A Dynamic Escape Problem of Molecular Motors.
Animal skeletal muscle exhibits very interesting behavior at near-stall forces (when the muscle is loaded so strongly that it can barely contract). Near this physical limit, the myosin II proteins may be unable to reach advantageous actin binding sites through simple attractive forces. It has been shown that the advantageous utilization of thermal agitation is a likely source for an increased force-production capacity and reach in myosin-V (a processing motor protein), and here we explore the dynamics of a molecular motor without hand-over-hand motion including Brownian motion to show how local elastic energy well boundaries may be overcome. We revisit a spatially two-dimensional mechanical model to illustrate how thermal agitation can be harvested for useful mechanical work in molecular machinery inspired by this biomechanical phenomenon without rate functions or empirically inspired spatial potential functions. Additionally, the model accommodates variable lattice spacing, and it paves the way for a full three-dimensional model of cross-bridge interactions where myosin II may be azimuthally misaligned with actin binding sites. With potential energy sources based entirely on realizable components, this model lends itself to the design of artificial, molecular-scale motors.


Novel therapeutic strategies in pancreatic cancer: moving beyond cytotoxic chemotherapy.
Prognosis of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) remains disappointing with a 5-year overall survival of only 3-5%. Compared to other cancers, the evolution in standard therapeutic options has been stagnant and polychemotherapy regimens (with well-known toxicity profile and resistance pattern) remain standard of care. Only for patients (5%-7%) with a breast cancer gene (BRCA) pathogenic germline variant, prognosis has improved by the use of olaparib (poly-ADP ribose polymerase (PARP) inhibitor). This review covers emerging treatment strategies in the management of mPDAC. One of the main topics is the rigid and immunological cold tumor microenvironment (TME) of PDAC and the search for agents that impact this TME and/or engage the immune system. In addition, the use of next-generation sequencing (NGS) has elicited for some patients new targeted therapies directed at alterations in the RTK/RAS/MAPK pathway and the deoxyribonucleic acid (DNA) damage repair pathway. Other evolving treatment strategies are also discussed. The search for new, often combination, treatment strategies for mPDAC should be encouraged and implemented in early treatment lines given the significant decline of performance status of patients in later lines. NGS analysis should be used where available, although cost-effectiveness could be debatable.


Regulation of allergic mucosal sensitization by interleukin-12 gene transfer to the airway.
Expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in the airway allows allergic sensitization to ovalbumin (OVA) in an experimental protocol that others have shown to induce inhalation tolerance. The ensuing response is characterized by T helper (Th)2 cytokines, marked eosinophilia in the bronchoalveolar lavage fluid (BALF) and the tissue, and goblet-cell hyperplasia. These findings, which underscore the importance of the airway microenvironment in the development of immune responses to airborne antigens, prompted us to investigate whether a Type 1 polarized cytokine milieu in the airway would modulate the allergic sensitization. To this end, we concurrently expressed GM-CSF and interleukin (IL)-12 in the airway, using an adenovirus-mediated gene transfer approach. Coexpression of IL-12 did not prevent the development of an antigen-specific immune inflammatory response, but altered its phenotype. Whereas a similar total cell number was observed in the BALF, airway eosinophilia was abrogated. Histologic evaluation of the tissue corroborated the findings in the BALF and demonstrated that IL-12 coexpression prevented goblet-cell hyperplasia. Expression of IL-12 decreased IL-4 and IL-5 content in the BALF by about 80 and 95%, respectively, and IL-5 in the serum by approximately 80%. In contrast, interferon (IFN)-gamma was increased in both BALF and serum. Similarly, we observed a Th2/Th1 shift in OVA-specific cytokine production in vitro. Recall challenge with OVA in vivo after resolution of the initial inflammatory response demonstrated that the effect of IL-12 was persistent. IL-12-mediated inhibition of airway eosinophilia was mainly IFN-gamma-independent, whereas inhibition of OVA-specific IgE synthesis was IFN-gamma-dependent. Our data underscore the importance of the airway microenvironment in the elicitation of immune responses to environmental antigens.


Nephrotic syndrome with mesangial proliferative glomerulonephritis induced by multiple wasp stings.
We report the case of a young male who developed severe nephrotic syndrome within 2-3 weeks after being stung by 3 wasps. A percutaneous kidney biopsy specimen revealed mesangioproliferative glomerulonephritis with occasional subepithelial deposits suggestive of early membranous nephropathy. The patient was treated with oral prednisone 60 mg/day with no significant clinical response after 4 weeks, at which point he was started on oral cyclophosphamide, 100 mg/day, while the prednisone dose was tapered to 20 mg every other day over a 2-week period. Six months after initiation of cyclophosphamide, he still has severe nephrotic syndrome. We also briefly review the literature on Hymenoptera sting associated nephrotic syndrome.


[Various aspects concerning the intensification of bacterial preparation production].
The authors present a classification of the process of cultivation of the microorganisms, which are divided into periodic, quasi-continuous (semi-continuous and multicyclic) and continuous. The advantages of the quasi-continuous processes in comparison with the periodic ones (obtaining the required amount of biomasses at shorter periods) and the continuous ones (no special expensive apparatus is required) are demonstrated. The question on the expediency of organizing the structural subdivision for the cultivation of different microorganism species at the bacterial preparation plants is raised.


Selecting biologically informative genes in co-expression networks with a centrality score.
Measures of node centrality in biological networks are useful to detect genes with critical functional roles. In gene co-expression networks, highly connected genes (i.e., candidate hubs) have been associated with key disease-related pathways. Although different approaches to estimating gene centrality are available, their potential biological relevance in gene co-expression networks deserves further investigation. Moreover, standard measures of gene centrality focus on binary interaction networks, which may not always be suitable in the context of co-expression networks. Here, I also investigate a method that identifies potential biologically meaningful genes based on a weighted connectivity score and indicators of statistical relevance. The method enables a characterization of the strength and diversity of co-expression associations in the network. It outperformed standard centrality measures by highlighting more biologically informative genes in different gene co-expression networks and biological research domains. As part of the illustration of the gene selection potential of this approach, I present an application case in zebrafish heart regeneration. The proposed technique predicted genes that are significantly implicated in cellular processes required for tissue regeneration after injury. A method for selecting biologically informative genes from gene co-expression networks is provided, together with free open software.


Ultra-trace-level determination of polar pesticides and their transformation products in surface and estuarine water samples using column liquid chromatography-electrospray tandem mass spectrometry.
A method is developed for the determination of polar pesticides and their transformation products [atrazine, deethylatrazine, deisopropylatrazine, hydroxyatrazine, diuron, 3,4-dichlorophenylmethylurea, 3,4-dichlorophenylurea (DPU), monuron, bentazone, anthranil-isopropylamide, chloridazon, metolachlor] in surface, estuarine and sea water samples at the low ng/l level. Solid-phase extraction is combined off-line with column liquid chromatography-electrospray ionization tandem mass spectrometric detection (LC-ESI-MS-MS). The applicability of two solid-phase materials, i.e., LiChrolut EN cartridges and graphitized carbon black extraction disks, is evaluated. The influence of the organic solvent used in gradient LC, as well as the amount of co-extracted humic material on the ESI process is studied. The eluotropic strength of the organic solvent was found to have a distinct effect on the sensitivity of ESI-MS if coupled with LC gradient separations. Methanol gave much better results than acetonitrile and phenylurea compounds are more susceptible to solvent changes than triazines. Co-extracted humic material causes signal suppression in ESI-MS-MS detection. The degree of suppression depends upon the sample pH and the nature of the samples, i.e., surface or estuarine water. Detection limits in LC-ESI-MS-MS ranged from 0.2 to 2 ng/l, with the exception of DPU (8 ng/l). The applicability of the procedure was demonstrated by analyzing surface and estuarine water.


