating role of cortisol, and validated the role of cortisol using Mendelian Randomization (MR) in Hong Kong Chinese. Within Hong Kong's FAMILY Cohort, associations of absolute and relative income at both the individual and neighborhood levels with CVD risk [body mass index (BMI), body fat percentage, systolic blood pressure, diastolic blood pressure, self-reported CVD and self-reported diabetes] were examined using multilevel logistic or linear models (n = 17,607), the mediating role of cortisol using the mediation analysis (n = 1,562), and associations of genetically predicted cortisol with CVD risk using the multiplicative generalized method of moments (MGMMs) or two-stage least squares regression (n = 1,562). In our cross-sectional observational analysis, relative household income deprivation (per 1 SD, equivalent to USD 128 difference in Yitzhaki index) was associated with higher systolic blood pressure (0.47 mmHg, 95% CI 0.30-0.64), but lower BMI (-0.07 kg/m2, 95% CI -0.11 to -0.04), independent of absolute income. Neighborhood income inequality was generally unrelated to CVD and its risk factors, nor was absolute income at the household or neighborhood level. Cortisol did not clearly mediate the association of relative household income deprivation with systolic blood pressure. Using MR, cortisol was unrelated to CVD risk. Based on our findings, relative household income deprivation was not consistently associated with cardiovascular health in Hong Kong Chinese, nor were neighborhood income inequality and absolute income, highlighting the context-specific ways in which relative and absolute income are linked to CVD risk.


Harmonic analysis of peripheral pulse for screening subjects at high risk of diabetes.
Power spectral density (PSD) of peripheral pulses in human has been investigated in the past for its clinical applications. Continuing the efforts, data acquired using Peripheral Pulse Analyser in research projects sponsored by Board of Research in Nuclear Sciences in 207 control subjects, 18 descendants of diabetic patients and 22 patients with systemic hypertension have been subjected to PSD analysis for its study of harmonics. Application software, named Pulse Harmonic Analyser specifically developed for this work, selected 131,072 samples from each data file, obtained PSD, derived 52 PHA parameters and saved them in an Excel sheet. Coefficient of variation in control data was reduced significantly by application of Central Limit Theorem, which enabled use of parametric methods for statistical analysis of the observations. Data in hypertensive patients have shown significant difference in comparison to that of controls in eight parameters at low values of α and β. Data in offspring of diabetic patients also have shown significant difference in one parameter indicating its usefulness in screening subjects with genetic disposition of acquiring Type-II Diabetes. PHA analysis has also yielded sub-harmonic components, which are related to combined variability in the heart rate, pulse volume and pulse morphology and has a potential to become method of choice for real time variability monitoring.


Goldberg-Shprintzen syndrome: report of a new family and review of the literature.
In 1981, Goldberg and Shprintzen described siblings with short-segment Hirschsprung disease, cleft palate, microcephaly, mild mental retardation, short stature and distinctive facial appearance. There have been several subsequent reports which broaden the phenotype. This paper describes a further family, reviews the literature and stresses the intra-familial variability.


[Influence of the angle between the nasal cavity axis and nosepiece in acoustic rhinometry].
We evaluated the influence of the angle between the nasal cavity axis and the nosepiece (made with acrylics) in acoustic rhinometry (AR). This study was composed of three experiments. In the first experiment, the influence of angulation on nasal volume was evaluated using a silicone nasal model based on a cast of the nasal cavity of a cadaver. The angle between the nosepiece and the horizontal plane was changed by 10 degrees, 40 degrees or 70 degrees, vertically; the angle between the nosepiece and the sagittal plane was similarly changed horizontally. The nasal volume, obtained as the AR area-distance curve from 6.9-14.1cm, was measured under each condition. While the horizontal change in angle did not significantly influence the result obtained by AR, in the vertical change, the measured value rose as the angle was decreased from 70 degrees to 10 degrees. In the second experiment, an evaluation in healthy subjects (5 males, 4 females, mean age 28.6 years) revealed the same tendency in changing the horizontal angle, whereas vertically a change of 10 degrees produced a significant decrease over that seen with angles of 40 degrees and 70 degrees. This result contradicted that obtained in the model study mentioned above. In studying the effect of changing the vertical angle, the volume of the posterior 5 cm and that of the anterior 2 cm of the nasal cavity was evaluated in the same subjects. The volume of the posterior 5 cm did not differ significantly among angles, while that of the anterior 2 cm showed the same trend as observed with the whole nasal cavity.(ABSTRACT TRUNCATED AT 250 WORDS)


GSH-Responsive and Hypoxia-Activated Multifunctional Nanoparticles for Synergetically Enhanced Tumor Therapy.
The integration of reactive oxygen species (ROS)-based chemodynamic therapy (CDT) and photodynamic therapy (PDT) has attracted enormous attention for synergistic antitumor therapies. However, the strategy is severely hampered by tumor hypoxia and overproduced antioxidant glutathione (GSH) in the tumor microenvironment. Inspired by the concept of metal coordination-based nanomedicines, we proposed an effective strategy for synergistic cancer treatment in response to the special tumor microenvironmental properties. Herein, we present novel metal-coordinated multifunctional nanoparticles (NPs) by the Cu2+-triggered assembly of photosensitizer indocyanine green (ICG) and hypoxia-activated anticancer prodrug tirapazamine (TPZ) (Cu-ICG/TPZ NPs). After accumulating within tumor sites via the enhanced permeability and retention (EPR) effect, the Cu-ICG/TPZ NPs were capable of triggering a cascade of combinational therapeutic reactions, including hyperthermia, GSH elimination, and Cu+-mediated •OH generation and the subsequent hypoxia-triggered chemotherapeutic effect of TPZ, thus achieving synergistic tumor therapy. Both in vitro and in vivo evaluations suggested that the multifunctional Cu-ICG/TPZ NPs could realize satisfactory therapeutic efficacy with excellent biosafety. These results thus suggested the great potential of Cu-ICG/TPZ NPs to serve as a metallodrug nanoagent for synergetically enhanced tumor treatment.


Prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service.
The purpose of this study was to determine the prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service. One hundred patients were administered the Executive Interview (EXIT25), the Executive Clock Drawing Task (CLOX), and the Mini-Mental State Examination at admission and discharge. Fifty-two percent of the patients at admission and 56% at discharge had scores indicating impairment on at least one measure of executive function. Median scores on every measure improved during hospitalization. Older patients and those with a cardiac or gastrointestinal disorder were more likely to have executive impairment. The prevalence of executive impairment on general medicine services is high. Although improvement in executive function occurs during hospitalization, many patients remained impaired.


The actin cytoskeleton and signaling network during pollen tube tip growth.
The organization and dynamics of the actin cytoskeleton play key roles in many aspects of plant cell development. The actin cytoskeleton responds to internal developmental cues and environmental signals and is involved in cell division, subcellular organelle movement, cell polarity and polar cell growth. The tip-growing pollen tubes provide an ideal model system to investigate fundamental mechanisms of underlying polarized cell growth. In this system, most signaling cascades required for tip growth, such as Ca(2+)-, small GTPases- and lipid-mediated signaling have been found to be involved in transmitting signals to a large group of actin-binding proteins. These actin-binding proteins subsequently regulate the structure of the actin network, as well as the rapid turnover of actin filaments (F-actin), thereby eventually controlling tip growth. The actin cytoskeleton acts as an integrator in which multiple signaling pathways converge, providing a general growth and regulatory mechanism that applies not only for tip growth but also for polarized diffuse growth in plants.


Oral Cavity Squamous Cell Carcinoma Presenting as an Isolated Nasal Mass in the Setting of a Fixed Implant-Supported Upper Denture.
Proper staging and diagnosing of mucosal head and neck cancers is necessary given important differences in tumor behaviors that lead to different standards of treatment. We report the unusual case of a 65-year-old woman who is a former smoker with an implant-supported upper denture who developed an isolated nasal mass on examination, which was confirmed after resection to be a squamous cell carcinoma originating from the hard palate. Although this is a rare scenario, an oral cavity cancer should be taken into consideration in the differential diagnosis of a nasal cavity mass in the setting of a fixed upper dental implant.


The governance of traditional medicine and herbal remedies in the selected local markets of Western Kenya.
A lot of emphasis is often placed on modern governance systems and little or no attention is given to traditional governance practices which remain largely undocumented. The study aimed at finding out important traditional and modern governance practices that regulate traditional medicine sector in Western Kenya. The study was carried out in selected market centres of Western Kenya where the identified traditional medicine practitioners (TMPs) sell their traditional medicine. All consenting TMPs and professional experts were interviewed with the aid of a semi-structured questionnaire. Purposive sampling design with elements of snowball techniques was employed in tracing competent traditional medicine (TM) experts and relevant professional experts. The data collected was processed in Microsoft Excel and descriptive statistics performed. Pearson's chi-square statistics was carried out to determine the significance of the traditional and modern governance data sets using the STATA software. Modern governance practices were not significantly different in all the market centres surveyed (p = 0.080). Equally, the traditional governance practices were also not significantly different in all the selected market centres (p = 1.000). Traditional governance practices play an important role in the governance of traditional medicine and are shaped by the socio-cultural beliefs of the local communities. Modern governance practices, on the other hand, are widely perceived as top downregulation of the traditional medicine growing industry.


Olfactory Dysfunction in Children: A Scoping Review.
Olfactory disorders are well-studied in the adult population, however, there is a paucity of literature characterizing olfactory dysfunction in pediatric patients. The purpose of this scoping review was to identify known causes of olfactory loss in pediatric populations, clarify the extent of use and validity of smell tests, and summarize current therapies for olfactory loss. PubMed, Ovid MEDLINE, and Web of Science. Databases were systematically searched in September 2020. Two independent reviewers conducted the title and abstract screen, followed by review of full-texts for inclusion based on preset inclusion and exclusion criteria. Extracted data included study type, age/age-range of participants, gender, radiological evidence of olfactory dysfunction, types and results of smell tests used, etiology of olfactory loss, and therapies employed for olfactory loss. A total of 103 articles (n = 1654) were eligible for final data extraction. The University of Pennsylvania Smell Identification Test was used most frequently for smell testing (21% of studies). In total, 45 causes of olfactory dysfunction have been elucidated by this study: 22 congenital and 23 acquired. Few therapies were described, and all were specific to the etiology of olfactory loss. Olfactory dysfunction has a wide range of etiologies in the pediatric population, and clinicians should have a diagnostic algorithm for how to identify a cause should they encounter it in practice. If no etiology can be identified, education around safety should be provided to both the patient and their caregivers.


Data standards are back seat drivers! Methodology for incorporating information quality into quality assurance project plans.
Quality assurance project plans for environmental data collections consider user requirements for the measurements and express these in the form of data quality objectives. User requirements now may include capture of measurements and associated information in prescribed formats to facilitate entry into computerized information systems. Establishing ahead of time that the data requirements may be an important "back seat driver" for an environmental collection effort can save considerable resources for an organization. Also, the planning may need to accommodate unique requirements associated with the entry of data into data collection systems.


Chemical probes for higher-order structure in RNA.
Three chemical reactions can probe the secondary and tertiary interactions of RNA molecules in solution. Dimethyl sulfate monitors the N-7 of guanosines and senses tertiary interactions there, diethyl pyrocarbonate detects stacking of adenosines, and an alternate dimethyl sulfate reaction examines the N-3 of cytidines and thus probes base pairing. The reactions work between 0 degrees C and 90 degrees C and at pH 4.5--8.5 in a variety of buffers. As an example we follow the progressive denaturation of yeast tRNAPhe terminally labeled with 32P as the tertiary and secondary structures sequentially melt out. A single autoradiograph of a terminally labeled molecule locates regions of higher-order structure and identifies the bases involved.


