Injuries caused by water tubing.
Water tubing (the pulling of an inner tube behind a power boat) is growing in popularity and unfortunately is becoming an increasing source of pediatric trauma. This is related to the lack of control of either the driver or the rider in directing the inner tube away from objects in the water or along the shore. Because of the severe trauma from this increasingly popular sport, we thought it appropriate to review our experience at a major pediatric trauma center to draw attention to this increasing cause of injury in children and to develop guidelines to reduce such injuries. A retrospective review of children admitted over a 10-year period revealed eight children who required admission to hospital for injuries sustained in water tubing. Five patients sustained fractures, one a splenic contusion, and two atlantoaxial rotatory subluxation. A set of safety guidelines for water tubing has been developed in an attempt to minimize the dangers to children who wish to pursue this sport.


Folding mechanism of a polymer chain with short-range attractions.
We investigate the crystallization of a single, flexible homopolymer chain using transition path sampling. The chain consists of N identical spherical monomers evolved according to Langevin dynamics. While neighboring monomers are coupled via harmonic springs, the non-neighboring monomers interact via a hard core and a short-ranged attractive potential. For a sufficiently small interaction range λ, the system undergoes a first-order freezing transition from an expanded, disordered phase to a compact crystalline state. Using a new shooting move tailored to polymers combined with a committor analysis, we study the transition state ensemble of an N = 128 chain and search for possible reaction coordinates based on likelihood maximization. We find that typical transition states consist of a crystalline nucleus with one or more chain fragments attached to it. Furthermore, we show that the number of particles in the crystalline core is not well suited as a reaction coordinate. We then present an improved reaction coordinate, which includes information from the potential energy and the overall crystallinity of the polymer.


Critical aspects of educating clinical management and clinical reasoning in primary teeth pulpotomy: A qualitative study based on the perspectives of experts and novices.
In dental education, students must learn to integrate and coordinate complex knowledge, skills and attitudes and to transfer this learning to clinical practice. One major issue of concern in education in general and dental education, in particular, is to fill the gap between knowledge and practice. The purpose of this study was to explore the problems that dental students have in transferring knowledge from the classroom to the real clinical setting. More specifically, we investigated the factors that complicate clinical management and clinical reasoning for these novices, including their common errors, in order to design an educational simulation programme in primary teeth pulpotomy. To this end, we conducted 16 semi-structured interviews with experts and novices, performing a thematic analysis of the data obtained. All interviews were audio recorded and transcribed verbatim. For each major skill-clinical management and clinical reasoning-we identified complicating factors and common errors that related to the child (the patient), parents and dental student (the three main themes). For each theme, we identified further sub-themes. The data obtained provided valuable insights into the factors that affect dental students' performance on clinical management and clinical reasoning in primary teeth pulpotomy.


An Update on Health-Related Quality of Life and Patient-Reported Outcomes in Hidradenitis Suppurativa.
Hidradenitis suppurativa is a common inflammatory skin condition which causes recurrent abscesses, sinuses and scarring in the axillae, groin and inframammary areas. As well as causing significant physical distress due to pain and discharge, the condition impacts psychological well-being with markedly impaired quality of life. Patients suffer pain, embarrassment and psychological distress with impairment of their work and intimate relationships marking it as one of the most distressing dermatological conditions. Numerous studies have documented markers of psychological distress encompassing the physical effects such as pain and itch, affects on mood and impaired function.


Primary endothelial dysfunction: atherosclerosis.
The endothelium synthesizes and releases several vasodilating factors, including nitric oxide, endothelium-derived hyperpolarizing factor, and prostacyclin. Under certain conditions, it also liberates vasocontracting factors. Thus, the endothelium plays an important role in regulating vascular homeostasis. Several intracellular mechanisms are involved in the synthesis of nitric oxide, including receptor-coupled G proteins, the availability of L-arginine, cofactors for endothelial nitric oxide synthase and the expression of the enzyme. Endothelial dysfunction by aging, menopause and hypercholesterolemia is involved in the development of atherosclerotic vascular lesions, and predisposes the blood vessel to several vascular disorders, such as vasospasm and thrombosis. Multiple mechanisms are apparently involved in the pathogenesis of the endothelial dysfunction in atherosclerosis. The reduced production of nitric oxide by the endothelium is caused by abnormalities in endothelial signal transduction, availability of L-arginine, cofactors for endothelial nitric oxide synthase and expression of the enzyme. Other mechanisms may also be involved in the impaired endothelium-dependent relaxations in atherosclerosis, including increased destruction of nitric oxide by superoxide anion, altered responsiveness of vascular smooth muscle, and concomitant release of vasocontracting factors. In addition to the treatment of the underlying risk factors, several pharmacological agents can improve endothelial dysfunction in atherosclerosis. Thus, the endothelium is a novel therapeutic target for the treatment of atherosclerotic cardiovascular disease.


Intramucosal nevus of buccal mucosa in a male child.
Nevus (mole or birthmark) is a benign tumour of skin and mucosa characterised by the presence of melanin-producing, neuroectodermally derived cells, which can be light to dark brown, reddish brown, blue or flesh coloured. It varies in shape from oval to round. Oral melanotic nevi are uncommon oral lesions causing focal pigmentation. They were found only in 0.1% of population in a large survey. Nevi can be acquired over time or congenital. Acquired nevi are considered benign neoplasms whereas congenital nevi are hamartomas. They are located usually on the palate but less commonly on buccal mucosa, gingiva and lips. This article presents a case report of an intramucosal nevus of buccal mucosa in a 5-year-old boy with its surgical removal.


Less is more: extreme genome complexity reduction with ddRAD using Ion Torrent semiconductor technology.
Massively parallel sequencing a small proportion of the whole genome at high coverage enables answering a wide range of questions from molecular evolution and evolutionary biology to animal and plant breeding and forensics. In this study, we describe the development of restriction-site associated DNA (RAD) sequencing approach for Ion Torrent PGM platform. Our protocol results in extreme genome complexity reduction using two rare-cutting restriction enzymes and strict size selection of the library allowing sequencing of a relatively small number of genomic fragments with high sequencing depth. We applied this approach to a common freshwater fish species, the Eurasian perch (Perca fluviatilis L.), and generated over 2.2 MB of novel sequence data consisting of ~17,000 contigs, identified 1259 single nucleotide polymorphisms (SNPs). We also estimated genetic differentiation between the DNA pools from freshwater (Lake Peipus) and brackish water (the Baltic Sea) populations and identified SNPs with the strongest signal of differentiation that could be used for robust individual assignment in the future. This work represents an important step towards developing genomic resources and genetic tools for the Eurasian perch. We expect that our ddRAD sequencing protocol for semiconductor sequencing technology will be useful alternative for currently available RAD protocols.


Review of airborne emissions from agricultural fumigants: design and uncertainty considerations for the use of the integrated horizontal flux method.
Ground-level area sources, such as those associated with the use of agricultural fumigants, waste disposal sites, wastewater lagoons, and other applications, present a challenge in terms of characterizing atmospheric flux as a function of time. Studies are costly in terms of field activities and laboratory analysis. The optimization of field study design, therefore, is essential to conduct cost-effective research. The collection of on-field profile data for airborne concentration, wind speed, and wind direction can be used in conjunction with the integrated horizontal flux (IHF) method to empirically compute complex source terms as a function of time. This paper focuses on complicating factors and field study design issues for the use of the IHF method. Insights and examples are drawn from five field research studies. The methods and results of characterizing the uncertainty and method precision in the emission fitting for the IHF method also are presented.


Legal aspects of visual field assessment.
Visual field testing can fail to satisfy the standard of care if the optometrist does not test the patient's visual field when it is necessary, and if, even when testing is performed, it is of insufficient sensitivity. In general, the duty to test the visual field arises when examining symptomatic patients and when a suspicious finding is encountered, but "routine" eye health assessments should include a screening visual field test. In some cases the doctrine of informed consent will require the optometrist to inform the patient that testing of the visual field at threshold should be performed. Documentation of both test results and patient communications should be retained in the record.


Certolizumab pegol.
Certolizumab pegol (Cimzia(®)) is currently the only PEGylated anti-TNFα biologic approved for the treatment of rheumatoid arthritis and Crohn disease. The product, developed by UCB, is a humanized antigen-binding fragment (Fab') of a monoclonal antibody that has been conjugated to polyethylene glycol. Certolizumab pegol was approved as a treatment for rheumatoid arthritis in the EU, US and Canada in 2009, and as a treatment for Crohn disease in Switzerland in 2007 and the US in 2008. Certolizumab pegol is entering into an increasingly competitive marketplace, especially in rheumatoid arthritis, but clinical data demonstrate benefits across a range of clinical, radiographic and patient reported outcomes.


L-isoleucine and L-leucine: tumor promoters of bladder cancer in rats.
A 4-week assay for screening tumor promoters of bladder cancer has been developed in which increased agglutinability of isolated rat bladder cells with concanavalin A is used as an indicator. On the basis of this assay system, L-isoleucine and L-leucine were suspected of being possible tumor promoters. Results of 40- to 60-week carcinogenesis experiments in which N-butyl-N-(4-hydroxybutyl)nitrosamine was used as an initiator demonstrate that L-isoleucine and L-leucine promote bladder cancer in rats. This finding may be relevant to the high incidence of human bladder cancer in Western countries, where the diet is rich in protein.