Self-assembled peptide beads used as a template for ordered gold nanoparticle superstructures.
Using peptide-based materials to tailor self-assembled, nano-scaled hybrid materials with potentially high biocompatibility/biodegradability is gaining importance in developing a broad range of new applications, in areas such as diagnostics and medicine. Here, we investigated how the self-assembly ability of amphiphilic peptides can be used to create organized inorganic materials, i.e. gold nanoparticles. A bead-forming, purely peptidic amphiphile Ac-[K(Ac)]3-[W-l]3-W-NH2, containing acetylated (Ac) l-lysine (K), l-tryptophan (W) and d-leucine (l), was C-terminally modified with a l-cysteine (C) and linked to gold nanoparticles. Subsequent peptide-driven self-assembly of the peptide-coated gold nanoparticles with increasing water content led to controlled aggregation of the gold-core micelles, forming composite peptide-gold superstructures. The individual gold nanoparticles did not agglomerate but were separated from each other by a peptide film within the composite material, as revealed by electron microscopy studies. Structural investigation on 2D template-stripped gold demonstrated the ability of the peptides to form self-assembled monolayers. Structural elements of β-turns and weak hydrogen bonding of the hydrophobic moiety of the peptide were evident, thereby suggesting that the secondary structure remains intact.


Induction of alveolar type II cell differentiation in embryonic tracheal epithelium in mesenchyme-free culture.
We have previously shown that fetal lung mesenchyme can reprogram embryonic rat tracheal epithelium to express a distal lung phenotype. We have also demonstrated that embryonic rat lung epithelium can be induced to proliferate and differentiate in the absence of lung mesenchyme. In the present study we used a complex growth medium to induce proliferation and distal lung epithelial differentiation in embryonic tracheal epithelium. Day-13 embryonic rat tracheal epithelium was separated from its mesenchyme, enrobed in growth factor-reduced Matrigel, and cultured for up to 7 days in medium containing charcoal-stripped serum, insulin, epidermal growth factor, hepatocyte growth factor, cholera toxin, fibroblast growth factor 1 (FGF1), and keratinocyte growth factor (FGF7). The tracheal epithelial cells proliferated extensively in this medium, forming lobulated structures within the extracellular matrix. Many of the cells differentiated to express a type II epithelial cell phenotype, as evidenced by expression of SP-C and osmiophilic lamellar bodies. Deletion studies showed that serum, insulin, cholera toxin, and FGF7 were necessary for maximum growth. While no single deletion abrogated expression of SP-C, deleting both FGF7 and FGF1 inhibited growth and prevented SP-C expression. FGF7 or FGF1 as single additions to the medium, however, were unable to induce SP-C expression, which required the additional presence of serum or cholera toxin. FGF10, which binds the same receptor as FGF7, did not support transdifferentiation when used in place of FGF7. These data indicate that FGF7 is necessary, but not sufficient by itself, to induce the distal rat lung epithelial phenotype, and that FGF7 and FGF10 play distinct roles in lung development.


Counterpoint.
Claims about alterations in perception based on manipulations of the energetics hypothesis (and other influences) are often framed as interesting specifically because they affect our perceptual experience. Many control experiments conducted on such perceptual effects suggest, however, that they are the result of attribution effects and other kinds of judgmental biases influencing the reporting process rather than perception itself. Schnall (2017, this issue), appealing to Heider's work on attribution, argues that it is fruitless to try to distinguish between perception and attribution. This makes the energetics hypothesis less interesting.


Environmental Liquid Cell Technique for Improved Electron Microscopic Imaging of Soft Matter in Solution.
Liquid-phase transmission electron microscopy is a technique for simultaneous imaging of the structure and dynamics of specimens in a liquid environment. The conventional sample geometry consists of a liquid layer tightly sandwiched between two Si3N4 windows with a nominal spacing on the order of 0.5 μm. We describe a variation of the conventional approach, wherein the Si3N4 windows are separated by a 10-μm-thick spacer, thus providing room for gas flow inside the liquid specimen enclosure. Adjusting the pressure and flow speed of humid air inside this environmental liquid cell (ELC) creates a stable liquid layer of controllable thickness on the bottom window, thus facilitating high-resolution observations of low mass-thickness contrast objects at low electron doses. We demonstrate controllable liquid thicknesses in the range 160 ± 34 to 340 ± 71 nm resulting in corresponding edge resolutions of 0.8 ± 0.06 to 1.7 ± 0.8 nm as measured for immersed gold nanoparticles. Liquid layer thickness 40 ± 8 nm allowed imaging of low-contrast polystyrene particles. Hydration effects in the ELC have been studied using poly-N-isopropylacrylamide nanogels with a silica core. Therefore, ELC can be a suitable tool for in situ investigations of liquid specimens.


Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study.
Experimental pain sensitivity was assessed in individuals with urologic chronic pelvic pain syndrome (UCPPS) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. A series of computer-controlled pressure stimuli were delivered to the thumbnail bed, an asymptomatic site distant from the area of UCPPS pain that is considered to be indicative of overall body pain threshold. Stimuli were rated according to a standardized magnitude estimation protocol. Pain sensitivity in participants with UCPPS was compared with healthy controls and a mixed pain group composed of individuals with other chronic overlapping pain conditions, including fibromyalgia, chronic fatigue, and irritable bowel syndromes. Data from 6 participating MAPP testing sites were pooled for analysis. Participants with UCPPS (n = 153) exhibited an intermediate pain sensitivity phenotype: they were less sensitive relative to the mixed pain group (n = 35) but significantly more sensitive than healthy controls (n = 100). Increased pain sensitivity in patients with UCPPS was associated with both higher levels of clinical pain severity and more painful body areas outside the pelvic region. Exploratory analyses in participants with UCPPS revealed that pain sensitivity increased during periods of urologic symptom flare and that less pressure pain sensitivity at baseline was associated with a greater likelihood of subsequent genitourinary pain improvement 1 year later. The finding that individuals with UCPPS demonstrate nonpelvic pain hypersensitivity that is related to clinical symptoms suggests that central nervous system mechanisms of pain amplification contribute to UCPPS.


Reestablishing public health and land use planning to protect public water supplies.
This study measured the extent to which land use, design, and engineering practices could reduce contamination of major public water supplies. Key parcels of land were identified in New Jersey, and the potential uncontrolled loading of contaminants was estimated with the US Environmental Protection Agency's Long-Term Hydrologic Impact Assessment model for a variety of land use, design, and engineering scenarios. High-density per-acre development and engineering controls, along with housing and light commercial activity near main railroads, would substantially reduce runoff. In New Jersey, government and purveyor action is being taken as a result of, and in support of, these findings.