Ro 18-5364, a potent new inhibitor of the gastric (H+ + K+)-ATPase.
The sulfoxide agent Ro 18-5364 is an extremely potent and rapid inhibitor of the gastric mucosal (H+ + K+)-ATPase with an apparent Ki of 0.1 microM at pH 6. The inhibition of both enzymatic activity and vesicular proton transport in membrane preparations is concentration- and time-dependent. Comparative studies with the two enantiomers of Ro 18-5364 indicated no enantiomeric preference. Marked differences were seen between Ro 18-5364 (sulfoxide) and Ro 18-5362 (sulfide) with regard to inhibitory activity. Even at concentrations as high as 0.1 mM Ro 18-5362 failed to affect significantly (H+ + K+)-ATPase activity and associated proton translocation. Similarly, Ro 17-5380 demonstrated an apparent Ki of 20 microM for inhibition of the (H+ + K+)-ATPase whereas its reduced derivative Ro 17-4749 was inactive. Addition of a single methyl group in the pyridine moiety of Ro 18-5364 noticeably decreased the inhibitory potency. The inhibitory action of Ro 18-5364 on (H+ + K+)-ATPase activity was markedly higher at low incubation medium pH in comparison to physiological or alkaline values. The results of incorporation studies paralleled that of enzymatic inhibition. The extent of Ro 18-5364 incorporation was dependent on time, concentration, and medium hydrogen ion concentration, with a decrease in medium pH resulting in increased binding. While ATP and GTP had little effect on the binding rates, reduced lipoic acid methyl ester, mercaptoethanol and dithiothreitol were capable of displacing the radiolabel to different extents. Autoradiography of electrophoresed Ro-18-5364-labeled gastric microsomal membranes confirmed that the radiolabel was associated with polypeptides of approximately 100 kDa. The incorporation was reversed upon subjection of the membranes to reducing conditions.


Metal accumulation from contaminated food and its effect on growth of juvenile landsnails Helix engaddensis.
Metal accumulation by juvenile landsnails, Helix engaddensis, and its effect on growth rate was studied over a 5-week period of exposure and 2 weeks of recovery. An artificial food contaminated with Cu (4-2500 microg x g(-1)), Cd (50-800 microg x g(-1)), Pb, and Zn (20-12500 microg x g(-1)) was used. During the 7 weeks of the experiment, mortality rates were 20, 27, 30, and 38% among snails fed Cu-, Pb-, Zn-, and Cd-contaminated food, respectively. According to the ability to inhibit growth, metals were found to have the following order: Cd > Zn > Cu = Pb. Inhibitory effects of dietary metals started to be significant from the third week of exposure on. Inhibition of growth by Pb and Cu was found to be reversible, and within the first week of recovery, snails erupted their aestivation and resumed feeding and growth to gain weights similar to those of the control groups. Snails fed Cd- or Zn-contaminated food failed to resume growth during the 2 weeks of recovery. This indicates that in the case of Cu and Pb, growth inhibition was mainly due to starvation due to food rejection and aestivation. On the other hand, growth inhibition caused by Cd and Zn may have been resulting from irreversible toxicity. Therefore, snails were assumed to be sensitive to Cd and Zn but tolerant to Cu and Pb. Accumulation of Cu and Pb was significant only at the highest concentrations. At low and medium concentrations, no signs of accumulation were observed, indicating regulation at these concentrations. Cd and Zn accumulation starts at low concentrations but became significant at medium and high levels indicating accumulation of these metals.


Responses of deciduous broadleaf trees to defoliation in a CO2 enriched atmosphere.
Relatively little is known about the implications of atmospheric CO2 enrichment for tree responses to biotic disturbances such as folivory. We examined the combined effects of elevated CO2 concentration ([CO2]) and defoliation on growth and physiology of sugar maple (Acer saccharum Marsh.) and trembling aspen (Populus tremuloides Michx.). Seedlings were planted in the ground in eight open-top chambers. Four chambers were ventilated with CO2-enriched air (ambient + 283 micromol mol-1) and four chambers were supplied with ambient air. After 6 weeks of growth, half of the leaf area was removed on a subset of seedlings of each species in each CO2 treatment. We monitored subsequent biomass gain and allocation, along with leaf gas exchange and chemistry. Defoliation did not significantly affect final seedling biomass in either species or CO2 treatment. Growth recovery following defoliation was associated with increased allocation to leaf mass in maple and a slight enhancement of mean photosynthesis in aspen. Elevated [CO2] did not significantly affect aspen growth, and the observed stimulation of maple growth was significant only in mid-season. Correspondingly, simulated responses of whole-tree photosynthesis to elevated [CO2] were constrained by a decrease in photosynthetic capacity in maple, and were partially offset by reductions in specific leaf area and biomass allocation to foliage in aspen. There was a significant interaction between [CO2] and defoliation on only a few of the measured traits. Thus, the data do not support the hypothesis that atmospheric CO2 enrichment will substantially alter tree responses to folivory. However, our findings do provide further indication that regeneration-stage growth rates of certain temperate tree species may respond only moderately to a near doubling of atmospheric [CO2].


Prevalence of Borrelia burgdorferi in selected tick populations in Finland.
The purpose of the studies was to determine the prevalence of Borrelia burgdorferi sensu lato in selected populations of Ixodes ricinus in Finland and to secure strains of the spirochete for further characterization. 1,210 Ixodes ricinus ticks (399 females, 419 males and 392 nymphs) were collected during June to August 1992 by flagging from 8 sites in 3 regions. The frequency of B. burgdorferi infection was determined by isolation in BSK II medium. The species identity of most of the isolates was confirmed with the immunofluorescence method. 67 B. burgdorferi strains were isolated from 8 sites; the prevalence ranged from 2.8% to 7.9%. The overall isolation percentage for adult male ticks was 6.4% (7.5% for females, 5.3% for males); for nymphs, 3.8%. No statistically significant association of the prevalence was observed with either pasture or off-pasture habitats nor with specific geographic region/regions. Prevalence figures were roughly of the same magnitude in areas and parts of the country known to differ in their incidence of human borreliosis. An additional 294 ticks, mainly engorged females, were collected from places outside the main study sites. Of the 7 positive ticks 3 were engorged females, originating from a cow, a dog and a cat, respectively. The results in general demonstrate that tick populations in various parts of Finland quite commonly harbour B. burgdorferi.