Do street-level scene perceptions affect housing prices in Chinese megacities? An analysis using open access datasets and deep learning.
Many studies have explored the relationship between housing prices and environmental characteristics using the hedonic price model (HPM). However, few studies have deeply examined the impact of scene perception near residential units on housing prices. This article used house purchasing records from FANG.com and open access geolocation data (including massive street view pictures, point of interest (POI) data and road network data) and proposed a framework named "open-access-dataset-based hedonic price modeling (OADB-HPM)" for comprehensive analysis in Beijing and Shanghai, China. A state-of-the-art deep learning framework and massive Baidu street view panoramas were employed to visualize and quantify three major scene perception characteristics (greenery, sky and building view indexes, abbreviated GVI, SVI and BVI, respectively) at the street level. Then, the newly introduced scene perception characteristics were combined with other traditional characteristics in the HPM to calculate marginal prices, and the results for Beijing and Shanghai were explored and compared. The empirical results showed that the greenery and sky perceptual elements at the property level can significantly increase the housing price in Beijing (RMB 39,377 and 6011, respectively) and Shanghai (RMB 21,689 and 2763, respectively), indicating an objectively higher willingness by buyers to pay for houses that provide the ability to perceive natural elements in the surrounding environment. This study developed quantification tools to help decision makers and planners understand and analyze the interaction between residents and urban scene components.


Differential expression of claudin tight junction proteins in the human cortical nephron.
In renal tubules, paracellular permeability is tightly controlled to facilitate solute absorption and urinary concentration and is regulated by tight junctions, which incorporate claudin proteins. There is very limited information confirming the localization of these proteins in the human renal cortex. Most data is inferred from mouse, bovine and rabbit studies and differences exist between mouse and other species. A survey of claudin staining was performed on human kidney cortex embedded in glycolmethacrylate resin to enhance tissue morphology and facilitate the cutting of 2 microm serial sections. Claudin-2, -10 and -11 antibodies labelled renal tubular epithelial cells, correlating with Lotus tetragonolobus and N-cadherin positive proximal tubules. Claudin-3, -10, -11 and -16 antibodies strongly stained a population of tubules that were positive for Tamm Horsfall protein on adjacent sections, confirming expression in the thick ascending limb of the Loop of Henle. Claudin-3, -4 and -8 antibodies reacted with tubules that correlated with the distal nephron markers, E-cadherin, epithelial membrane antigen and Dolichos biflorus and claudin-3, -4, -7 and -8 with the distal tubule marker, calbindin, and the collecting duct marker, aquaporin-2. Claudin-14 was localized in distal convoluted tubules, correlating positively with calbindin but negatively with aquaporin-2, whereas claudin-1 staining was identified in the parietal epithelium of Bowman's capsule, distal convoluted tubule and collecting duct. Cellular and tight junction localization of claudin staining in renal tubules was heterogeneous and is discussed. Complex variation in the expression of human claudins likely determines paracellular permeability in the kidney. Altered claudin expression may influence pathologies involving abnormalities of absorption.


Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells.
Radiotherapy is a curative treatment option in prostate cancer. Nevertheless, patients with high-risk prostate cancer are prone to relapse. Identification of the predictive biomarkers and molecular mechanisms of radioresistance bears promise to improve cancer therapies. In this study, we show that aldehyde dehydrogenase (ALDH) activity is indicative of radioresistant prostate progenitor cells with an enhanced DNA repair capacity and activation of epithelial-mesenchymal transition (EMT). Gene expression profiling of prostate cancer cells, their radioresistant derivatives, ALDH(+) and ALDH(-) cell populations revealed the mechanisms, which link tumor progenitors to radioresistance, including activation of the WNT/β-catenin signaling pathway. We found that expression of the ALDH1A1 gene is regulated by the WNT signaling pathway and co-occurs with expression of β-catenin in prostate tumor specimens. Inhibition of the WNT pathway led to a decrease in ALDH(+) tumor progenitor population and to radiosensitization of cancer cells. Taken together, our results indicate that ALDH(+) cells contribute to tumor radioresistance and their molecular targeting may enhance the effectiveness of radiotherapy.


PCR amplification of shorter fragments from the devR (Rv3133c) gene significantly increases the sensitivity of tuberculosis diagnosis.
This study was designed to assess the vital issue of gene target length and PCR assay performance in relation to the detection of Mycobacterium tuberculosis in clinical specimens. Two PCR assays that amplify fragments of varying lengths from the devR gene of M. tuberculosis were evaluated. Using M. tuberculosis DNA the 'short-length' PCR assay detected 250-500 genome equivalents vs. 500-1,000 genome equivalents by the 'long-length' assay. In comparison to a highly sensitive smear microscopy test (universal sample processing smear), the sensitivity of the 'short-length' assay was 97.8% vs. 69.9% of the 'long-length' assay in sputum specimens (n=506) from patients being evaluated for a possible diagnosis of tuberculosis. The 27.9% absolute increase in sensitivity was statistically significant (P<0.001). Our results indicate that in a clinical setting when all other conditions are equal, the amplification of a shorter gene fragment of devR increases the sensitivity and efficiency of the PCR assay in spite of using a single copy gene as target.


Activity and concentration of polyphenolic antioxidants in apple juice. 3. Stability during storage.
Kinetic data are reported describing the stability of various classes of polyphenolic antioxidants in an apple juice enriched in these compounds as a function of storage temperature and oxygen concentration. The most thermally sensitive compounds were the various quercetin glycosides and epicatechin, whereas phloridzin and chlorogenic acid were more stable. The quercetin glycosides showed differences in their stability: quercetin galactoside approximately quercetin rhamnoside > quercetin glucoside/rutinoside > quercetin arabinoside. The effect of the presence of oxygen on the degradation rates was clear for only quercetin and to a lesser extent for epicatechin. Accelerated shelf-life testing of enriched apple juice during 4 days at 80 degrees C showed decreases in the antioxidant activity of 20-40%. The parameters obtained were used to predict the stability at different storage conditions. Calculations showed that polyphenolic antioxidants and antioxidant activity of enriched apple juice will be quite stable at ambient or refrigerated storage conditions up to half a year.


Spontaneous gene transfection of human bone cells using 3D mineralized alginate-chitosan macrocapsules.
The effectiveness of nonviral gene therapy remains uncertain because of low transfection efficiencies and high toxicities compared with viral-based strategies. We describe a simple system for transient transfection of continuous human cell lines, with low toxicity, using mineral-coated chitosan and alginate capsules. As proof-of-concept, we demonstrate transfection of Saos-2 and MG63 human osteosarcoma continuous cell lines with gfp, LacZ reporter genes, and a Sox-9 carrying plasmid, to illustrate expression of a functional gene with therapeutic relevance. We show that continuous cell lines transfect with significant efficiency of up to 65% possibly through the interplay between chitosan and DNA complexation and calcium/phosphate-induced translocation into cells entrapped within the 3D polysaccharide based environment, as evidenced by an absence of transfection in unmineralized and chitosan-free capsules. We demonstrated that our transfection system was equally effective at transfection of primary human bone marrow stromal cells. To illustrate, the Sox-9, DNA plasmid was spontaneously expressed in primary human bone marrow stromal cells at 7 days with up to 90% efficiency in two repeats. Mineralized polysaccharide macrocapsules are gene delivery vehicles with a number of biological and practical advantages. They are highly efficient at self-transfecting primary bone cells, with programmable spatial and temporal delivery prospects, premineralized bone-like environments, and have no cytotoxic effects, as compared with many other nonviral systems.


[Is there a voucher for the impact of quality assurance/-improvement methods in foreign countries?].
Internationally, the implementation of diagnosis-related group systems has underlined the importance of quality assurance and improvement in health care systems. Support is expected by various concepts based on different theories and traditions. Published experience and knowledge of other countries with long-standing DRG systems and data in literature are studied to see whether there is an evidence-based impact of quality assurance and quality improvement on health care systems. Relevant data was searched for in the Cochrane-database, the INAHTA-databases DARE, NHSEED and HTA, in DIMDI and the Medline-database of the NIH as well as generally in the internet, addressing the different countries. Several tools of quality assurance and quality improvement like accreditation, evidence-based medicine and guidelines exist in most of the 18 countries studied. Some of them, such as registries and audits, have marked national characteristics. Similar problems in provision of health care are reported internationally. There is broad consensus as to the aspects to be addressed in quality improvement concepts. Though international consensus on effective organization and methods of external assessment is growing there is only limited evidence for efficiency and general applicability of the different tools. Their cost impact, too, has not undergone systematic evaluation. Procedures like feedback strategies and reflection have been identified as having the potenzial to change the practice of health care professionals on a local level, but evidence for system-related impact is missing. Above all, for all concepts of quality improvement there is no real evidence of clinical benefit in the sense of better patient outcomes. None of the various tools for quality improvement in health care proves superior so far. It remains unclear which tool suits best for which intended improvement and in which context. Although quality improvement as a strategy meets with wide approval and appears to be a correct health policy, it remains doubtful whether it really improves clinical outcome and patient-centred health care. Public health research should address these questions. New concepts (e. g. integrating different tools of quality assurance and improvement or DMP systems) need evaluation prior to their broad implementation. Social medicine is called upon to mediate between the consented health care aims of society and medicine.