Clinical Outcomes and Management of NAAT-Positive/Toxin-Negative Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.
Standalone nucleic acid amplification tests (NAATs) are frequently used to diagnose Clostridioides difficile infections (CDI), although they may be unable to distinguish colonization from disease. A two-stage algorithm pairing NAATs with toxin immunoassays (Toxin) may improve specificity. We evaluated clinical outcomes of patients who were NAAT+/Toxin + versus NAAT+/Toxin- and treated versus untreated NAAT+/Toxin- cases through systematic review and meta-analysis. We searched EMBASE and MEDLINE from inception to April 1, 2023 for articles comparing CDI outcomes among symptomatic patients tested by NAAT and Toxin tests. The risk differences (RD) of all-cause mortality and CDI recurrence were computed by random effects meta-analysis between patients who were NAAT+/Toxin + and NAAT+/Toxin-, as well as between patients who were NAAT+/Toxin- and treated or untreated. Twenty-six observational studies comprising 12737 patients were included. 30-Day all-cause mortality was not significantly different between those who were NAAT+/Toxin + (8.4%) and NAAT+/Toxin- (6.7%) (RD = 0.41%, 95%Confidence interval [95%CI]=-0.67, 1.49). Recurrence at 60 days was significantly higher among patients who were NAAT+/Toxin + (19.8%) versus NAAT+/Toxin- (11.0%) (RD = 7.65%, 95%CI = 4.60, 10.71). Among treated compared to untreated NAAT+/Toxin- cases, the all-cause 30-day mortalities were 5.0% and 12.7%, respectively (RD = -7.45%, 95%CI = -12.29, -2.60), but 60-day recurrence was not significantly different (11.6% versus 7.0%, respectively; RD = 5.25%, 95%CI -1.71, 12.22). Treatment of patients who were NAAT+/Toxin- was associated with reduced all-cause mortality, but not recurrence. While subject to the inherent limitations of observational studies, these results suggest that some patients who are NAAT+/Toxin- may benefit from treatment.


Bilateral high-frequency stimulation of the subthalamic nucleus in patients with multiple system atrophy--parkinsonism. Report of four cases.
The aim of this study was to investigate the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in patients with a subtype of multiple system atrophy (MSA) in which levodopa-unresponsive MSA parkinsonism (MSA-P) is predominant. After a local anesthetic was administered, electrodes were stereotactically implanted bilaterally into the STN in four patients with MSA-P and predominantly akinetorigid symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) scores were evaluated preoperatively, at 1 month, and at long-term follow up. At 1 month the median decrease in the UPDRS III motor score was 22 on the 56-point scale (decreases of 16, 13, 29, and 15 points compared with baseline for Cases 1, 2, 3, and 4, respectively). This was mainly due to an improvement in rigidity and akinesia. The median decrease in the UPDRS II score was 11 on the 52-point scale (respective decreases of 5, 7, 13, and 9 points). At 2 years (mean follow up 27 months) there was a median decrease in the UPDRS III score of 12 (respective decreases of 18, 13, 21, and 9 points), and in the UPDRS II score of 5 (with respective decreases of 2, 2, 17, and 2), both compared with the stimulation off state. At long-term follow up there was an increase in the individual Schwab and England scores of 10 to 15% in the stimulation on compared with the stimulation off condition. There was a beneficial effect of STN HFS in these four patients on both a short-term and a long-term basis. A larger prospective study is justified.


Complete Genome Sequence of Escherichia coli Myophage Mangalitsa.
Enteropathogenic Escherichia coli is a prevalent Gram-negative bacterium that can lead to fatal complications from infection in humans. Here, we present the isolation and complete annotation of the 52,329-bp genome of enteropathogenic E. coli ATCC 23545 myophage Mangalitsa. Predicted terminal repeats and temperature sensitivity for plaque formation place Mangalitsa with similar unclassified myoviruses.


Face recognition using the nearest feature line method.
In this paper, we propose a novel classification method, called the nearest feature line (NFL), for face recognition. Any two feature points of the same class (person) are generalized by the feature line (FL) passing through the two points. The derived FL can capture more variations of face images than the original points and thus expands the capacity of the available database. The classification is based on the nearest distance from the query feature point to each FL. With a combined face database, the NFL error rate is about 43.7-65.4% of that of the standard eigenface method. Moreover, the NFL achieves the lowest error rate reported to date for the ORL face database.


Anomalous Orange Light-Emitting (Sr,Ba)2SiO4:Eu(2+) Phosphors for Warm White LEDs.
Phosphors with sufficient red emission component are necessary for warm white light-emitting diodes. In this work on (Sr,Ba)2(1-x)Eu2xSiO4 phosphors, (Sr,Ba)1.5Eu0.5SiO4 achieved 75% of an internal quantum efficiency under excitation by blue light. Surprisingly, the (Sr,Ba)1.5Eu0.5SiO4 exhibited orange emission, against the well-known traditional green-yellow emission of (Sr,Ba)2SiO4:Eu(2+). Moreover, the concentration quenching of Eu(2+) in (Sr,Ba)2SiO4 was abnormally unobvious. With the help of calculations based on the density functional theory, it was discovered that the distinct local environment of luminescence centers rather than usual explanation such as self-absorption or intensified crystal field splitting, is responsible to the interesting red shifts in excitation and emission spectra. The refinement analysis based on X-ray diffraction revealed that the unequal distribution of Eu(2+) to two crystallographic sites caused low concentration of Eu(2+) at the 9-coordination site, inhibiting the concentration quenching. The (Sr,Ba)1.5Eu0.5SiO4 phosphor has warmer emission than the commercial Y3Al5O12:Ce(3+). This study also promotes research on the effect of site occupancy and the local environment of luminescence centers.


The impact of access to addiction specialist on attitudes, beliefs and hospital-based opioid use disorder related care: A survey of hospitalist physicians.
Hospitalizations for complications related to opioid use disorder (OUD) are increasing. Hospitalists care for most hospitalized patients in the United States, yet little is known about their attitudes, beliefs, and clinical practices regarding OUD-related care. Methods: We distributed an online survey to hospitalists in the United States to measure how access to addiction specialists affected attitudes and beliefs regarding hospital-based OUD care, OUD screening practices, naloxone prescribing, and buprenorphine initiation. Results: Among 262 respondents, 67.9% (n = 178) reported having access to addiction specialists. While 84.5% (n = 221) reported often or always caring for patients with OUD, 48.2% (n = 126) rarely or never screened for OUD, 57.1% (n = 149) rarely or never prescribed or recommended naloxone as harm reduction, and 88.9% (n = 233) rarely or never initiated buprenorphine. In multivariable analyses, compared to hospitalists without access to addiction specialists, hospitalist with access to addiction specialists were more likely to feel supported to screen and refer patients to treatment (aOR = 4.4, 95% CI 2.1 - 9.1; ρ < 0.001), to be aware of local treatment resources (aOR = 3.4, 95% CI 1.8 - 6.3; ρ < 0.001), and refer patients to treatment (aOR = 3.0, 95% CI 1.7 - 5.6; ρ < 0.001). Conclusions: Many hospitalists do not provide life-saving treatment to patients with OUD. Access to addiction specialists may increase provision of OUD-related care by hospitalists.