A Cascade Random Forests Algorithm for Predicting Protein-Protein Interaction Sites.
Protein-protein interactions exist ubiquitously and play important roles in the life cycles of living cells. The interaction sites (residues) are essential to understanding the underlying mechanisms of protein-protein interactions. Previous research has demonstrated that the accurate identification of protein-protein interaction sites (PPIs) is helpful for developing new therapeutic drugs because many drugs will interact directly with those residues. Because of its significant potential in biological research and drug development, the prediction of PPIs has become an important topic in computational biology. However, a severe data imbalance exists in the PPIs prediction problem, where the number of the majority class samples (non-interacting residues) is far larger than that of the minority class samples (interacting residues). Thus, we developed a novel cascade random forests algorithm (CRF) to address the serious data imbalance that exists in the PPIs prediction problem. The proposed CRF resolves the negative effect of data imbalance by connecting multiple random forests in a cascade-like manner, each of which is trained with a balanced training subset that includes all minority samples and a subset of majority samples using an effective ensemble protocol. Based on the proposed CRF, we implemented a new sequence-based PPIs predictor, called CRF-PPI, which takes the combined features of position-specific scoring matrices, averaged cumulative hydropathy, and predicted relative solvent accessibility as model inputs. Benchmark experiments on both the cross validation and independent validation datasets demonstrated that the proposed CRF-PPI outperformed the state-of-the-art sequence-based PPIs predictors. The source code for CRF-PPI and the benchmark datasets are available online at http://csbio.njust.edu.cn/bioinf/CRF-PPI for free academic use.


Multifocal epithelioid hemangioendothelioma: case report of a clinical chamaeleon.
Epithelioid hemangioendothelioma is an extremely rare vascular bone tumor with a slow growth and poor prognosis. The term was designed to describe neoplasms that had an appearance in between hemangiomas and sarcomas. Various synonyms for epithelioid hemangioendothelioma are used clinically: low grade anaplastic angiosarcoma, cellular hemangioma, histiocytoid hemangioma and angioendothelioma. However, it represents 1% of all vascular neoplasms and is locally aggressive. We report the course of disease of a 47-year-old man who presented to our clinic with unspecific abdominal and back pain. Radiological findings revealed multiple lesions in the spine as well as liver and spleen involvement. Tumor histology of the bone and liver biopsies confirmed the diagnosis of epithelioid hemangioendothelioma. Although treatment was initiated with thalidomide, the patient developed multiple organ dysfunction syndrome (MODS) and succumbed to his disease. This case report may contribute to the data on clinical findings and natural history of this rare tumor.


Pro-cognitive action of CART is mediated via ERK in the hippocampus.
Although cocaine- and amphetamine-regulated transcript peptide (CART) is detected in several cortical and subcortical areas, its role in higher functions has been largely ignored. We examined the significance of CART in memory formation and tested if the downstream actions of CART involve N-methyl-d-aspartate (NMDA) activated extra-cellular signal-regulated kinase (ERK). Newly formed memory was evaluated using novel object recognition test consisting of familiarization (T1) and choice trials (T2). The choice trials were performed at two time points: 30-min (T230-min ) and 24-h (T224-h ) postacquisition. In choice trial (T230-min ), vehicle control rats explored the novel object for significantly longer duration than the familiar object indicating intact memory formation. However, CART-antibody, U0126 [ERK antagonist, both via intracerebroventricular (icv) or intrahippocampal (ih) route] or MK-801 (NMDA antagonist; intraperitoneal) treated rats spent less time exploring novel objects; CART peptide (icv or ih) was ineffective. During choice trial at T224-h , a significant decrease in novel object exploration time was noticed in vehicle control rats suggesting amnesia. However, treatment with CART, prior to familiarization trial (T1), promoted exploration of the novel object even at T224-h . Pretreatment with U0126 or MK-801 blocked pro-cognitive-like effect of CART suggesting involvement of NMDA-ERK pathway in CART's action. Animals subjected to the object familiarization trial showed a drastic increase in the CART-immunoreactivity in the cells of cornu ammonis 3 and polymorph layer of dentate gyrus, and fibers within ento- (ENT) and peri-rhinal (PRH) cortices. Western blot analysis revealed that CART treatment significantly up-regulated the expression of phospo-ERK1/2 in hippocampus, ENT and PRH. This effect was attenuated following pretreatment with U0126 or MK-801, suggesting the activation of ERK signaling cascade through NMDA receptors. Thus, CART system seems to play an important role in recognition memory and that these effects may be mediated by NMDA receptors-ERK signaling in the ENT/PRH-hippocampal circuit. © 2016 Wiley Periodicals, Inc.


The effects of age on the structure and porphyrin synthesis of the harderian gland of the female golden hamster.
The effects of age on structure and porphyrin synthesis were examined in the Harderian gland of the female golden hamster. An age range of 2-24 months was examined. Porphyrin enzyme activity reached a peak at 6 months and then declined; the porphyrin content of the gland (as determined both by biochemical assay and by the number of visible porphyrin accretions) also declined from 6 months. Mast cells, found in large numbers in the actively synthesising female gland, declined with age. Conversely, tubule epithelial cells with large lipid vacuoles (Type II cells--characteristic of the non-synthesising male gland) increased in frequency. There was considerable evidence of degenerative changes in gland structure with age. These included thinning of the tubule walls, invasion of the tubule lumen by neutrophils and the appearance of porphyrin stores within the interstitium of the gland. The latter were either large accretions surrounded by foreign body giant cells, or smaller deposits within individual free macrophages. Changes may be the result of ageing itself, of hormone insufficiency in post-reproductive senescence or inflammatory processes.


Intrafraction bladder motion in radiation therapy estimated from pretreatment and posttreatment volumetric imaging.
The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatment and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patient's bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between pretreatment and posttreatment imaging. Asymmetric expansion of CTV to PTV should be considered. Care is required in using image-guided radiation therapy protocols that reduce CTV to PTV margins based only on daily pretreatment soft tissue position.