Is prenatal testosterone-estrogen balance related to critical shoulder angle?
The 2D:4D ratio (an indicator of prenatal testosterone-estrogen balance) is the ratio of the second finger length to the fourth finger length. We hypothesized that low 2D:4D values indicating high prenatal testosterone exposure may be associated with increased critical shoulder angle (CSA). The aim of this study was to evaluate the relationship between CSA and 2D:4D ratio. Meeting the study criteria, 252 patients were included in the study. We measured CSA on true anterior-posterior radiographs, glenoid version(GV) and glenoid inclination(GI) on MRI images and the lengths of the second and fourth fingers on both hands of the patients. Additionally, we compared 2D:4D ratios and CSA, GV, GI measurements. We found a significant negative correlation between CSA and the 2D:4D ratio in both hands (p < 0.001). Patients with CSA > 35° had a significantly lower 2D:4D ratio than patients with CSA < 35° (p < 0.001). When the patients were grouped according to CSA35°, the cut-off value for the left-hand 2D:4D ratio was 0.96, which showed 84.8 % sensitivity and 83.3 % specificity(AUC:0.911). Patients were compared in terms of CSA by categorizing as 2D:4D > 1 and 2D:4D < 1. Accordingly, the CSA value was significantly lower in patients with 2D:4D > 1. In the classification made according to this length classification of the left hand, the cut-off value was 30.25°. This value showed 92.2 % sensitivity and 85 % specificity(AUC:0.956). The 2D:4D ratio is related to CSA. A low 2D:4D ratio(<0.96), indicating high intrauterine testosterone exposure, is associated with CSA > 35°, while a high 2D:4D ratio (>1), indicating low intrauterine testosterone exposure, is associated with a low CSA(<30.25°).


Demonstration of shared antigenic determinants between Streptococcus mutans BHT cell membrane, human heart tissue and myosin using monoclonal antibodies to S. mutans.
Monoclonal antibodies (MAb) raised to intact Streptococcus mutans P-4 cells (serotype e) were used to demonstrate the presence of shared antigenic determinant(s) between S. mutans BHT (serotype b) cell membranes and human heart tissue. MAb binding to both BHT membrane and human heart tissue was demonstrated by ELISA. Common antigens were identified by immunoblot analysis following separation of BHT membrane components and human heart antigens by SDS-PAGE. MAb 22C4 recognized three polypeptides from the BHT membrane preparation, having molecular masses of 42, 56 and 85 kDa. MAb 22C4 also recognized an 85 kDa component and a 200 kDa component from human heart tissue. MAb D159 was specific for a single 82 kDa polypeptide in BHT membrane, and also bound to two high molecular mass components in human heart (165 and 200 kDa). When both MAb D159 and 22C4 were first absorbed with S. mutans P-4 cells, subsequent reactivity to the aforementioned BHT membrane components was inhibited, indicating that these cross-reactive components are found in S. mutans P-4 as well as in S. mutans BHT micro-organisms. Competitive binding analysis showed that both MAb D159 and MAb 22C4 bound to myosin, indicating that S. mutans BHT membrane, human heart tissue and myosin share at least one immunodeterminant. This indicates that myosin could be the cross-reactive tissue component in human heart.


Malnutrition and Gut Microbiota in Children.
Malnutrition continues to threaten the lives of millions across the world, with children being hardest hit. Although inadequate access to food and infectious disease are the primary causes of childhood malnutrition, the gut microbiota may also contribute. This review considers the evidence on the role of diet in modifying the gut microbiota, and how the microbiota impacts childhood malnutrition. It is widely understood that the gut microbiota of children is influenced by diet, which, in turn, can impact child nutritional status. Additionally, diarrhoea, a major contributor to malnutrition, is induced by pathogenic elements of the gut microbiota. Diarrhoea leads to malabsorption of essential nutrients and reduced energy availability resulting in weight loss, which can lead to malnutrition. Alterations in gut microbiota of severe acute malnourished (SAM) children include increased Proteobacteria and decreased Bacteroides levels. Additionally, the gut microbiota of SAM children exhibits lower relative diversity compared with healthy children. Thus, the data indicate a link between gut microbiota and malnutrition in children, suggesting that treatment of childhood malnutrition should include measures that support a healthy gut microbiota. This could be of particular relevance in sub-Saharan Africa and Asia where prevalence of malnutrition remains a major threat to the lives of millions.


[Plastic and reconstructive operations in purulent surgery and traumatology].
The authors propose a complex surgical treatment of extensive purulent wounds and tissue defects based on radical debridement of the pyonecrotic focus, primary and early reconstructive operations. New views on operation "debridement of a purulent wound" were formulated: it is considered as an initial element of the reconstructive surgery. 597 patients with extensive purulent wounds and tissue defects underwent plastic and reconstructive operations with good and satisfactory results in 96.6% of the cases.


Aberrant DNA methylation under conditions of thymine deprivation in Bacillus subtilis.
A study has been made of the levels of 6-methylaminopurine and 5-methyl-cytosine in the DNA of Bacillus subtilis during thymine deprivation. While DNA synthesis was inhibited by thymine deprivation, DNA methylation continued. Base analysis indicated that this aberrant methylation involved an increase solely in the amount of 5-methylcytosine. These aberrant 5-methylcytosine residues were removed from the DNA during continued growth of bacteria in medium lacking thymine. In contrast, 5-methylcytosine residues synthesized during normal growth were relatively unaffected by thymine deprivation. The results are interpreted to indicate that the extensive DNA damage which occurs during thymine deprivation is due in part to exonuclease digestion of regions of DNA containing aberrant 5-methylcytosine residues.


Evaluation of a bivalent (CVD 103-HgR/CVD 111) live oral cholera vaccine in adult volunteers from the United States and Peru.
To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. In the first study, 23 U.S. adult volunteers received CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(8), 10(7), or 10(6) CFU, CVD 111 alone at 10(7) CFU, or placebo. In the second study, 275 Peruvian adults were randomized to receive CVD 103-HgR at 10(9) CFU plus CVD 111 at 10(9) or 10(8) CFU, CVD 111 alone at 10(9) CFU, CVD 103-HgR alone at 10(9) CFU, or placebo. Three of 15 U.S. volunteers who received CVD 111 at 10(7) or 10(8) CFU developed mild diarrhea, compared to none of 4 who received CVD 111 at 10(6) CFU and 1 of 4 who received placebo. Twelve (63%) of 19 vaccine recipients shed the El Tor vaccine strain. All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers. Volunteers who received CVD 111 at 10(7) CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose. In the second study, all dosage regimens were well tolerated in Peruvians. About 20% of volunteers who received CVD 111 at the high dose excreted the El Tor organism, compared to 7% in the low-dose group. CVD 111 was detected in the stools of two placebo recipients, neither of whom had symptoms or seroconverted. In all vaccine groups, 69 to 76% developed fourfold rises in Inaba vibriocidal antibodies. Among those who received the bivalent vaccine, 53 to 75% also developed significant rises in Ogawa vibriocidal antibodies. We conclude that it is feasible to produce a single-dose, oral bivalent vaccine that is safe and immunogenic against both biotypes (El Tor and classical) and both serotypes (Inaba and Ogawa) of cholera for populations in both developed and developing parts of the world.


In vivo detection of dendritic cell antigen presentation to CD4(+) T cells.
Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific T cells has never been directly observed in vivo under conditions where the specificity of the responding T cells for the relevant antigen could be unambiguously assessed. We used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4(+) T cells specific for an OVA peptide-I-Ad complex after adoptive transfer into syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell-rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.


Reversible expression of tryptases and chymases in the jejunal mast cells of mice infected with Trichinella spiralis.
It is has been established that mouse mast cells (MCs) can reversibly alter their expression of serglycin proteoglycans and the homologous granule chymases that have been designated mouse MC protease (mMCP)-1, mMCP-2, and mMCP-5 in vivo. Nevertheless, it remained to be determined whether these immune cells could modify their expression of other chymases and the granule tryptases mMCP-6 and mMCP-7. As assessed immunohistochemically, we now show that MCs reversibly change their expression of the recently described chymase mMCP-9 and both tryptases as these cells traverse the jejunum during the amplification and regression stages of the reactive MC hyperplasia. In noninfected mice, most jejunal MCs reside in the submucosa and express mMCP-6 and mMCP-7, but not mMCP-9 or the chymase mMCP-2. During the inductive phase of the helminth-induced inflammation, when the jejunal MCs move from the submucosa to the tips of the villus, the MCs briefly express mMCP-9, cease expressing mMCP-6 and mMCP-7, and then express mMCP-2. During the recovery phase of the inflammation, jejunal MCs cease expressing mMCP-2 and then express varied combinations of mMCP-6, mMCP-7, and mMCP-9 as they move from the tips of the villus back toward the submucosa. In other model systems, mMCP-6 elicits neutrophil extravasation, and mMCP-7 regulates fibrin deposition and fibrinogen-mediated signaling events. Thus, the ability of a jejunal MC to reversibly alter its tryptase expression during an inflammatory event has important functional implications.


Devolution of hip and knee replacement surgery?
The objectives of this study were to assess trends in referral patterns for joint replacements (JRs) in Ontario between the fiscal year 1988/89 and the fiscal year 1993/94; to assess the redistribution of financial resources if services were provided to residents in the region where they reside; and to estimate the financial implications of the devolution of primary JRs from tertiary-care hospitals to community hospitals. Despite rapid growth in the provision of JRs, there was no significant change in their regional distribution. Community hospitals have increased their share of JRs at the expense of teaching hospitals. For hospitals located in Central east Ontario, the cost of providing JRs to nonresidents increased from $ 5.9 million in 1988/89 to $8.3 million in 1993/94. Devolution of primary JRs requires a minimum reallocation sum of $25.1 million, with potential cost savings of $4.3 million. Many obstacles limit the devolution and local provision of health care services, including modifications to referral patterns and the availability of provider expertise, especially when a substantial redistribution of resources is required. Better clinical data to evaluate outcomes and better patient-specific costing data are required. Devolution of services should be addressed in the context of appropriate institutional compensation for medical education.