Bilateral pleural effusion complicating umbilical venous catheterization.
Umbilical venous lines are sometimes complicated with pleural and or pericardial effusion, often due to line migration. Bilateral chylous pleural effusion without pericardial effusion in a 28 weeks, extremely low birth infant who was on total parenteral nutrition. Investigations including chest x ray and 2D echocardiogram showed bilateral chylous pleural effusions but appropriate tip position of the umbilical venous line. Removal of the umbilical venous line and cessation of total parenteral nutrition resulted in complete resolution of the pleural effusion. In any newborn with central venous catheter in situ, acute deteriorations specially, those related to pleural and pericardial effusions should alert the clinicians to remove the catheter and should not be misguided by apparently appearing normal correct catheter position by x-ray or 2D echocardiogram.


Induction of T cell immunity by cutaneous genetic immunization with recombinant lentivector.
Recent studies suggest that T cell-based cellular immunity plays an important role in preventing and delaying progression of infectious and neoplastic diseases. Based on these findings, recent efforts in vaccine research are giving rise to a new generation of "T cell" vaccines. The development of T cell vaccines has been problematic. Current investigations are focusing on gene-based immunization strategies, including the development of non-viral "naked" plasmid DNA and recombinant viral vector-based genetic immunization approaches. Here, we briefly review recent progress in the development of recombinant viral vectors for genetic immunization and our own recent studies elucidating differences in mechanisms of genetic immunization. We propose that the mechanism of immune induction depends in part on unique features of specific viral vectors, and that a comparison of representative vectors mechanistically will enable a more informed understanding of the determining parameters of immune induction. Our initial studies have focused on the identification of antigen-presenting-cell subsets important for priming CD8+ T cell immunity, the effects of antigen persistence on immune responses, and the unique immunogenicity of skin as a target tissue for vaccine delivery. We review data suggesting that the unique properties of recombinant lentivectors make them appealing candidates as genetic immunization vehicles for eliciting T cell immune responses.


Lack of a regular source of care among children using a public hospital emergency department.
This study examined risk factors for not having a regular source of care among children presenting to an urban public hospital for nonappointment care. Lack of a regular source of care is associated with decreased use of appropriate health care services and preventive care among children. A cross-sectional survey was conducted for all children less than 16 years of age attending an emergency department at an urban public hospital over a consecutive 7-day period. Univariate and multivariate logistic regression analyses were conducted. In 791 interviews available for analysis, 52% of preschool children and 66% of school-aged children did not have a regular source of care. Children without a regular source of care were more likely to present for nonurgent conditions (P < 0.0005). In multivariate analysis, older age of the child (OR = 1.6, 95% CI 1.132.25), lack of insurance (OR = 1.47, 95% CI 1.03-2.11), and lack of personal vehicle (OR = 1.44, 95% CI 1.05-1.97) were associated with not having a regular source of care. The majority of children using an urban emergency department were without a regular source of care. In this population, no single factor identified children without a regular source of care, but increased age and lack of insurance were associated with it. Addressing this situation will require a multifaceted approach that includes, but is not limited to, decreasing financial barriers.


Anoplocephala perfoliata Infection in Horses in Iceland: Investigation of Associations Between Intensity of Infection and Lesions.
In Iceland, there is at least 1 horse for every 5 human inhabitants, mostly kept on uncultivated rangelands. Although the Icelandic horse is considered robust compared with other breeds, it is nevertheless susceptible to disease. Few studies have investigated the prevalence of intestinal parasites in horses in Iceland. The purpose of this study was to determine the prevalence of the tapeworm, Anoplocephala perfoliata, in horses in Iceland and to explore associations between intensity of infection and the severity of macroscopic pathological lesions in this population. In addition, the relationship between infection and geographical location in Iceland, horse age, and gender were investigated. The utility of a modified McMaster flotation method for identifying infected horses from fecal samples was also studied. The study sample consisted of 104 horses (aged 1-30 yr) slaughtered in 3 abattoirs in North and South Iceland during June and July 2016. The prevalence of A. perfoliata in the horses was 64.4%, with between 1-131 worms found in infected horses. The pathological changes in the horses associated with infection varied from mild (hyperemia in small areas) to severe (large ulcers and necrotic lesions coated with fibrin), and intensity of infection correlated with the size and type of pathological lesions in the intestines. No statistically significant associations between infection with A. perfoliata and geographical location, horse age, or horse gender were detected. The McMaster egg counting method used here was of very low sensitivity (7.4%) and was concluded to be inadequate for detection of A. perfoliata infection in horses. The prevalence of A. perfoliata in horses in Iceland in this study was found to be relatively high compared with results from many studies performed elsewhere in Europe. This may reflect the lack of treatment of horses in Iceland for this parasite, the environmental suitability for the intermediate mite host, and grazing management practices in Iceland. The high prevalence and association with pathology suggest that diagnosis of infection using a sensitive method, along with appropriate treatment, should be considered for horses in Iceland.


Decreased circulating soluble Tie2 levels in preeclampsia may result from inhibition of vascular endothelial growth factor (VEGF) signaling.
Recent studies have found dysregulation in circulating levels of a number of angiogenic factors and their soluble receptors in preeclampsia. In this study, we examined the mechanism of production of soluble Tie2 (sTie2) and its potential connection to the failure of vascular remodeling in preeclamptic pregnancies. Serum samples were collected prospectively from 41 pregnant subjects at five different time points throughout pregnancy. Five of these subjects developed preeclampsia. For a second study, serum and placental samples were collected at delivery from preeclamptic and gestational age-matched controls. We examined serum sTie2 levels, and angiopoietin 1, angiopoietin 2, and Tie2 mRNA expression and localization in placental samples from the central basal plate area. We also examined the effects of vascular endothelial growth factor (VEGF) and a matrix metalloproteinase (MMP) inhibitor on proteolytic shedding of Tie2 in uterine microvascular endothelial cells. Serum sTie2 levels were significantly lower in preeclamptic subjects starting at 24-28 wk of gestation and continued to be lower through the time of delivery. In culture experiments, VEGF treatment significantly increased sTie2 levels in conditioned media, whereas the MMP inhibitor completely blocked this increase, suggesting that VEGF-induced Tie2 release is MMP dependent. Our data suggest, for the first time, an interaction between VEGF and Tie2 in uterine endothelial cells and a potential mechanism for the decrease in circulating sTie2 levels in preeclampsia, likely through inhibition of VEGF signaling. Further studies on VEGF-Tie2 interactions during pregnancy should provide new insights into the mechanisms underlying the failure of vascular remodeling in preeclampsia and other pregnancy complications.


Measurement of antibody to influenza virus neuraminidase by single radial hemolysis in agarose gels.
A simple method of assaying anti-influenza neuraminidase antibodies in human sera was described. Suitable antigenic hybrid viruses were adsorbed to sheep erythrocytes, which were then incorporated into agarose gels. When sera were introduced into wells cut in the gels, zones of hemolysis were observed in the neighborhood of those containing neuraminidase antibodies. There was a direct relationship between zone size and antibody titer. No purification of adsorbed viruses was necessary. The test was rapid, required very simple reagents, gave results that agreed well with those given by conventional techniques, and appeared to be the most sensitive of four methods evaluated. Studies of cross-reactions by hyperimmune sera against homologous and heterologous neuraminidases and of absorption of neuraminidase antibodies from human sera indicated a high degree of specificity. The technique seems to be suitable for large-scale epidemiological investigations.