Genetic Differentiation of Opisthorchis-Like Eggs in Northern Thailand Using Stool Specimens Under National Strategic Plan to Control Liver Fluke Infection and Cholangiocarcinoma.
Liver fluke infection caused by Opisthorchis viverrini is recognized as a potential risk factor for cholangiocarcinoma (CCA). The National Strategic Plan to Control Liver Fluke Infection and Cholangiocarcinoma has implemented microscopic-based stool examination screening. However, eggs of O. viverrini and minute intestinal flukes (MIFs) are nearly morphologically similar and could result in inaccurate O. viverrini diagnosis. Stool specimens were collected from eight districts of Chiang Mai Province in northern Thailand. Opisthorchis-like eggs were identified with the Kato-Katz technique and differentiated for O. viverrini and MIFs using molecular study by PCR and PCR-restriction fragment length polymorphism targeting the internal transcribed spacer 2 (ITS2) gene. Prevalence of Opisthorchis-like eggs was 5.9% from a total of 9,570 specimens. From PCR assays, all liver flukes were O. viverrini and all MIFs were Haplorchis taichui. The distribution of species was H. taichui (38.2%), O. viverrini (10.5%), coinfection of H. taichui and O. viverrini (37.2%), and 14.1% were negative from PCR. Totally, H. taichui was found in 75.4% of infections from Opisthorchis-like specimens. ITS2 nucleotide sequencing analysis showed a single variant of O. viverrini with no variation and two variants of H. taichui. This study first revealed the genetic background of Opisthorchis-like eggs in northern Thailand. Minute intestinal flukes are occasionally misdiagnosed as O. viverrini leading to misinterpretation and overestimation of the burden of O. viverrini infection. Molecular diagnosis such as PCR could effectively discriminate species of Opisthorchis-like eggs and help shape the robustness of epidemiological data to control liver fluke infection and raise awareness of other risk factors for CCA.


PRODAN dual emission feature to monitor BHDC interfacial properties changes with the external organic solvent composition.
We have investigated the water/benzyl-n-hexadecyldimethylammonium chloride (BHDC)/n-heptane:benzene reverse micelles (RMs) interfaces properties using 6-propionyl-2-(N,N-dimethyl)aminonaphthalene, PRODAN, as molecular probe. We have used absorption and emission (steady-state and time-resolved) spectroscopy of PRODAN to monitor the changes in the RMs interface functionalities upon changing the external organic solvent blend. We demonstrate that PRODAN is a useful probe to investigate how the external solvent composition affects the micelle interface properties. Our results show that changes in the organic solvent composition in water/BHDC/n-heptane:benzene RMs have a dramatic effect on the photophysics of PRODAN. Thus, increasing the aliphatic solvent content over the aromatic one produces PRODAN partition and PRODAN intramolecular electron transfer (ICT) processes. Additionally, the water presence in these RMs makes the PRODAN ICT process favored with the consequent decreases in the LE emission intensity and a better definition of the charge transfer (CT) band. All this evidence suggests that the benzene molecules are expelled out of the interface, and the water-BHDC interactions are stronger with more presence of water molecules in the polar part of the interface. Thus, we demonstrate that a simple change in the composition of the external phase promotes remarkable changes in the RMs interface. Finally, the results obtained with PRODAN together with those reported in a previous work in our lab reveal that the external phase is important when trying to control the properties of RMs interface. It should be noted that the external phase itself, besides the surfactant and the polar solvent sequestrated, is a very important control variable that can play a key role if we consider smart application of these RMs systems.


Endocytic accessory factors and regulation of clathrin-mediated endocytosis.
Up to 60 different proteins are recruited to the site of clathrin-mediated endocytosis in an ordered sequence. These accessory proteins have roles during all the different stages of clathrin-mediated endocytosis. First, they participate in the initiation of the endocytic event, thereby determining when and where endocytic vesicles are made; later they are involved in the maturation of the clathrin coat, recruitment of specific cargo molecules, bending of the membrane, and finally in scission and uncoating of the nascent vesicle. In addition, many of the accessory components are involved in regulating and coupling the actin cytoskeleton to the endocytic membrane. We will discuss the different accessory components and their various roles. Most of the data comes from studies performed with cultured mammalian cells or yeast cells. The process of endocytosis is well conserved between these different organisms, but there are also many interesting differences that may shed light on the mechanistic principles of endocytosis.


[Biosynthesis of purine nucleotides in the rat muscle after castration].
The paper describes the effects of castration on formate-14C incorporation into the acid-soluble purines and into the nucleic acids of skeletal muscles (ELD and G) and perineal muscle (LAM). 20% homogenates were prepared in 1 M HC10(4), centrifuged and the nucleic acid were extracted from the precipitate with 0.7 N PCA (15 min at 90 degrees C). The acid-soluble purines were precipitated with 1 M AgNO3 from the supernatant of the centrifuged homogenate, then extracted with 1 M HC1 and separated by ion exchange chromatography with a scalar gradient of HC1. In the LAM a significant decrease in the specific activity of the purine bases (A, -56%, P less than 0.01; G, -47%, P less than 0.05) and of the nucleic acid (-47%, P less than 0.01) was observed after castration, while no difference was observed in skeletal muscles.


Blood culture-negative endocarditis: Improving the diagnostic yield using new diagnostic tools.
Blood culture-negative endocarditis (BCNE) may represent up to 70% of all endocarditis cases, depending on series. From 2001 to 2009, we implemented in our laboratory a multimodal diagnostic strategy for BCNE that included systematized testing of blood, and when available, valvular biopsy specimens using serological, broad range molecular, and histopathological assays. A causative microorganism was identified in 62.7% of patients.In this study from January 2010 to December 2015, in an effort to increase the number of identified causative microorganisms, we prospectively added to our diagnostic protocol specific real-time (RT) polymerase chain reaction (PCR) assays targeting various endocarditis agents, and applied them to all patients with BCNE admitted to the 4 public hospitals in Marseille, France.A total of 283 patients with BCNE were included in the study. Of these, 177 were classified as having definite endocarditis. Using our new multimodal diagnostic strategy, we identified an etiology in 138 patients (78.0% of cases). Of these, 3 were not infective (2.2%) and 1 was diagnosed as having Mycobacterium bovis BCG endocarditis. By adding specific PCR assays from blood and valvular biopsies, which exhibited a significantly greater sensitivity (P < 10) than other methods, causative agents, mostly enterococci, streptococci, and zoonotic microorganisms, were identified in an additional 27 patients (14 from valves only, 11 from blood only, and 2 from both). Finally, in another 107 patients, a pathogen was detected using serology in 37, valve culture in 8, broad spectrum PCR from valvular biopsies and blood in 19 and 2, respectively, immunohistochemistry from valves in 3, and a combination of several assays in 38.By adding specific RT-PCR assays to our systematic PCR testing of patients with BCNE, we increased the diagnostic efficiency by 24.3%, mostly by detecting enterococci and streptococci that had not been detected by other diagnostic methods, but also agents requiring specific management such as Mycoplasma hominis and Tropheryma whipplei.