Differential fracture response to traumatic brain injury suggests dominance of neuroinflammatory response in polytrauma.
Polytraumatic injuries, specifically long bone fracture and traumatic brain injury (TBI), frequently occur together. Clinical observation has long held that TBI can accelerate fracture healing, yet the complexity and heterogeneity of these injuries has produced conflicting data with limited information on underlying mechanisms. We developed a murine polytrauma model with TBI and fracture to evaluate healing in a controlled system. Fractures were created both contralateral and ipsilateral to the TBI to test whether differential responses of humoral and/or neuronal systems drove altered healing patterns. Our results show increased bone formation after TBI when injuries occur contralateral to each other, rather than ipsilateral, suggesting a role of the nervous system based on the crossed neuroanatomy of motor and sensory systems. Analysis of the humoral system shows that blood cell counts and inflammatory markers are differentially modulated by polytrauma. A data-driven multivariate analysis integrating all outcome measures showed a distinct pathological state of polytrauma and co-variations between fracture, TBI and systemic markers. Taken together, our results suggest that a contralateral bone fracture and TBI alter the local neuroinflammatory state to accelerate early fracture healing. We believe applying a similar data-driven approach to clinical polytrauma may help to better understand the complicated pathophysiological mechanisms of healing.


Predicting gene level sensitivity to JAK-STAT signaling perturbation using a mechanistic-to-machine learning framework.
The JAK-STAT pathway integrates complex cytokine signals via a limited number of molecular components, inspiring numerous efforts to clarify the diversity and specificity of STAT transcription factor function. We developed a computational workflow to make global cytokine-induced gene predictions from STAT phosphorylation dynamics, modeling macrophage responses to IL-6 and IL-10, which signal through common STATs, but with distinct temporal dynamics and contrasting functions. Our mechanistic-to-machine learning model identified select cytokine-induced gene sets associated with late pSTAT3 timeframes and a preferential pSTAT1 reduction upon JAK2 inhibition. We predicted and validated the impact of JAK2 inhibition on gene expression, identifying dynamically regulated genes that were sensitive or insensitive to JAK2 variation. Thus, we successfully linked STAT signaling dynamics to gene expression to support future efforts targeting pathology-associated STAT-driven gene sets. This serves as a first step in developing multi-level prediction models to understand and perturb gene expression outputs from signaling systems.


Dietary choline augments blood choline and cholinergic transmission in terrestrial mollusk Limax maximus.
1. A radioenzymatic assay was used to determine the concentration of choline in the hemolymph of the terrestrial mollusk Limax maximus maintained on choline-enriched and choline-deficient diets. The levels of free choline in the slug's hemolymph varied with the availability of choline in the diet. The concentration of choline in the plasma of choline-enriched animals averaged 5.5 microM while the mean circulating choline level of choline-deprived slugs was 3.3 microM. The difference in choline levels between the two groups was statistically significant. 2. Neurophysiological measurements of transmission at the isolated cholinergic synapses between the salivary burster neuron (SB) and the salivary duct muscle (SD) showed that this synapse was sensitive to fluctuations in the external choline concentration within the physiological range. Increases in exogenous choline from 0.5 to 2.0 microM, from 2.5 to 5.0 microM, and from 5.0 to 15.0 microM were followed by increases in the amplitudes of SB-elicited junction potentials recorded from the SD by a focal extracellular electrode. 3. Thus, the SB-SD synapse is sensitive to the fluctuations in exogenous choline that can occur with a change in diet.


Empirical Findings on the Role of Structured Data, Unstructured Data, and their Combination for Automatic Clinical Phenotyping.
The objective of this study is to explore the role of structured and unstructured data for clinical phenotyping by determining which types of clinical phenotypes are best identified using unstructured data (e.g., clinical notes), structured data (e.g., laboratory values, vital signs), or their combination across 172 clinical phenotypes. Specifically, we used laboratory and chart measurements as well as clinical notes from the MIMIC-III critical care database and trained an LSTM using features extracted from each type of data to determine which categories of phenotypes were best identified by structured data, unstructured data, or both. We observed that textual features on their own outperformed structured features for 145 (84%) of phenotypes, and that Doc2Vec was the most effective representation of unstructured data for all phenotypes. When evaluating the impact of adding textual features to systems previously relying only on structured features, we found a statistically significant (p < 0.05) increase in phenotyping performance for 51 phenotypes (primarily involving the circulatory system, injury, and poisoning), one phenotype for which textual features degraded performance (diabetes without complications), and no statistically significant change in performance with the remaining 120 phenotypes. We provide analysis on which phenotypes are best identified by each type of data and guidance on which data sources to consider for future research on phenotype identification.


Incubation of nicotine seeking is associated with enhanced protein kinase A-regulated signaling of dopamine- and cAMP-regulated phosphoprotein of 32 kDa in the insular cortex.
A recent clinical study demonstrated that damage to the insular cortex can disrupt tobacco addiction. The neurobiological mechanisms for this effect are not yet understood. In this study we used an animal model of nicotine addiction to examine the possibility that changes in insular cortex levels of dopamine (DA)- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a phosphoprotein enriched in DA neurons containing DA D1 receptors, may be associated with changes in vulnerability to nicotine addiction. Once rats acquired self-administration, they were given unlimited access to nicotine (0.01 mg/kg/infusion) for 23 h/day for a total of 10 days. Each infusion was paired with a visual cue (stimulus light) and auditory cue (sound of pump). Nicotine seeking, as assessed under a cue-induced reinstatement paradigm, and markers of DARPP-32 signaling, as assessed using western blot analysis, were examined in separate groups of rats at two different abstinent intervals: 1 and 7 days. Consistent with findings with other drugs of abuse, rats in the 7-day abstinence group took longer to extinguish and responded at higher levels during reinstatement testing as compared with rats in the 1-day reinstatement group. Relative to saline controls, rats in the 7-day but not the 1-day abstinence group had higher levels of DARPP-32 phosphorylated at the protein kinase A site in the insular cortex. These results demonstrate incubation of drug seeking following extended access to nicotine self-administration and suggest that enhanced protein kinase A signaling in the insular cortex via phosphorylation of DARPP-32 at Thr34 is associated with this effect.


Potential of the autopsy.
The autopsy was originally performed to understand anatomy. It still has relevance in correlating physiologic and pathologic processes with anatomic structures. In the first half of this century, it was an important tool in experimental investigations, the discovery of new diseases, and the identification and correlation of known clinical entities with particular cells, tissues, and organs. Since the early 1950s, the autopsy has suffered a regression in terms of interest, the number of competent autopsy physicians and of autopsies, financial reimbursement, and a lack of support from the medical community. Simultaneously its relevance to teaching, the ensuring of accurate diagnoses for therapy, and providing material for the investigation of unique human diseases, has increased. It will take a decade of support to produce a reversal of this trend. The leadership resides in the academic institutions that have the most resources. Academic pathologists could help rejuvenate the autopsy by emphasizing the utilization of human tissue for research and for transplantation, giving new significance to the autopsy and reinforcing its roles in patient care and graduate education.


Caldicellulosiruptor diazotrophicus sp. nov., a thermophilic, nitrogen-fixing fermentative bacterium isolated from a terrestrial hot spring in Japan.
A novel nitrogen-fixing fermentative bacterium, designated as YA01T, was isolated from Nakabusa hot springs in Japan. The short-rod cells of strain YA01T were Gram-positive and non-sporulating. Phylogenetic trees of the 16S rRNA gene sequence and concatenated sequences of 40 single-copy ribosomal genes revealed that strain YA01T belonged to the genus Caldicellulosiruptor and was closely related to Caldicellulosiruptor hydrothermalis 108T, Caldicellulosiruptor bescii DSM 6725T and Caldicellulosiruptor kronotskyensis 2002T. The 16S rRNA gene sequence of strain YA01T shares less than 98.1 % identity to the known Caldicellulosiruptor species. The G+C content of the genomic DNA was 34.8 mol%. Strain YA01T shares low genome-wide average nucleotide identity (90.31-91.10 %), average amino acid identity (91.45-92.10 %) and <70 % digital DNA-DNA hybridization value (41.8-44.2 %) with the three related species of the genus Caldicellulosiruptor. Strain YA01T grew at 50-78 °C (optimum, 70 °C) and at pH 5.0-9.5 (optimum, pH 6.5). Strain YA01T mainly produced acetate by consuming d(+)-glucose as a carbon source. The main cellular fatty acids were iso-C17 : 0 (35.7 %), C16 : 0 (33.3 %), DMA16 : 0 (6.6 %) and iso-C15 : 0 (5.9 %). Based on its distinct phylogenetic position, biochemical and physiological characteristics, and the major cellular fatty acids, strain YA01T is considered to represent a novel species of the genus Caldicellulosiruptor for which the name Caldicellulosiruptor diazotrophicus sp. nov. is proposed (type strain YA01T=DSM 112098T=JCM 34253T).


Tumebacillus ginsengisoli sp. nov., isolated from soil of a ginseng field.
A gram-reaction-positive, rod-shaped, spore-forming bacterium, designated Gsoil 1105(T), was isolated from soil of a ginseng field in Pocheon Province in South Korea and characterized in order to determine its taxonomic position. Comparative analysis of the 16S rRNA gene sequence showed that the isolate belongs to the order Bacillales, showing the highest level of sequence similarity with respect to Tumebacillus permanentifrigoris Eur1 9.5(T) (94.6 %). The phylogenetic distances from other described species with validly published names within the order Bacillales were greater than 9.0 %. Strain Gsoil 1105(T) had a genomic DNA G+C content of 55.6 mol% and menaquinone 7 (MK-7) as the major respiratory quinone. The major fatty acids were iso-C(15 : 0) and anteiso-C(15 : 0). On the basis of its phenotypic properties and phylogenetic distinctiveness, strain Gsoil 1105(T) represents a novel species of the genus Tumebacillus, for which the name Tumebacillus ginsengisoli sp. nov. is proposed. The type strain is Gsoil 1105(T) ( = KCTC 13942(T) = DSM 18389(T)).