Pharmacists' perception of their challenges at work, focusing on antimicrobial resistance: a qualitative study from Bangladesh.
Background: The indiscriminate use of antimicrobial medicines has contributed to the development of microorganisms' resistance to antibiotics. Antimicrobial resistance (AMR) is a major global health problem and is most acute in countries that have a weak health care and regulatory system and a high burden of infectious diseases, such as Bangladesh. Due to shortages of physicians available to diagnose and prescribe appropriate antibiotics, people with ailments in Bangladesh are forced to contact various types of health care services, including retail pharmacies, that lack supervision by qualified medical personnel. It is unknown how pharmacists perceive the AMR situation and the related challenges they face.Objective: The aim of the study was to understand retail pharmacist's perceptions regarding AMR.Method: A qualitative study design was used, and in-depth interviews were held with retail pharmacists in Dhaka.Results: The participants demonstrated a variety of concerns regarding AMR. They considered that self-medication, old prescriptions, lack of regulations and supervision, and readily available antibiotics were the main factors that contributed to the misuse of antimicrobial medicines and the development of AMR.Conclusions: To control the further spread of AMR in Bangladesh, there is a need to work at several levels of the health system simultaneously. Initiatives could include establishment of the 'Model Pharmacy' programme nationwide, increasing and widening the focus on AMR in pharmacists' education, ensuring the implementation of government guidelines on AMR, increasing public awareness of the consequences of antimicrobial use, and surveillance and monitoring of regulations and progress. A multipronged strategy is necessary not only for better AMR control but also for investment in a system that is well equipped to provide equitable care in the face of both existing and new health challenges.


[Cholera at the beginning of the XXI century. Prognosis].
The worldwide epidemiological situation in cholera El Tor at the beginning of this century is presented; among its characteristic features are continued extensive epidemics and outbreaks in African and Asian countries with cases of import of this infection to other continents. Outbreaks caused by a new variant of the infective agent of cholera, Vibrio cholerae O139, are still registered at limited territories in the countries of South-East Asia. In some CIS countries (Azerbaijan, Kazakhstan and Russia) unstable situation in cholera is still preserved due to cases of infection import mainly from Asian countries, as well as to the isolation of epidemically insignificant haemolysin-positive and haemolysin-negative V. cholerae O1 and O139, containing no ctx and tcpA genes, from surface water reservoirs and other environmental objects. In Russia prognosis for cholera is still unfavorable.


Designing succinct structural alphabets.
The 3D structure of a protein sequence can be assembled from the substructures corresponding to small segments of this sequence. For each small sequence segment, there are only a few more likely substructures. We call them the 'structural alphabet' for this segment. Classical approaches such as ROSETTA used sequence profile and secondary structure information, to predict structural fragments. In contrast, we utilize more structural information, such as solvent accessibility and contact capacity, for finding structural fragments. Integer linear programming technique is applied to derive the best combination of these sequence and structural information items. This approach generates significantly more accurate and succinct structural alphabets with more than 50% improvement over the previous accuracies. With these novel structural alphabets, we are able to construct more accurate protein structures than the state-of-art ab initio protein structure prediction programs such as ROSETTA. We are also able to reduce the Kolodny's library size by a factor of 8, at the same accuracy. The online FRazor server is under construction.


Eye-tracking correlates of the Implicit Association Test.
Raising awareness of environmental challenges represents an important issue for researchers and scientists. As public opinion remains ambiguous, implicit attitudes toward climate change must be investigated. A custom Single-Category Implicit Association Test, a version of the Implicit Association Test, was developed to assess climate change beliefs. It was administered to 20 subjects while eye movements were tracked using a smart glasses system. Eye gaze patterns were analysed to understand whether they could reflect implicit attitudes toward nature. Recurrence Quantification Analysis was performed to extract 13 features from the eye-tracking data, which were used to perform statistical analyses. Significant differences were found between target stimuli (words related to climate change) and bad attributes in reaction time, and between target stimuli and good attributes in diagonal length entropy, suggesting that eye-tracking may provide an alternative source of information to electroencephalography in modeling and predicting implicit attitudes.


Translation, cultural adaptation and aplication of a pain questionnaire for patients with polycystic kidney disease.
Pain is a common symptom in patients with autosomal dominant polycystic kidney disease (ADPKD), affecting around 60% of cases. Translate a pain questionnaire developed and validated for ADPKD in USA into Portuguese and to perform its cultural adaptation and apply it. The cultural adaptation performed by a panel of experts resulted in small changes consisting of words substitution by synonyms or deletion of terms not commonly used in our culture in 12 out of the 46 questions posed, to solve patients difficulties in understanding the questionnaire. There has been equivalence between the adapted form of the instrument with the back-translation. The final form of the questionnaire applied in 97 patients with ADPKD (64F/33M, 35 ± 12 years) showed that 65 (67%) had isolated or associated pain in multiple locations , more often at lumbar region (77%), followed by abdominal (66%), headache (15%) and chest (4%). The questionnaire revealed that after family history, pain was the second factor contributing to the diagnosis of ADPKD in this population (55% and 22% of cases, respectively). Clinical and laboratory data from medical records showed that patients referring pain had renal volume and size of the largest cyst significantly higher than those without pain. We conclude that the use of a specific pain questionnaire for ADPKD population provided a better characterization of this symptom, as well as its relationship with the associated complications that commonly occur in this setting.


Intradermal adipocytes mediate fibroblast recruitment during skin wound healing.
Acute wound healing in the skin involves the communication of multiple cell types to coordinate keratinocyte and fibroblast proliferation and migration for epidermal and dermal repair. Many studies have focused on the interplay between hematopoietic cells, keratinocytes and fibroblasts during skin wound healing, yet the possible roles for other cell types within the skin, such as intradermal adipocytes, have not been investigated during this process. Here, we identify that adipocyte lineage cells are activated and function during acute skin wound healing. We find that adipocyte precursor cells proliferate and mature adipocytes repopulate skin wounds following inflammation and in parallel with fibroblast migration. Functional analysis of mice with defects in adipogenesis demonstrates that adipocytes are necessary for fibroblast recruitment and dermal reconstruction. These data implicate adipocytes as a key component of the intercellular communication that mediates fibroblast function during skin wound healing.


Association between hydroxycarbamide exposure and neurocognitive function in adolescents with sickle cell disease.
Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease-modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16-17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide (n = 12 HbSC/HbSβ+ thalassaemia; n = 52 HbSS/HbSβ0 thalassaemia) and those never treated with hydroxycarbamide (n = 31 HbSC/HbSβ+ thalassaemia; n = 8 HbSS/HbSβ0 thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSβ thalassaemia: P = 0·036, effect size [d] = 0·65), reaction speed (HbSS/HbSβ0 thalassaemia: P = 0·002, d = 1·70), sustained attention (HbSS/HbSβ0 thalassaemia: P = 0·014, d = 1·30), working memory (HbSC/HbSβ+ thalassaemia: P = 0·034, d = 0·71) and verbal memory (HbSC/HbSβ+ thalassaemia: P = 0·038, d = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSβ0 thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory (P = 0·009) and reading (P = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P = 0·014, MCV: P = 0·006, WBC: P = 0·047) and reading (MCV: P = 0·021, WBC: P = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD.


Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies.
Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.