ALK and ROS1 testing on lung cancer cytologic samples: Perspectives.
Cytologic sampling is the mainstay of diagnosing advanced lung cancer. Moreover, to select patients for personalized first-line or second-line treatment, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements are tested on cytologic preparations. Commercially available fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) assays have primarily been used for the identification of cells harboring ALK or ROS1 gene fusions on histologic rather than cytologic preparations. However, it is now recognized that FISH and ICC also can be applied on cytologic samples provided the cytopathologist is aware that FISH and ICC results are not always concordant and that the performance of ICC largely depends on antibody clones, signal detection systems, and scoring systems. Notably, the routine clinical use of FISH and ICC may be replaced by emerging next-generation sequencing and digital, color-coded barcode technologies, which have the advantage of simultaneously evaluating ALK, ROS1, and EGFR alterations in a single analysis. Although their use in clinical cytologic practice remains to be fully established, it is conceivable that this technology will replace both FISH and ICC analyses in future diagnostic algorithms. Here, the authors review studies devoted to testing ALK and ROS1 on cytology specimens in an attempt to provide an update for the cytopathologist regarding current and evolving practice. Cancer Cytopathol 2017;125:817-30. © 2017 American Cancer Society.


Novel potential reservoirs for Borrelia sp. and the agent of human granulocytic ehrlichiosis in Colorado.
Previous work demonstrated that Ixodes spinipalpis ticks maintained an enzootic cycle of Borrelia bissettii and the agent of human granulocytic ehrlichiosis (aoHGE) within woodrats (Neotoma mexicana) and deer mice (Peromyscus maniculatus) in northern Colorado (USA). Because I. spinipalpis is the only known vector of B. bissettii and aoHGE in Colorado, this study was designed to determine the reservoir status of other hosts of I. spinipalpis in five distinct ecological zones along the front range and foothills of Colorado. One hundred and twelve rodents of nine species were examined and 11 (10%) were polymerase chain reaction (PCR) positive for aoHGE; 37 (33%) were culture positive for B. bissettii, and five (4%) were coinfected with both organisms based on PCR and culture. Of these, three chipmunk species (Tamias minimus, T. quadrivittatus, and T. umbrinus) were culture positive for B. bissettii, with a single T. minimus coinfected with B. bissettii and aoHGE. In addition, one golden-mantled ground squirrel (Spermophilus lateralis) was positive for both B. bissettii and aoHGE. This is the first report of a golden-mantled ground squirrel harboring either B. bissettii or aoHGE and the initial observation that chipmunks may be a reservoir for B. bissettii in Colorado.


Association of lymphocytic colitis and lactase deficiency in pediatric population.
Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone.


Is it possible and worth keeping track of deaths within general practice? Results of a 15 year observational study.
To assess the value of maintaining a death register in a general practice with particular reference to monitoring quality of care. Observational study. Inner London general practice. The practice maintained a manual death register, retained medical records of all deceased patients, and requested information on cause of death from health authorities and coroners for 15 years. Number and causes of deaths; 3 yearly age standardised death rates; proportion of deaths formally notified to the practice; place of death; source of cause of death information. During the study period 578 patients died. Practice age standardised death rates fell significantly from 35.59 to 27.12/1000. 498 (86.2%) deaths were formally notified to the practice, 392 within 7 days of death. Of 143 deaths reported to the coroner, only 45 coroners' reports were received. 360 (64.1%) died in hospital, 139 (24.8%) at home, and 38 (6.8%) in a hospice. Death certificate cause of death information was obtained from patients' records in 33.6% (n=194) of cases and from health authority sources for 50% (n=289). The pattern of ascertained causes of deaths was similar to the national pattern. A death register can examine trends in practice deaths by age and place of death and comparisons undertaken with nationally published mortality data. An accurate picture of cause of death cannot be generated from routine data flows alone. There is delay in informing GPs of patient deaths. Meaningful and timely monitoring of deaths cannot be undertaken by individual practices. National Statistics should provide routine analysis of GP death certificate information.


Encapsulation of cell-adhesive RGD peptides into a polymeric physical hydrogel to prevent postoperative tissue adhesion.
Peptides containing the sequence of arginine-glycine-aspartate (RGD), a famous adhesion moiety, can specifically conjugate integrins in cell membranes, and are usually applied to enhance cell adhesion after linking to solid substrates in tissue engineering or to nanoparticles in targeting delivery. This paper reveals, however, that free RGD peptides can assist in preventing tissue adhesion by blocking focal adhesion between cells and surfaces of barrier devices. In order to avoid a rapid peptide loss after straightforward injection of a peptide solution, we employed a thermosensitive injectable hydrogel composed of a biodegradable block copolymer poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) to encapsulate peptides cyclo(-RGDfK-). A sustainable release for one week was achieved in vitro. The rabbit model of sidewall defect and bowel abrasion was selected to examine the in vivo anti-adhesion efficacy. It reveals a significant reduction of postoperative peritoneal adhesion in the group of RGD-loaded PCLA-PEG-PCLA hydrogels. We interpret this excellent efficacy by the combination of two effects: first, our hydrogel affords a physical barrier to prevent adhesion between injured abdominal wall and cecum; second, the RGD molecules as integrin blockers released from the hydrogel assist the anti-adhesion.