A Remote Nutritional Intervention to Change the Dietary Habits of Patients Undergoing Ablation of Atrial Fibrillation: Randomized Controlled Trial.
The Prevention With Mediterranean Diet (PREDIMED) trial supported the effectiveness of a nutritional intervention conducted by a dietitian to prevent cardiovascular disease. However, the effect of a remote intervention to follow the Mediterranean diet has been less explored. This study aims to assess the effectiveness of a remotely provided Mediterranean diet-based nutritional intervention in obtaining favorable dietary changes in the context of a secondary prevention trial of atrial fibrillation (AF). The PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study is a 2-year multicenter, randomized, controlled, single-blinded trial to assess the effect of the Mediterranean diet enriched with extra virgin olive oil (EVOO) on the prevention of atrial tachyarrhythmia recurrence after catheter ablation. Participants in sinus rhythm after ablation were randomly assigned to an intervention group (Mediterranean diet enriched with EVOO) or a control group (usual clinical care). The remote nutritional intervention included phone contacts (1 per 3 months) and web-based interventions with provision of dietary recommendations, and participants had access to a web page, a mobile app, and printed resources. The information is divided into 6 areas: Recommended foods, Menus, News and Online resources, Practical tips, Mediterranean diet classroom, and Your personal experience. At baseline and at 1-year and 2-year follow-up, the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire and a semiquantitative food frequency questionnaire were collected by a dietitian by phone. A total of 720 subjects were randomized (365 to the intervention group, 355 to the control group). Up to September 2020, 560 subjects completed the first year (560/574, retention rate 95.6%) and 304 completed the second year (304/322, retention rate 94.4%) of the intervention. After 24 months of follow-up, increased adherence to the Mediterranean diet was observed in both groups, but the improvement was significantly higher in the intervention group than in the control group (net between-group difference: 1.8 points in the MEDAS questionnaire (95% CI 1.4-2.2; P<.001). Compared with the control group, the Mediterranean diet intervention group showed a significant increase in the consumption of fruits (P<.001), olive oil (P<.001), whole grain cereals (P=.002), pulses (P<.001), nuts (P<.001), white fish (P<.001), fatty fish (P<.001), and white meat (P=.007), and a significant reduction in refined cereals (P<.001), red and processed meat (P<.001), and sweets (P<.001) at 2 years of intervention. In terms of nutrients, the intervention group significantly increased their intake of omega-3 (P<.001) and fiber (P<.001), and they decreased their intake of carbohydrates (P=.02) and saturated fatty acids (P<.001) compared with the control group. The remote nutritional intervention using a website and phone calls seems to be effective in increasing adherence to the Mediterranean diet pattern among AF patients treated with catheter ablation. ClinicalTrials.gov NCT03053843; https://www.clinicaltrials.gov/ct2/show/NCT03053843.


Testosterone replacement therapy following the diagnosis of prostate cancer: outcomes and utilization trends.
Late-onset hypogonadism may impair quality of life and contribute to metabolic and cardiovascular comorbidity in aging men. Testosterone replacement therapy is effective in treating hypogonadism. However, for the millions of men with a history of prostate cancer, exogenous testosterone has long been considered contraindicated, even though little data in such men are available. Clarification of this safety issue could allow treatment to be considered for a sizeable segment of the aging male population. The aim of this study is to examine population-based utilization and impact of testosterone replacement therapy in men with prostate cancer. Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 1181 (0.79%) men received exogenous testosterone following their cancer diagnosis. We used propensity scoring analysis to examine the effect of testosterone replacement on the use of salvage hormone therapy and overall and prostate cancer-specific mortality. We assessed overall mortality, cancer-specific mortality, and the use of salvage hormone therapy. Following prostate cancer diagnosis, testosterone replacement was directly related to income and educational status and inversely related to age (all P < 0.001). Men undergoing radical prostatectomy and men with well-differentiated tumors were more likely to receive testosterone (all P < 0.001). On adjusted analysis, testosterone replacement therapy was not associated with overall or cancer-specific mortality or with the use of salvage hormone therapy. In this population-based observational study of testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality. These findings suggest testosterone replacement therapy may be considered in men with a history of prostate cancer, but confirmatory prospective studies are needed.


Modeling phosphorus concentrations in Irish rivers using land use, soil type, and soil phosphorus data.
Modeling diffuse phosphorus (P) loss may indicate management strategies to minimize P loss from agricultural sources. An empirical model predicting flow-weighted phosphorus concentrations (MRP) was derived using data collected from 35 Irish river catchments. Monitoring records of riverine P and stream flow data were used to calculate MRP values averaged for the years 1991-1994. These data were modeled using land use, soil type, and soil P data. Soil type in catchments was described using soil survey classifications weighted according to their P desorption properties from laboratory results. Soil test P concentrations for the studied watersheds were obtained from a national database. Soil P levels were weighted based on the results of field experiments measuring P losses in overland flow from fields at different soil test P levels. The 35 catchments were statistically clustered into two populations (A and B) based on differences in soil type, specifically, soil hydrology. Catchments in Cluster A had predominantly poorly drained soils and comparatively higher MRP concentrations (0.03-0.17 mg L(-1)) than Cluster B areas (0.01-0.7 mg L(-1)) with mostly well-drained soils. Regression equations derived for A and B type catchments predicted MRP values with 68 and 62% of the variation explained in the models, respectively. Data extracted for the rest of the country were applied to the models to delineate areas at risk on a national scale. While the models were only moderately accurate they highlighted the influence of land management, specifically, high production grassland receiving high P inputs, in conjunction with the effect of soil type and soil hydrology on the transport of P to surface waters.


Active-constructive-interactive: a conceptual framework for differentiating learning activities.
Active, constructive, and interactive are terms that are commonly used in the cognitive and learning sciences. They describe activities that can be undertaken by learners. However, the literature is actually not explicit about how these terms can be defined; whether they are distinct; and whether they refer to overt manifestations, learning processes, or learning outcomes. Thus, a framework is provided here that offers a way to differentiate active, constructive, and interactive in terms of observable overt activities and underlying learning processes. The framework generates a testable hypothesis for learning: that interactive activities are most likely to be better than constructive activities, which in turn might be better than active activities, which are better than being passive. Studies from the literature are cited to provide evidence in support of this hypothesis. Moreover, postulating underlying learning processes allows us to interpret evidence in the literature more accurately. Specifying distinct overt activities for active, constructive, and interactive also offers suggestions for how learning activities can be coded and how each kind of activity might be elicited.


[Functional and electromyographic long-term results following primary microsurgical repair of the recurrent laryngeal nerve].
Six patients with unilateral recurrent nerve paralysis underwent phoniatric follow-up after neurolysis or primary microsurgical repair of the recurrent laryngeal nerve. Four patients were controlled by electromyography of the vocal muscle 14 to 80 months post-operatively. In six patients the paralyzed vocal cords were in median to paramedian position with sustained muscle tonus. Phoniatric parameters were found to be close to the average range in healthy persons. EMG findings indicated degenerative neurogenous paralyses in two patients, signs of reinnervation in another. In one case biphasic action potentials could be recorded.


Rainfall simulation and Structure-from-Motion photogrammetry for the analysis of soil water erosion in Mediterranean vineyards.
Soil water erosion is a serious problem, especially in agricultural lands. Among these, vineyards deserve attention, because they constitute for the Mediterranean areas a type of land use affected by high soil losses. A significant problem related to the study of soil water erosion in these areas consists in the lack of a standardized procedure of collecting data and reporting results, mainly due to a variability among the measurement methods applied. Given this issue and the seriousness of soil water erosion in Mediterranean vineyards, this works aims to quantify the soil losses caused by simulated rainstorms, and compare them with each other depending on two different methodologies: (i) rainfall simulation and (ii) surface elevation change-based, relying on high-resolution Digital Elevation Models (DEMs) derived from a photogrammetric technique (Structure-from-Motion or SfM). The experiments were carried out in a typical Mediterranean vineyard, located in eastern Spain, at very fine scales. SfM data were obtained from one reflex camera and a smartphone built-in camera. An index of sediment connectivity was also applied to evaluate the potential effect of connectivity within the plots. DEMs derived from the smartphone and the reflex camera were comparable with each other in terms of accuracy and capability of estimating soil loss. Furthermore, soil loss estimated with the surface elevation change-based method resulted to be of the same order of magnitude of that one obtained with rainfall simulation, as long as the sediment connectivity within the plot was considered. High-resolution topography derived from SfM revealed to be essential in the sediment connectivity analysis and, therefore, in the estimation of eroded materials, when comparing them to those derived from the rainfall simulation methodology. The fact that smartphones built-in cameras could produce as much satisfying results as those derived from reflex cameras is a high value added for using SfM.


Anthocyanins from black peanut skin protect against UV-B induced keratinocyte cell and skin oxidative damage through activating Nrf 2 signaling.
Excessive Ultraviolet (UV) irradiation induces skin damage. In the present study, the potential protective activity of anthocyanins (cyanidin-3-O-sophoroside and cyanidin-3-O-sambubioside) from black peanut against skin damage induced by UV-B was evaluated in vitro and in vivo. Treatment with anthocyanins significantly reversed UV-B induced oxidative damage and following apoptotic death in human HaCaT cells. Nuclear-factor-E2-related factor 2 (Nrf 2) was activated by anthocyanins through Nrf 2 protein stabilization and nuclear translocation, along with the expressions of antioxidant responsive element (ARE)- related genes (HO1, GCLC and NOQ1). Nrf 2 knockdown in HaCaT cells by targeted-shRNA plasmid markedly abolished the protective activity of anthocyanins against UV-B irradiation. Additionally, topical application of anthocyanins (5 mg cm-2) inhibited UV-B induced oxidative stress and cell apoptosis in BALB/c mouse skin tissues. The protective effect of anthocyanins can be explained by the regulation of oxidative-stress and the suppression of cell apoptosis through the activation of Nrf-2 by interaction with the MAPK and NF-κB signaling pathways. Our results suggested that anthocyanins from black peanut skin might be used as a potential photochemo-protective agent against UV-B induced skin damage.