An in silico strategy for identification of novel drug targets against Plasmodium falciparum.
The apicomplexan parasite Plasmodium falciparum is responsible for global malaria burden. With the reported resistance to artemisinin chemotherapy, there is an urgent need to maintain early phase drug discovery and identify novel drug targets for successful eradication of the pathogen from the host. In our previous work on comparative genomics study for identification of putative essential genes and therapeutic candidates in P. falciparum, we predicted 11 proteins as anti-malarial drug targets from PlasmoDB database. In this paper, we made an attempt for identification of novel drug targets in P. falciparum genome using a sequence of computational methods from Malaria Parasite Metabolic Pathway database. The study reported the identification of 71 proteins as potential drug targets for anti-malarial interventions. Furthermore, homology modeling and molecular dynamic simulation study of one of the potential drug targets, aminodeoxychorismate lyase, was carried to predict the 3D structure of the protein. Structure and ligand-based drug designing reported MMV019742 from Pathogen Box and TCAMS-141515 from GSK-TCAMS library as potential hits. The reliability of the binding mode of the inhibitors is confirmed by GROMACS for a simulation time of 20 ns in water environment. This will be helpful for experimental validation of the small-molecule inhibitor.


Evaluating catchment response to artificial rainfall from four weather generators for present and future climate.
The technical lifetime of urban water infrastructure has a duration where climate change has to be considered when alterations to the system are planned. Also, models for urban water management are reaching a very high complexity level with, for example, decentralized stormwater control measures being included. These systems have to be evaluated under as close-to-real conditions as possible. Long term statistics (LTS) modelling with observational data is the most close-to-real solution for present climate conditions, but for future climate conditions artificial rainfall time series from weather generators (WGs) have to be used. In this study, we ran LTS simulations with four different WG products for both present and future conditions on two different catchments. For the present conditions, all WG products result in realistic catchment responses when it comes to the number of full flowing pipes and the number and volume of combined sewer overflows (CSOs). For future conditions, the differences in the WGs representation of the expectations to climate change is evident. Nonetheless, all future results indicate that the catchments will have to handle more events that utilize the full capacity of the drainage systems. Generally, WG products are relevant to use in planning of future changes to sewer systems.


Near-Infrared-II Nanoparticles for Vascular Normalization Combined with Immune Checkpoint Blockade via Photodynamic Immunotherapy Inhibit Uveal Melanoma Growth and Metastasis.
Photodynamic therapy (PDT) has been widely employed in tumor treatment due to its effectiveness. However, the tumor hypoxic microenvironment which is caused by abnormal vasculature severely limits the efficacy of PDT. Furthermore, the abnormal vasculature has been implicated in the failure of immunotherapy. In this study, a novel nanoparticle denoted as Combo-NP is introduced, composed of a biodegradable NIR II fluorescent pseudo-conjugate polymer featuring disulfide bonds within its main chain, designated as TPA-BD, and the vascular inhibitor Lenvatinib. Combo-NP exhibits dual functionality by not only inducing cytotoxic reactive oxygen species (ROS) to directly eliminate tumor cells but also eliciting immunogenic cell death (ICD). This ICD response, in turn, initiates a robust cascade of immune reactions, thereby augmenting the generation of cytotoxic T lymphocytes (CTLs). In addition, Combo-NP addresses the issue of tumor hypoxia by normalizing the tumor vasculature. This normalization process enhances the efficacy of PDT while concurrently fostering increased CTLs infiltration within the tumor microenvironment. These synergistic effects synergize to potentiate the photodynamic-immunotherapeutic properties of the nanoparticles. Furthermore, when combined with anti-programmed death-ligand 1 (PD-L1), they showcase notable inhibitory effects on tumor metastasis. The findings in this study introduce an innovative nanomedicine strategy aimed at triggering systemic anti-tumor immune responses for the treatment of Uveal melanoma.


Insulin increases cell surface GLUT4 levels by dose dependently discharging GLUT4 into a cell surface recycling pathway.
The insulin-responsive glucose transporter GLUT4 plays an essential role in glucose homeostasis. A novel assay was used to study GLUT4 trafficking in 3T3-L1 fibroblasts/preadipocytes and adipocytes. Whereas insulin stimulated GLUT4 translocation to the plasma membrane in both cell types, in nonstimulated fibroblasts GLUT4 readily cycled between endosomes and the plasma membrane, while this was not the case in adipocytes. This efficient retention in basal adipocytes was mediated in part by a C-terminal targeting motif in GLUT4. Insulin caused a sevenfold increase in the amount of GLUT4 molecules present in a trafficking cycle that included the plasma membrane. Strikingly, the magnitude of this increase correlated with the insulin dose, indicating that the insulin-induced appearance of GLUT4 at the plasma membrane cannot be explained solely by a kinetic change in the recycling of a fixed intracellular GLUT4 pool. These data are consistent with a model in which GLUT4 is present in a storage compartment, from where it is released in a graded or quantal manner upon insulin stimulation and in which released GLUT4 continuously cycles between intracellular compartments and the cell surface independently of the nonreleased pool.


[Formation of the prothrombin-phosphatidyl serine and thrombin-phosphatidyl serine complex].
A possibility of formation of the thrombin-phosphatidyl serine and prothrombin-phosphatidyl serine complex is discussed. Prothrombin incubation with 131J-labelled phosphatidyl serine and its subsequent activation results in a formation of a thrombin-phosphatidyl serine--131J-complex. The radioactive label is also detected in the protein precipitate after thermodenaturation of thrombin preincubated with 131J-labelled phosphatidyl serine, which suggests that thrombin is firmly bound to phosphatidyl serine. The formation of the thrombin-phosphatidyl serine and prothrombin-phosphatidyl serine complex is supported by data of gel-filtration on Sephadex G-200 and acrylexes P-150 and P-60, as well as by differential spectrophotometry.


Risk factors for community acquired urinary tract infections caused by extended spectrum β-lactamase (ESBL) producing Escherichia coli in children: a case control study.
Background: We noted a recent increase in cases of urinary tract infection due to community-acquired ESBL-producing Escherichia coli in children treated at our institution. Risk factors of urinary tract infection due to ESBL-producing E. coli in children in the USA remain unclear. Methods: A single center retrospective case control study of UTI due to CA-ESBL-producing E. coli during a 5-year period (2012-2016). Control cases with non-ESBL-producing E. coli urinary tract infection were matched by age, gender and year of infection. Results: A total of 111 patients with ESBL-producing E coli urinary tract infection and 103 controls were included. The proportion of ESBL-producing E coli urinary tract infection ranged from 7% to 15% of all UTI cases. The distribution of ESBL cases per year: 27 in 2012; 18 in 2013; 22 in 2014; 15 in 2015 and 29 in 2016. Median age was 4 years with female predominance (84%). The ESBL group was predominantly African American (32%) followed by individuals of Middle Eastern ethnic background (31%). Risk factors by univariate analysis were vesicoureteral reflux: (20.9 ESBL group vs 6% controls; p = .002), prior antibiotic usage in the last 3 months (including β-lactams), prior UTI (last 3 months), recent hospitalization (last 3 months) and Middle Eastern ethnic background. However, multivariate analysis showed that only prior antibiotic usage (p = .001) and Middle Eastern ethnic background (p < .001) were independent risk factors. ESBL-producing strains were more frequently resistant to trimethoprim-sulfamethoxazole (72% vs 25%) and ciprofloxacin (73% vs 5%) than strains not producing ESBL. Conclusion: Risk factors for community-acquired ESBL-producing E coli urinary tract in our pediatric patient population were antibiotic usage within the previous 3 months and Middle Eastern ethnic background. This may be related to increased risk of intestinal colonization with resistant bacterial strains.


Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis.
Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1beta expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2(-/-) ApoE(-/-) cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.


Iris sector heterochromia as a marker for neural crest disease.
A 6-month-old female infant with biopsy-proved Hirschsprung's disease had associated sector heterochromia of the irides. The association between sector heterochromia and Hirschsprung's disease has been previously reported and both conditions have been ascribed to neural crest defects. Histologic characteristics of the ocular involvement have not previously been reported, to our knowledge. Histopathologic examination of the globes revealed decreased iris stroma, decreased pigmentation in the anterior stroma, and reduced numbers of pigment-producing cells in the affected areas. Both the ocular and gastrointestinal findings reflect abnormalities in tissues of neural crest origin.


Sex-different association of DAO with schizophrenia in Koreans.
The gene encoding D-amino acid oxidase (DAO), which acts as a receptor for the schizophrenia-associated neurotransmitter, N-methyl-D-aspartate (NMDA), is regarded as a potential candidate gene for schizophrenia. However, the potential association of the DAO gene with schizophrenia has been the subject of some debate. Here, we tested three single nucleotide polymorphisms (SNPs) of DAO in a group of Korean schizophrenia patients, and found no significant association in the overall study subjects. Interestingly, however, we found gender-specific differences in allele distributions, with SNP rs2070586 appearing to act as a risk allele in female schizophrenia patients, but as a protective allele in males. Our data support the hypothesis that DAO plays a role in schizophrenia, possibly in a gender-dependent manner.


Transplant Ureteral Stenosis after Renal Transplantation: Risk Factor Analysis.
The results of kidney transplants have improved dramatically in recent years, leading to reduced morbidity and mortality. Despite continuous improvements, urological complications occur at a rate of 2.6%-15%. Ureteral stenosis of graft ureters is the most common complication, with a probability of 0.5%-6.3%. This study aimed to determine the incidence of ureteral stenosis after kidney transplantation and identify risk factors that distinguish transplant patients with and without ureteral stenosis. This study retrospectively analyzed patients who had undergone kidney transplantation at the Department of Urology of the Friedrich-Alexander University Erlangen-Nuremberg between 2001 and 2015. Forty-seven patients developed ureteral stenosis during the operation. Most of the ureteral stenosis cases occurred in the first 4 months after transplantation. Kaplan-Meier analysis and the log-rank test were used to calculate the cumulative risk, and the Mann-Whitney U test was used nonparametrically. The significance level was set at p < 0.05. Statistical analysis showed that residual diuresis (p = 0.008), cold ischemia time (CIT) (p = 0.040), the body mass index (p = 0.027), and donor serum creatinine value (p = 0.039) showed a significantly different distribution between recipients with or without ureteral stenosis after kidney transplantation. In multivariate Cox's regression modeling, residual diuresis and the donor serum creatinine level were identified as the only independent predictors of patients' stenosis-free survival. Urological complications not diagnosed and treated in time endanger the success of kidney transplantation. After evaluating the kidney transplantation data of the patients at the Transplant Center Erlangen-Nuremberg from 2001 to 2015, residual diuresis, CIT, the body mass index, and donor serum creatinine value were found to influence the development of ureteral stenosis.


Effect of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril.
The role of angiotensin II and kinins on the renal cortical and papillary hemodynamic and on the sodium and water excretory responses to converting enzyme inhibition with captopril was examined in euvolemic Munich-Wistar rats. Cortical and papillary blood flows were measured using a laser Doppler flowmeter. Cortical blood flow increased 28% after blockade of angiotensin II receptors with DuP 753 (2 mg/kg i.v., n = 6). Captopril (2 mg/kg i.v., n = 6) had no effect on cortical blood flow in rats pretreated with the angiotensin II antagonist. DuP 753 had no effect on papillary blood flow, nor did it prevent the rise in papillary blood flow produced by captopril (2 mg/kg, n = 6). Infusion of a kinin receptor antagonist, D-Arg, [Hyp3,Thi5,8,D-Phe7]-bradykinin (2.5 micrograms/min i.v.), reduced basal papillary blood flow by 15% and blocked the rise in papillary blood flow produced by captopril. Renal blood flow rose by 11% after DuP 753 (2 mg/kg, n = 6), and subsequent administration of captopril and the kinin antagonist had no effect on renal blood flow. Urine flow and sodium excretion increased after DuP 753, but captopril produced additional increases in urine flow and sodium excretion of 68% and 46% respectively. Fractional sodium excretion rose from 0.85 +/- 0.15% to 1.56 +/- 0.14% after captopril. Infusion of the kinin antagonist returned sodium and water excretion to control levels, but fractional sodium excretion was not significantly altered. Glomerular filtration rate was not altered by DuP 753 or captopril; however, it fell from 1.6 +/- 0.1 to 1.2 +/- 0.1 ml/min/g kidney wt during infusion of the kinin antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)


Resolution of conflicting assignments for the bovine casein kinase II alpha (CSNK2A2) gene.
The casein kinase II alpha' gene (CSNK2A2), which physically maps to human chromosome 16 (HSA16), has previously been mapped to bovine chromosome 5 (BTA5). Based on these results, a new segment of homology between the human and bovine genomes was suggested. In this paper we demonstrate linkage between CSNK2A2 and several markers on BTA18. Our result is supported by the extensive conservation of synteny between HSA16q and BTA18. Bovine chromosome 18 markers used in this study included several microsatellites, as well as the MC1R gene previously mapped to HSA16q24.3. Sequencing of the PCR-fragment mapped to BTA5 reveals that a CSNK-like retroposon was responsible for the conflicting assignments. The present results further extend the observed conservation of synteny between HSA16q and BTA18.


Child patient behavior: a new perspective.
All behavior depends on responses of the nervous system (Shepherd 1988). Alkon demonstrated physical changes in the nervous systems of Hermissenda crassicornis and rabbits at the molecular level following behavioral conditioning. This physical change resulted in a reduced flow of potassium ions across the neuronal cell membrane for some time, with resultant enhanced excitability during this period. It is suggested that behavioral deterioration in children during sequential dental visits might be the result of a reduced potassium ion flow across the neuronal cell membrane, with resultant enhanced excitability during this period. Alkon also reported that in a "conditioned" stimulus, information flows along a "collateral pathway" formed in the course of the learning experience. It is hypothesized that behavioral improvement in children following positive dental experiences (model learning and desensitization) may be due to the information of the "conditioned" dental stimulus flowing along a "collateral pathway" formed in the course of the learning experience.