Effect of filtration flux on the development and operation of a dynamic membrane for anaerobic wastewater treatment.
Dynamic membrane represents a cost effective alternative to conventional membranes by employing fouling as a means of solid-liquid separation. This study evaluated the effects of initial flux on both development rate of dynamic membrane and bioreactor performance during two consecutive experiments. The dynamic membrane was developed over a 200 μm mesh and the reactor was operated under anaerobic conditions. It was found that the effect of an initial higher applied flux on dynamic membrane development was more pronounced than mixed liquor suspended solid concentration inside the bioreactor. The development of the dynamic membrane was therefore positively associated with the applied flux. The rapid development of the dynamic membrane during the second experimental run at high initial fluxes and lower MLSS concentrations also affected the performance of the bioreactor in terms of more efficient COD removal and biogas production. A major shortcoming of applying higher initial applied flux was the formation of a denser and robust dynamic membrane layer that was resistant to applied hydraulic shear to control desired permeability and thus represented an obstacle in maintaining a long term operation with sustainable flux at lower transmembrane pressure (TMP).


An imageomics and multi-network based deep learning model for risk assessment of liver transplantation for hepatocellular cancer.
Liver transplantation (LT) is an effective treatment for hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Patients with small HCC (<5 cm) are given priority over others for transplantation due to clinical allocation policies based on tumor size. Attempting to shift from the prevalent paradigm that successful transplantation and longer disease-free survival can only be achieved in patients with small HCC to expanding the transplantation option to patients with HCC of the highest tumor burden (>5 cm), we developed a convergent artificial intelligence (AI) model that combines transient clinical data with quantitative histologic and radiomic features for more objective risk assessment of liver transplantation for HCC patients. Patients who received a LT for HCC between 2008-2019 were eligible for inclusion in the analysis. All patients with post-LT recurrence were included, and those without recurrence were randomly selected for inclusion in the deep learning model. Pre- and post-transplant magnetic resonance imaging (MRI) scans and reports were compressed using CapsNet networks and natural language processing, respectively, as input for a multiple feature radial basis function network. We applied a histological image analysis algorithm to detect pathologic areas of interest from explant tissue of patients who recurred. The multilayer perceptron was designed as a feed-forward, supervised neural network topology, with the final assessment of recurrence risk. We used area under the curve (AUC) and F-1 score to assess the predictability of different network combinations. A total of 109 patients were included (87 in the training group, 22 in the testing group), of which 20 were positive for cancer recurrence. Seven models (AUC; F-1 score) were generated, including clinical features only (0.55; 0.52), magnetic resonance imaging (MRI) only (0.64; 0.61), pathological images only (0.64; 0.61), MRI plus pathology (0.68; 0.65), MRI plus clinical (0.78, 0.75), pathology plus clinical (0.77; 0.73), and a combination of clinical, MRI, and pathology features (0.87; 0.84). The final combined model showed 80 % recall and 89 % precision. The total accuracy of the implemented model was 82 %. We validated that the deep learning model combining clinical features and multi-scale histopathologic and radiomic image features can be used to discover risk factors for recurrence beyond tumor size and biomarker analysis. Such a predictive, convergent AI model has the potential to alter the LT allocation system for HCC patients and expand the transplantation treatment option to patients with HCC of the highest tumor burden.


Immunoserological changes in the cerebro-spinal fluid and serum in systemic lupus erythematosus patients with demyelinating syndrome and multiple sclerosis.
The aim of the present study was to investigate the role of antinuclear and antiphospholipid antibodies in the pathogenesis of systemic lupus erythematosus (SLE) with demyelinating syndrome and several forms of multiple sclerosis (MS). Paired samples of serum and cerebrospinal fluid (CSF) were investigated using laser nephalometric and enzyme linked immunosorbant assay (ELISA) methods, and the parameters of intrathecal synthesis were calculated. Elevation of the concentrations of antiribosomal P protein antibodies in the CSF and serum, and intrathecal synthesis anticardiolipin (aCL) antibodies were characteristic in all patient groups. The immunoserological changes were more pronounced in the SLE patients. A similar pathogenetic role of antiphospholipid antibodies in central nervous system (CNS) damage in SLE patients with demyelinating syndrome and of MS patients can be assumed.


Complex distribution patterns, ecology and coexistence of ploidy levels of Allium oleraceum (Alliaceae) in the Czech Republic.
Despite extensive study of polyploidy, its origin, and ecogeographical differences between polyploids and their diploid progenitors, few studies have addressed ploidy-level structure and patterns of ecogeographical differentiation at various spatial scales using detailed sampling procedures. The pattern of coexistence of polyploids in the geophyte Allium oleraceum at the landscape and locality scale and their ecology were studied. Flow cytometry and root-tip squashes were used to identify the ploidy level of 4347 plants from 325 populations sampled from the Czech Republic using a stratified random sampling procedure. Ecological differentiation among ploidy levels was tested by comparing sets of environmental variables recorded at each locality. Across the entire sampling area, pentaploids (2n = 5x = 40) predominated, while hexaploids (2n = 6x = 48) and tetraploids (2n = 4x = 32) were less frequent. The distribution of tetra- and hexaploids was partially sympatric (in the eastern part) to parapatric (in the western part of the Czech Republic) whereas pentaploids were sympatric with other cytotypes. Plants of different ploidy levels were found to be ecologically differentiated and the ruderal character of cytotypes increased in the direction 4x --> 5x --> 6x with the largest realized niche differences between tetra- and hexaploids. Most populations contained only one ploidy level (77 %), 22 % had two (all possible combinations) and 1 % were composed of three ploidy levels. The majority of 4x + 5x and 5x + 6x mixed populations occurred in sympatry with uniform populations of the participating cytotypes in sites with ecologically heterogeneous or marginal environment, suggesting secondary contact between cytotypes. Some mixed 4x + 6x populations dominated by tetraploids being sympatric and intermixed with uniform 4x populations might represent primary zones of cytotype contact. Almost no mixed accessions were observed on the fine spatial scale in mixed populations. The results provide evidence for adaptive differences among ploidy levels, which may contribute to their complex distribution pattern. The prevalence of asexual reproduction, limited dispersal and equilibrium-disrupting processes may support local coexistence of cytotypes.