Serologic investigation of the prevalence of Chlamydophila psittaci in occupationally-exposed subjects in eastern Sicily.
The aim of the study was to investigate the occurrence of serum antibodies to C. psittaci in workers at 8 stock farms located in a rural area of eastern Sicily. Serum samples from 188 workers and 160 controls were tested for immunoglobulin IgA, IgG and IgM direct against C. psittaci by microimmunofluorescent test (MIF). Seropositive subjects were defined as those with IgG titres of 1:16-1:256, and seronegative subjects as those whose titre was <1:16. To rule out the presence of cross reactive antibodies, testing was also performed for C. trachomatis and C. pneumoniae. A total of 28 (14.9%) subjects studied met the criteria for seropositivity to C. psittaci. Two of the 188 (1.06%) had an IgG titre of 1:32, 16 (8.51%) an IgG titre of 1: 64, 6 (3.19%) an IgG titre of 1:128 and 4 subjects (2.12%) demonstrated an antibody titre of 1:256. The high prevalence rate of C. psittaci antibodies among farmers suggests that this infection is spread in those subjects living in areas with an high percentage employed in rearing activities. The authors stress the importance of carrying out health surveillance in subjects working in close contact with animals receptive to infection, and confirm the need to adopt a serological test, such as MIF as a preventive measure for activities at risk.


[Glycosides from Mussaenda arcuata Lam. ex Poiret leaves].
Fractionation of the methanolic extract of Mussaenda arcuata leaves resulted in the isolation of four flavonoid glycosides and of two phenylpropanoid derivatives. The flavonoids were identified as astragalin 2, isoquercitrin 3, kaempferol-3-O-beta-D-rutinoside 5 and rutin 6 and the two phenylpropanoid derivatives as melilotoside 4 and dihydromelilotoside 1. This latter compound is a novel natural product. The structures of compounds 1-6 have been elucidated on the basis of their spectral data and of those of their acetyl derivatives.


Microsatellite loci in Japanese quail and cross-species amplification in chicken and guinea fowl.
In line with the Gifu University's initiative to map the Japanese quail genome, a total of 100 Japanese quail microsatellite markers isolated in our laboratory were evaluated in a population of 20 unrelated quails randomly sampled from a colony of wild quail origin. Ninety-eight markers were polymorphic with an average of 3.7 alleles per locus and a mean heterozygosity of 0.423. To determine the utility of these markers for comparative genome mapping in Phasianidae, cross-species amplification of all the markers was tested with chicken and guinea fowl DNA. Amplification products similar in size to the orthologous loci in quail were observed in 42 loci in chicken and 20 loci in guinea fowl. Of the cross-reactive markers, 57.1% in chicken and 55.0% in guinea fowl were polymorphic when tested in 20 birds from their respective populations. Five of 15 markers that could cross-amplify Japanese quail, chicken, and guinea fowl DNA were polymorphic in all three species. Amplification of orthologous loci was confirmed by sequencing 10 loci each from chicken and guinea fowl and comparing with them the corresponding quail sequence. The microsatellite markers reported would serve as a useful resource base for genetic mapping in quail and comparative mapping in Phasianidae.


A new indirect method for measurement of sinoatrial conduction time and sinus node return cycle.
We developed a new indirect method for the measurement of sinoatrial conduction time (SACT) and the sinus node return cycle (SRC) with a transvenous catheter technique. Two early premature stimuli, at intervals 50 msec longer than the effective refractory period (ERP), were given to the right atrium. These early stimuli were followed by eight constant stimuli. The interval of the constant stimuli was a little shorter than the basic cycle length (BCL). The return cycle A1Ar was measured and plotted on the abscissa; the next interval ArA3, was measured and plotted on the ordinate. This was called the "base point". A new stimulus, A2, was then added to the train of stimulations, first at a point simultaneous with Ar. It was then shifted toward the last constant stimulus at 10-20 msec intervals until A2 met the ERP. The relationship between A1A2 and A2A3 was obtained by the repetition of the procedures with various A1A2 intervals. It had two zones, compensatory and non-compensatory. We postulate that the atriosinus conduction time of the last of the eight stimuli was equal to that of A2 when the stimulus A2 first captured and reset the sinus nodal pacemaker cells, as indicated by the transition point of the two zones. Based on this supposition, SACT and SRC could be measured as the intervals from the base point to the transition point and from the transition point to the eighth stimulus, respectively.


[Monoclonal antibodies IGR to nuclear antigens of neutrophilic granulocytes of human blood].
Four monoclonal antibodies (Mabs) of series IGR-1 and IGR-2 to nuclear antigens of neutrophilic granulocytes of human peripheral blood were obtained. Mabs IGR-1 2B8 and IGR-1 6B5 are bound to their specific antigens in the nuclei of all the investigated human cell lines. These Mabs were also specific for metaphase chromosomes of cell lines HL-60 and U-937. Investigations on the ultrastructural level showed that Mabs IGR-1 6B5 reacted with the HL-60 nuclear heterochromatin region. Mabs IGR-1 3D3 and IGR-2 2F1 manifested high specificity only for the nuclei of mature neutrophils and of plasma cells.


Shape Modulation of Plasmonic Nanostructures by Unconventional Lithographic Technique.
Conventional nano-sphere lithography techniques have been extended to the fabrication of highly periodic arrays of sub-wavelength nanoholes in a thin metal film. By combining the dry etching processes of self-assembled monolayers of polystyrene colloids with metal physical deposition, the complete transition from increasing size triangular nanoprism to hexagonally distributed nanoholes array onto thin metal film has been gradually explored. The investigated nano-structured materials exhibit interesting plasmonic properties which can be precisely modulated in a desired optical spectral region. An interesting approach based on optical absorbance measurements has been adopted for rapid and non-invasive inspections of the nano-sphere monolayer after the ion etching process. By enabling an indirect and accurate evaluation of colloid dimensions in a large area, this approach allows the low-cost and reproducible fabrication of plasmonic materials with specifically modulated optical properties suitable for many application in biosensing devices or Raman enhanced effects.


Reactions of the Escherichia coli flavohaemoglobin (Hmp) with NADH and near-micromolar oxygen: oxygen affinity of NADH oxidase activity.
The soluble flavohaemoglobin (Hmp) of Escherichia coli, product of the hmp gene, contains haem B and FAD in a single polypeptide of molecular mass 44 kDa. The function of this protein (and of the similar proteins identified in several bacteria and yeast) is unknown, but the observation that the binding of oxygen to haem modulates the reduction level of FAD has suggested that Hmp could act as an oxygen sensor. Here, stopped-flow, rapid-scan spectroscopy has shown that the oxidized protein reacts rapidly with NADH to form an oxygenated species, even when efforts are made to reduce oxygen concentrations to sub-micromolar levels, suggesting a high affinity for this ligand. As is the case at high oxygen concentrations (130 microM), oxygenated species formation was kinetically and spectrally heterogeneous. Between 12 ms and 1 s after mixing, following transient formation of the deoxy form and its reaction with dioxygen, a steady-state level of the oxygenated species was attained. During the oxygenated steady state, the flavin remained largely oxidized, as observed previously at 130 microM oxygen. Hmp is an NADH oxidase; on exhaustion of oxygen by reduction (in < 10 s under these conditions), the oxygenated species disappeared to generate the deoxy Fe(II) haem, whereupon the flavin was reduced. The affinity for oxygen during NADH oxidation was measured by continuous dual-wavelength monitoring of the deoxygenation of oxymyoglobin. The Km for oxygen was 2.6 microM, much higher than the Km values determined, using the same method, for the membrane-bound terminal oxidases cytochromes bo' and bd. These results show that the oxidase activity of Hmp, but not necessarily oxygen binding, would be minimal at oxygen concentrations that limit terminal oxidase function.


The interaction between alpha-methyl-dopa and tricyclic antidepressants.
The central hypotensive action of alpha-methyl-DOPA is antagonized by tricyclic antidepressants like desipramine and imipramine. This antagonism has been demostrated in chloralose-anaesthetized cats. The drugs to be tested were infused into the left vertebral artery. The antagonism pProbably takes place in the pons-medulla region of the CNS. Probably, the alpha-adrenolytic properties of the tricyclic antidepressants bring about the blockade of central alpha-adrenergic receptors that are stimulated by alpha-methyl-noradrenaline, the biotransformation product of alpha-methyl-DOPA.


Spatial orientation and the representation of space with parietal lobe lesions.
Damage to the human parietal cortex leads to disturbances of spatial perception and of motor behaviour. Within the parietal lobe, lesions of the superior and of the inferior lobule induce quite different, characteristic deficits. Patients with inferior (predominantly right) parietal lobe lesions fail to explore the contralesional part of space by eye or limb movements (spatial neglect). In contrast, superior parietal lobe lesions lead to specific impairments of goal-directed movements (optic ataxia). The observations reported in this paper support the view of dissociated functions represented in the inferior and the superior lobule of the human parietal cortex. They suggest that a spatial reference frame for exploratory behaviour is disturbed in patients with neglect. Data from these patients' visual search argue that their failure to explore the contralesional side is due to a disturbed input transformation leading to a deviation of egocentric space representation to the ipsilesional side. Data further show that this deviation follows a rotation around the earth-vertical body axis to the ipsilesional side rather than a translation towards that side. The results are in clear contrast to explanations that assume a lateral gradient ranging from a minimum of exploration in the extreme contralesional to a maximum in the extreme ipsilesional hemispace. Moreover, the failure to orient towards and to explore the contralesional part of space appears to be distinct from those deficits observed once an object of interest has been located and releases reaching. Although patients with neglect exhibit a severe bias of exploratory movements, their hand trajectories to targets in peripersonal space may follow a straight path. This result suggests that (i) exploratory and (ii) goal-directed behaviour in space do not share the same neural control mechanisms. Neural representation of space in the inferior parietal lobule seems to serve as a matrix for spatial exploration and for orienting in space but not for visuomotor processes involved in reaching for objects. Disturbances of such processes rather appear to be prominent in patients with more superior parietal lobe lesions and optic ataxia.


Hydration for Adult Patients with Nephrolithiasis: Specificities and Current Recommendations.
Nephrolithiasis affects around 10% of the population and is frequently associated with impaired dietary factors. The first one is insufficient fluid intake inducing reduced urine volume, urine supersaturation, and subsequently urinary lithiasis. Kidneys regulate 24 h urine volume, which, under physiological conditions, approximately reflects daily fluid intake. The aim of this study is to synthesize and highlight the role of hydration in the treatment of nephrolithiasis. Increasing fluid intake has a preventive effect on the risk of developing a first kidney stone (primary prevention) and also decreases the risk of stone recurrence (secondary prevention). Current guidelines recommend increasing fluid intake to at least at 2.5 L/day to prevent stone formation, and even to 3.5-4 L in some severe forms of nephrolithiasis (primary or enteric hyperoxaluria or cystinuria). Fluid intake must also be balanced between day and night, to avoid urinary supersaturation during the night. Patients should be informed and supported in this difficult process of increasing urine dilution, with practical ways and daily routines to increase their fluid intake. The liquid of choice is water, which should be chosen depending on its composition (such as calcium, bicarbonate, or magnesium content). Finally, some additional advice has to be given to avoid certain beverages such as those containing fructose or phosphoric acid, which are susceptible to increase the risk of nephrolithiasis.


Zinc deficiency induced by the chelating agent DTPA and its regulatory interpretation for developmental toxicity classification.
Aminocarboxylic acid (ethylenediamine-based) chelating agents such as DTPA are widely used in a variety of products and processes. Recently, DTPA was classified in the European Union as a developmental toxicant CLP Category 1B. However, according to the CLP regulation (CLP, 2008) classification as a developmental toxicant requires a chemical to possess an intrinsic, specific property to do so. This paper provides overwhelming evidence that shows the developmental toxicity only seen at a sustained high dose of 1000 mg DTPA/kg bw/day in rats during pregnancy is mediated by zinc depletion which leads to non-specific secondary effects associated with zinc deficiency. Therefore, based on the CLP regulation itself, viz. the lack of a specific, intrinsic property, supported by significant differences in zinc kinetics and physiology between pregnant rats and pregnant women, DTPA should not be classified as a developmental toxicant. Moreover, classification for developmental toxicity resulting from zinc deficiency, and only observed at high doses, would not increase protection of human health; instead, it will only lead to onerous and disproportionate restrictions being placed on the use of this substance.


A review of the impact of shelter design on the health of displaced populations.
There are currently millions of displaced people encamped in low-quality shelters that jeopardise the health of these displaced populations. These shelters, which exhibit poor thermal regulation and air quality, are often inhabited by households for several years. Recently, the internal environment of shelters has been recognised as a determinant of the health of the occupants and the indoor air quality (IAQ) and internal temperatures have been identified as critical factors affecting occupants' health. Attempts by researchers and private companies to develop healthier shelter solutions have mainly prioritised factors such as rapid deployment, transportability and sustainability. Via a systematic bibliometric analysis of the existing literature, this review examines the impact of shelters' internal environment on occupant health. Self-reports and building simulation are the most common methodologies reported in the literature, but there is a disconnect between the reported shelter issues and their impact on health. This is likely due to the multifaceted and site-specific factors analysed. Indoor air quality, thermal comfort and overcrowding are the most commonly identified shelter issues, which are strongly related to the presence of infectious and airborne diseases. An analysis of the available literature indicates that there is still a lack of clear guidance linking shelter quality to health. Moreover, evidence of the impact of shelters on health is harder to find, and there is a gap regarding the metrics and the methodology used to evaluate shelter quality. Therefore, further research is necessary to provide evidence of the impact of shelter design on health through transdisciplinary approaches.


Stimulation of mutases and isomerases by vanadium.
The effects of vanadate and vanadate complexes on the rates of exchange of phosphoryl groups in the reactions catalyzed by the enzymes phosphoglucomutase and the coupled system formed by phosphoglycerate mutase and enolase, and the effects of vanadyl complexes on the interconversion of aldehyde and keto groups catalyzed by the enzymes phosphomannose isomerase, phosphoribose isomerase, and phosphoglucose isomerase, were measured using one-dimensional 31P nuclear magnetic resonance spectroscopy. Chemical exchange was investigated by observing the transfer of magnetization achieved by selective irradiation of resonances using the DANTE pulse sequence. The presence of vanadium stimulated the catalytic activity of the enzymes in vitro, with the exception of enolase whose activity was not affected. Addition of vanadate also increased the rate constants of the interconversion of glucose 6-phosphate and fructose 6-phosphate in hemolysates. 51V nuclear magnetic resonance spectroscopy and electron paramagnetic resonance spectroscopy were employed to investigate the interactions between ammonium vanadate and sugar phosphates and the formation of vanadium--sugar phosphate complexes that may be involved in the stimulation of the catalytic activity of the isomerases.


The Role of Volatile Organic Compounds and Rhizosphere Competence in Mode of Action of the Non-pathogenic Fusarium oxysporum FO12 Toward Verticillium Wilt.
Verticillium wilts caused by Verticillium spp. are among the most challenging plant diseases to control and affect numerous hosts worldwide. Due to the lack of effective, conventional control methods, integrated control strategies provide a promising approach to manage these diseases. The non-pathogenic Fusarium oxysporum strain FO12 was reported in previous studies to be an effective biocontrol agent against Verticillium dahliae, however, its mode of action remains to be elucidated. In this study, complementary in vitro and in vivo experiments were conducted in order to explore the implications of inhibitory substances and rhizosphere competence in antagonistic effects of FO12 against V. dahliae and V. longisporum. Volatile organic compounds and soluble substances produced by FO12, which caused significant inhibition of mycelial growth and microsclerotia viability in the two tested Verticillium species, were identified by means of gas and liquid chromatography-mass spectrometry. We showed that the antagonistic effect of F. oxysporum FO12 is partially due to the production of bioactive compounds such as 3-methyl-1-butanol and 2-methyl-1-butanol, among others. Several metabolic pathways of FO12 were altered upon contact with V. dahliae ELV22 volatiles. The reduced production of alpha, alpha-trehalose, a metabolite used in starch and sucrose metabolism, suggests that the biocontrol agent activates its stress response in the presence of the phytopathogen. Microscopic analysis using sGFP-tagged FO12 on oil seed rape as a model plant suggests that the biocontrol strain is an efficient root colonizer, which could compete with V. dahliae in the same ecological niche. The findings obtained in this study provide new insights into the mode of action of this potential biocontrol agent, which are relevant for controlling Verticillium wilt through an ecologically friendly approach.


[Wernicke-Korsakoff syndrome at the Rikshospitalet in 1979-1988. A retrospective study].
Wernicke encephalopathy and Korsakoff psychosis are two facets of the same disease with well-determined cerebral lesions caused by thiamine deficiency. The disease occurs mainly in alcoholics, but other conditions (malabsorption or severe malnutrition) also predispose to the risk of Wernicke-Korsakoff syndrome. The incidence in Denmark is unknown. In the period 1.1.1979-31.12.1988, 24 patients (18 men and six women) were discharged from Rigshospitalet with the diagnosis Wernicke encephalopathy or Korsakoff psychosis. This represents about 0.05% of all admissions in the period. Eighteen out of the 24 cases (75%) were admitted in the past three years (1986-88). The mean age was 55 years. Twenty patients admitted alcohol abuse. The presenting symptoms and the patients' complaints showed great variety and were often related to other alcoholic complications, which could mask the disease. The classic symptom combination: eye movement abnormalities- ataxia and disorders of consciousness were found in seven patients (29%). Sixteen patients had disorders of consciousness or orientation. All the patients were treated with thiamine. The eye-movement disorder has recovered in eight out of ten known cases (80%), nystagmus--in six out of seven cases (86%) while ataxia, disorders of orientation and confabulation recovered in about 50% of cases. The average duration of hospitalisation was 50 days. Altogether nine patients died during the observation period. The condition is most probably underdiagnosed and the traditional diagnostic criteria are considered too rigid. The diagnosis should be considered in alcoholics who present even only one of the classical symptoms and in patients with alcohol dementia. Thiamine should be given on wide indications.


Association Between EEG Patterns and Serum Neurofilament Light After Cardiac Arrest: A Post Hoc Analysis of the TTM Trial.
EEG is widely used for prediction of neurologic outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explored the association between EEG and neurofilament light (NfL) as a marker of neuroaxonal injury, evaluated whether highly malignant EEG patterns are reflected by high NfL levels, and explored the association of EEG backgrounds and EEG discharges with NfL. We performed a post hoc analysis of the Target Temperature Management After Out-of-Hospital Cardiac Arrest trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours postarrest. Patients who awoke or died prior to 36 hours postarrest were excluded. EEG experts blinded to clinical information classified EEG background, amount of discharges, and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NfL after trial completion. The highest available concentration at 48 or 72 hours postarrest was used. A total of 262/939 patients with EEG and NfL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NfL levels than patients with malignant patterns and NfL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI 1.4-6.1 and 6.5-26.2, respectively; effect size 0.47; p < 0.001). Both background and the amount of discharges were independently strongly associated with NfL levels (p < 0.001). The EEG background had a stronger association with NfL levels than EEG discharges (R2 = 0.30 and R2 = 0.10, respectively). NfL levels in patients with a continuous background were lower than for any other background (95% CI for discontinuous, burst-suppression, and suppression, respectively: 2.26-18.06, 3.91-41.71, and 5.74-41.74; effect size 0.30; p < 0.001 for all). NfL levels did not differ between suppression and burst suppression. Superimposed discharges were only associated with higher NfL levels if the EEG background was continuous. Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NfL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NfL may be useful to better identify patients misclassified by single methods. ClinicalTrials.gov NCT01020916.