Alarming Increasing Trends in Hospitalizations and Mortality With Heyde's Syndrome: A Nationwide Inpatient Perspective (2007 to 2014).
We studied the trends and outcomes of patients with intestinal angiodysplasia-associated gastrointestinal bleeding (Heyde's syndrome [HS]) with aortic stenosis (AS) who underwent surgical aortic valve replacement (SAVR) versus transcatheter aortic valve implantation (TAVI). The National Inpatient Sample (2007 to 2014) and International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HS hospitalizations, pertinent co-morbidities, and outcomes of SAVR versus TAVI from 2011 to 2014. The incidence of HS with AS was 3.1%. The trends in hospitalizations and all-cause inpatient mortality showed relative surges of 29.16% (from 48 to 62 per 100,000) and 22.7% (from 3.7 to 4.54 per 100,000) from 2007 to 2014. HS patients were older (mean age ∼80 vs 77 years) females (54.3% vs 52.2%) compared with AS without HS. The all-cause mortality (6.9% vs 4.1%), length of stay (LOS) (∼7.0 vs 5.8 days), and hospitalization charges ($58,519.31 vs $57,598.67) were higher in HS (p<0.001). No differences were reported in all-cause mortality and hospital charges in HS patients who underwent either SAVR or TAVI. However, the TAVI cohort showed lower rates of stroke (1.7% vs 10.0%) and blood transfusion (1.7% vs 11.7%), a shorter LOS (18.3 vs 23.9 days; p<0.001), and more routine discharges (21.7% vs 14.8%, p = 0.01). An older age, male gender, Asian race, congestive heart failure, coagulopathy, fluid and/or electrolytes disorders, chronic pulmonary disease, and renal failure raised the odds of mortality in HS patients. In conclusion, we observed increasing rates of hospitalizations with HS and higher inpatient mortality from 2007 to 2014. The HS patients who underwent TAVI had fewer complications without any difference in the all-cause mortality compared with SAVR.


Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as 'sponges' of Gd3+ ions.
MR-labeling of cells may be carried out by adding a Gd-based contrast agent to the incubation media. The amount of gadolinium internalized in HTC and C6 cells upon incubation with Gd-DTPA-BMA is circa one order of magnitude higher than those found with Gd-DTPA, Gd-DOTA and Gd-HPDO3A, respectively. The comparison of relaxometric and mass spectrometry determinations allows us to establish that only a minor fraction of intact Gd-DTPA-BMA is internalized into the cells. Moreover the binding/uptake behavior shown by Gd-DTPA-BMA resembles that found when GdCl(3) is added to the incubation medium. We suggest that the lower stability of Gd-DTPA-BMA is responsible for a shift in the dissociation equilibrium that results in the net transfer of Gd(3+) ions on the cell membrane followed by a slower internalization process. The transmetallation process is mediated by components of the incubation media, among which a dominant role is represented by phosphate anions. The uptake of Gd(3+) ions is clearly reflected in the drastic decrease of cell viability observed for cells labeled with Gd-DTPA-BMA.


Crystal and Supramolecular Structure of Bacterial Cellulose Hydrolyzed by Cellobiohydrolase from Scytalidium Candidum 3C: A Basis for Development of Biodegradable Wound Dressings.
The crystal and supramolecular structure of the bacterial cellulose (BC) has been studied at different stages of cellobiohydrolase hydrolysis using various physical and microscopic methods. Enzymatic hydrolysis significantly affected the crystal and supramolecular structure of native BC, in which the 3D polymer network consisted of nanoribbons with a thickness T ≈ 8 nm and a width W ≈ 50 nm, and with a developed specific surface SBET ≈ 260 m2·g-1. Biodegradation for 24 h led to a ten percent decrease in the mean crystal size Dhkl of BC, to two-fold increase in the sizes of nanoribbons, and in the specific surface area SBET up to ≈ 100 m2·g-1. Atomic force and scanning electron microscopy images showed BC microstructure "loosening"after enzymatic treatment, as well as the formation and accumulation of submicron particles in the cells of the 3D polymer network. Experiments in vitro and in vivo did not reveal cytotoxic effect by the enzyme addition to BC dressings and showed a generally positive influence on the treatment of extensive III-degree burns, significantly accelerating wound healing in rats. Thus, in our opinion, the results obtained can serve as a basis for further development of effective biodegradable dressings for wound healing.


Can radiology replace endoscopy in IBD?
Inflammatory bowel disease diagnostic and management algorithms continue to rapidly evolve. This is partly driven by advanced radiologic techniques that provide objective, non-invasive evaluations. The realms of information provided by radiology and endoscopy continue to be intertwined. This has led to the question of whether radiologic applications will continue to expand, and eventually replace endoscopy in inflammatory bowel disease assessments. The likely outcome, however, will not be replacement, but rather imaging tools that complement endoscopic evaluations to provide global disease damage and activity scores.


Influence of cell isolation and incubation procedures on Ca2+ dependence of glucose transport in isolated cardiac myocytes.
Insulin stimulates hexose transport in isolated myocytes of adult rats but data are conflicting regarding the Ca2+-dependence of this effect, demonstrated previously in intact heart muscle. 3-O-methyl-D-glucose and 2-deoxy-D-glucose transport was compared in cells prepared and incubated by different published procedures. Ca2+-dependence of hexose transport stimulation by insulin was found only with incubation in a modified Joklik tissue culture medium buff red with bicarbonate at pH 7.4. At pH 7.0 or when bicarbonate was replaced by N-2-hydroxyethylpiperazine-N'-2 ethane sulfonic acid (HEPES) stimulation by insulin was not Ca2+-dependent, nor was there a Ca2+-dependent increment in insulin effect in physiological saline media regardless of pH or buffer (HEPES, 3-[N-morpholino] propanesulfonic acid (MOPS) or bicarbonate). The ATP content of cells incubated in HEPES or MOPS media was reduced. Ca2+-dependence seems to require the presence of bicarbonate and another factor(s) in tissue culture medium. The response is also influenced by the isolation procedure and may be related in part to preservation of an intact glycocalix. Thus, details in cell isolation and incubation procedures may strongly influence the behaviour of the cells. Isolated cardiac myocytes are acceptable as a valid model only if it can be demonstrated in each specific case that the characteristics present in intact tissue are maintained unaltered in the isolated cells.