Deep Flexible Sequential (DFS) Model for Air Pollution Forecasting.
Growing metropolitan areas bring rapid urbanization and air pollution problems. As diseases and mortality rates increase because of the air pollution problem, it becomes a necessity to estimate the air pollution density and inform the public to protect the health. Air pollution problem displays contextual characteristics such as meteorological conditions, industrial and technological developments, traffic problem etc. that change from country to country and also from city to city. In this study, we determined PM[Formula: see text] as the target pollutant and designed a new deep learning based air quality forecasting model, namely DFS (Deep Flexible Sequential). Our study uses real world hourly data from Istanbul, Turkey between 2014 and 2018 to forecast the air pollution 4, 12, and 24 hours before. DFS model is a hybrid & flexible deep model including Long Short Term Memory (LSTM) and Convolutional Neural Network (CNN). The proposed model also is capable of generalization with standard and flexible Dropout layers. Through flexible Dropout layer, the model also obtains flexibility to adapt changing window sizes in sequential modelling. Moreover, this model can be applied to other air pollution time series data problems with small modifications on parameters by taking into account the nature of the data set.


A rapidly evolving MYB-related protein causes species isolation in Drosophila.
Matings among different species of animals or plants often result in sterile or lethal hybrids. Identifying the evolutionary forces that create hybrid incompatibility alleles is fundamental to understanding the process of speciation, but very few such alleles have been identified, particularly in model organisms that are amenable to experimental manipulation. We report here the cloning of the first, to our knowledge, Drosophila melanogaster gene involved in hybrid incompatibilities, Hybrid male rescue (Hmr). Hmr causes lethality and female sterility in hybrids among D. melanogaster and its sibling species. We have found that Hmr encodes a protein with homology to a family of MYB-related DNA-binding transcriptional regulators. The HMR protein has evolved both amino acid substitutions and insertions and deletions at an extraordinarily high rate between D. melanogaster and its sibling species, including in its predicted DNA-binding domain. Our results suggest that hybrid lethality may result from disruptions in gene regulation, and we also propose that rapid evolution may be a hallmark of speciation genes in general.


Long non-coding RNA KCNQ1OT1 mediates the growth of hepatocellular carcinoma by functioning as a competing endogenous RNA of miR-504.
Accumulating evidence highlights the fact that long non‑coding RNAs (lncRNAs) serve as critical factors in the growth of hepatocellular carcinoma (HCC). The dysregulation of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) has been reported in numerous human benign diseases. However, the role of KCNQ1OT1 in human HCC remains poorly understood. In this study, we demonstrated that the expression of KCNQ1OT1 was abnormally increased in HCC tissues. The ectopic high expression of KCNQ1OT1 was associated with liver cirrhosis, a larger tumor size, an advanced TNM stage, and a worse overall survival and tumor‑free survival. For the first time, to the best of our knowledge, we report that KCNQ1OT1 knockdown results in a decreased cell viability and colony formation ability, and an increased rate of apoptosis in vitro. The results from our in vivo results demonstrated that KCNQ1OT1 silencing attenuated tumor growth by impairing cell proliferation. Additionally, we found that KCNQ1OT1 exerted its effects partly by relying on the microRNA‑504 (miR‑504)‑mediated regulation of cyclin‑dependent kinase 16 (CDK16), in addition to the regulation of the glycogen synthase kinase 3β (GSK3β)/β‑catenin/Bcl‑2 signaling pathway. The present study revealed the functions and mechanisms of action of lncRNA KCNQ1OT1 regarding its role in promoting the growth of HCC. Thus, lncRNA KCNQ1OT1 may prove to be a potential therapeutic target for human HCC.


The formation mechanism of fluorescent metal complexes at the Li(x)Ni(0.5)Mn(1.5)O(4-δ)/carbonate ester electrolyte interface.
Electrochemical oxidation of carbonate esters at the Li(x)Ni(0.5)Mn(1.5)O(4-δ)/electrolyte interface results in Ni/Mn dissolution and surface film formation, which negatively affect the electrochemical performance of Li-ion batteries. Ex situ X-ray absorption (XRF/XANES), Raman, and fluorescence spectroscopy, along with imaging of Li(x)Ni(0.5)Mn(1.5)O(4-δ) positive and graphite negative electrodes from tested Li-ion batteries, reveal the formation of a variety of Mn(II/III) and Ni(II) complexes with β-diketonate ligands. These metal complexes, which are generated upon anodic oxidation of ethyl and diethyl carbonates at Li(x)Ni(0.5)Mn(1.5)O(4-δ), form a surface film that partially dissolves in the electrolyte. The dissolved Mn(III) complexes are reduced to their Mn(II) analogues, which are incorporated into the solid electrolyte interphase surface layer at the graphite negative electrode. This work elucidates possible reaction pathways and evaluates their implications for Li(+) transport kinetics in Li-ion batteries.


Step method: a new synthesis method for the design of optical filters with intermediate refractive indices.
We propose a new synthesis method for the design of multilayer optical filters with intermediate refractive indices, the step method. This method consists in adding infinitesimally small index steps in the index profile at optimal positions and then reoptimizing the thickness and the refractive index of the layers. Application of the method to the design of an antireflective coating, a low-pass edge filter, and an immersed polarizing beam splitter shows that it provides interesting solutions, even in the absence of a proper starting design. The formalism developed for the method also serves to demonstrate that the optimal filter consists of either homogeneous layers that maximize the effective refractive index contrast, or of graded-index layers.


Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.
Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules). We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.


Differences in the Concentration of Anti-SARS-CoV-2 IgG Antibodies Post-COVID-19 Recovery or Post-Vaccination.
At the end of 2020, population-based vaccination programs with new generation mRNA-based vaccines began almost all over the world. The aim of the study was to evaluate the titer of anti-SARS-CoV-2 IgG antibodies against the S1 subunit of the virus's spike protein as a marker of the humoral response in 477 patients and the concentration of interferon-gamma as an indicator of cellular response in 28 individuals. In our studies, we used serological enzyme-linked immunosorbent assays. IgG was measured in weeks 2 and 3 after the first dose and 1-5 weeks after the second dose of an mRNA vaccine in seropositive and seronegative individuals as well as in symptomatic and asymptomatic convalescents. High levels of antibodies were observed in 98% of our vaccinated cohort, and the presence of protective T cells was confirmed in the blood samples of all participants. The humoral immune response is diversified and is visible as early as 2-3 weeks after the first dose of the mRNA vaccine. The level of protection increased significantly after the second dose, with the increase being much greater in pre-vaccine healthy subjects and less in convalescents. In the second and third weeks after the second dose, the concentration of IgG antibodies was the highest, and in the following weeks, it decreased gradually. Regular serological measurements on eight subjects show that antibody titers are lower four months after vaccination than before the second dose.


Body composition and muscular strength as predictors of bone mineral density in African American women with metabolic syndrome.
Our cross-sectional study investigated the relationships between regional bone mineral density (BMD) and body composition variables, including total body lean mass (LM) and fat mass (FM), as well as muscular strength in overweight and obese African-American (AA) women with metabolic syndrome (MetS). Forty-four women ranging in age from 39 to 61 years participated. Upper and lower body strength measurements were assessed using chest press and leg extension exercises, respectively. Body composition and BMD of the total body, spine (L2-L4), hip, and radius were measured by dual-energy X-ray absorptiometry. LM was positively correlated with total body, spine, hip, and radius BMD (r = .338-.603, all P < .05), and FM was positively correlated with total body BMD (r = .343, P < .05). In multiple linear regression analyses after controlling for age, height, total energy, and calcium intake, LM was a significant positive determinant of BMD at various skeletal sites (P < .05), while FM was negatively related to BMD of total hip (P < .05). Our results indicate that LM is an independent predictor of total body, spine, hip, and total radius BMD. In contrast, FM is a negative predictor of total body and hip BMD in overweight or obese AA women with MetS (P < .05). Upper and lower body muscular strength measures were not associated with BMD at any skeletal sites. These results suggest an important role for LM in preventing the development of osteopenia and osteoporosis.


Challenges in a product development partnership: a malaria treatment case study.
This paper examines the development of a treatment - a fixed-dose combination of artesunate and mefloquine - in Brazil, from three points of view: in terms of access to medication; to record and report successes; and to look at the lessons learned. This product development took place in the ambit of a public-private partnership. Semi-structured interviews were held with key actors involved in the different phases of the development, and documents were analyzed. Two important points of reference orienting the design of the study and analysis were: a logical model for access to medication; and evaluation of programs. It is concluded that there were several successes over the course of the project, but insufficient attention was given in the project's architecture to planning of adoption of the product: irregularities in demand caused difficulties in planning and production, and adoption of the product was irregular in the Americas. It is concluded that the project can be considered to have been successful: the product was created, and the aims were met - strengthening of institutional and individual capacities and alliances, and advocacy. However, there were weaknesses in the process, which need to be mitigated in future projects of the same type.