Antibiotic Prophylaxis During Dental Procedures in Patients with Prosthetic Joints.
In patients with artificial joints, the need for antimicrobial prophylaxis during dental procedures is often raised. The present document describes the pathogenic mechanisms and epidemiological data on the subject of periprosthetic joint infections (PJI) after dental procedures. The document reflects the opinion and recommendations of the expert group 'Infection' of Swiss Orthopaedics. Microorganisms belonging to oral flora can seed haematogenously to an artificial joint. The proof of a causative relation with dental procedures is not possible, because the responsible bacteraemia can originate from the oral cavity at any time, irrespective of when the dental procedure occurs. Good oral hygiene is associated with a lower risk for PJI. Transient bacteraemia occurs during daily oral hygiene activity (e.g., tooth brushing) and thus the cumulative risk for a haematogenous PJI from tooth brushing is higher than that from a dental procedure. PJI after a dental procedure are rarely reported. On the basis of an epidemiological model, several thousand patients with artificial joints must receive antimicrobial prophylaxis to prevent a single PJI. Considering this ratio, the number of adverse events due to the antimicrobial compound exceeds the benefit of administering it by a large magnitude. Therefore, as a rule for the vast majority of cases, antimicrobial prophylaxis during dental procedures is not recommended. It is important that a patient has a good oral health status before joint implantation and that good oral hygiene is continuously maintained in patients with artificial joints.


Scedosporium apiospermum keratomycosis in a dog.
A 6-year-old male castrated Norfolk Terrier dog was examined following a 21-day history of an increasingly painful eye. Examination revealed marked blepharospasm and purulent ocular discharge associated with an ulcerative keratitis. There was panstromal corneal opacity with raised gray to white lesions. Corneal cytology demonstrated branching septate fungal hyphae identified by polymerase chain reaction as Scedosporium apiospermum. Treatment with topical 1% voriconazole solution was successful in resolving the keratomycosis.


Hemorrhage into the breast.
Hemorrhage into the breast is an unusual complication following anticoagulant therapy. A review has revealed only 20 examples. We wish to report the mammographic features not previously described in the radiologic literature.


Use of autogenous materials in reconstructing the anophthalmic socket.
A variety of autogenous materials may be used for orbital implantation in the anophthalmic socket. An understanding of the pathology of the socket is necessary to treat the problem correctly. Autogenous grafts have been used successfully to treat the superior sulcus deformity, extruding implant, and the contracting socket. The major advantages of autogenous material are its minimal inflammatory reaction and its total compatibility with the host.


An outbreak of Escherichia coli O157:H7 infections associated with leaf lettuce consumption.
In July 1995, 40 Montana residents were identified with laboratory-confirmed Escherichia coli O157:H7 infection; 52 residents had bloody diarrhea without laboratory confirmation. The median age of those with laboratory-confirmed cases was 42 years (range, 4- 86); 58% were female. Thirteen patients were hospitalized, and 1 developed hemolytic-uremic syndrome. A case-control study showed that 19 (70%) of 27 patients but only 8 (17%) of 46 controls reported eating purchased (not home-grown) leaf lettuce before illness (matched odds ratio, 25.3; 95% confidence interval, 3.9-1065.6). Pulsed-field gel electrophoresis identified a common strain among 22 of 23 isolates tested. Implicated lettuce was traced to two sources: a local Montana farm and six farms in Washington State that shipped under the same label. This outbreak highlights the increasing importance of fresh produce as a vehicle in foodborne illness. Sanitary growing and handling procedures are necessary to prevent these infections.


Duplicated Abd-B class genes in medaka hoxAa and hoxAb clusters exhibit differential expression patterns in pectoral fin buds.
Hox genes form clusters. Invertebrates and Amphioxus have only one hox cluster, but in vertebrates, they are multiple, i.e., four in the basal teleost fish Polyodon and tetrapods (HoxA, B, C, D), but seven or eight in common teleosts. We earlier completely sequenced the entire hox gene loci in medaka fish, showing a total of 46 hox genes to be encoded in seven clusters (hoxAa, Ab, Ba, Bb, Ca, Da, Db). Among them, hoxAa, hoxAb and hoxDa clusters are presumed to be important for fin-to-limb evolution because of their key role in forelimb and pectoral fin development. In the present study, we compared genome organization and nucleotide sequences of the hoxAa and hoxAb clusters to these of tetrapod HoxA clusters, and found greater similarity in hoxAa case. We then analyzed expression of Abd-B family genes in the clusters. In the trunk, those from the hoxAa cluster, i.e., hoxA9a, hoxA10a, hoxA11a and hoxA13a, were expressed in a manner keeping the colinearity rule of the hox expression as those of tetrapods, while those from the hoxAb cluster, i.e., hoxA9b, hoxA10b, hoxA11b and hoxA13b, were not. In the pectoral fins, the hoxAa cluster was expressed in split domains and did not obey the rule. By contrast, those from the hoxAb and hoxDa clusters were expressed in a manner keeping the rule, i.e., an ancestral pattern similar to those of tetrapods. It is plausible that this differential expression of the two clusters is caused by changes occurred in global control regions after cluster duplications.


Does verbatim sentence recall underestimate the language competence of near-native speakers?
Verbatim sentence recall is widely used to test the language competence of native and non-native speakers since it involves comprehension and production of connected speech. However, we assume that, to maintain surface information, sentence recall relies particularly on attentional resources, which differentially affects native and non-native speakers. Since even in near-natives language processing is less automatized than in native speakers, processing a sentence in a foreign language plus retaining its surface may result in a cognitive overload. We contrasted sentence recall performance of German native speakers with that of highly proficient non-natives. Non-natives recalled the sentences significantly poorer than the natives, but performed equally well on a cloze test. This implies that sentence recall underestimates the language competence of good non-native speakers in mixed groups with native speakers. The findings also suggest that theories of sentence recall need to consider both its linguistic and its attentional aspects.


Hypersensitive photic responses and intact genome-wide transcriptional control without the KaiC phosphorylation cycle in the Synechococcus circadian system.
Cyanobacteria are unique organisms with remarkably stable circadian oscillations. These are controlled by a network architecture that comprises two regulatory factors: posttranslational oscillation (PTO) and a transcription/translation feedback loop (TTFL). The clock proteins KaiA, KaiB, and KaiC are essential for the circadian rhythm of the unicellular species Synechococcus elongatus PCC 7942. Temperature-compensated autonomous cycling of KaiC phosphorylation has been proposed as the primary oscillator mechanism that maintains the circadian clock, even in the dark, and it controls genome-wide gene expression rhythms under continuous-light conditions (LL). However, the kaiC(EE) mutation (where "EE" represents the amino acid changes Ser431Glu and Thr432Glu), where phosphorylation cycling does not occur in vivo, has a damped but clear kaiBC expression rhythm with a long period. This suggests that there must be coupling between the robust PTO and the "slave" unstable TTFL. Here, we found that the kaiC(EE) mutant strain in LL was hypersensitive to the dark acclimation required for phase shifting. Twenty-three percent of the genes in the kaiC(EE) mutant strain exhibited genome-wide transcriptional rhythms with a period of 48 h in LL. The circadian phase distribution was also conserved significantly in most of the wild-type and kaiC(EE) mutant strain cycling genes, which suggests that the output mechanism was not damaged severely even in the absence of KaiC phosphorylation cycles. These results strongly suggest that the KaiC phosphorylation cycle is not essential for generating the genome-wide rhythm under light conditions, whereas it is important for appropriate circadian timing in the light and dark.


Novel anti-inflammatory compounds from Myrsine seguinii, terpeno-benzoic acids, are inhibitors of mammalian DNA polymerases.
Novel anti-inflammatory compounds, terpeno-benzoic acids, were found from the plant, Myrsine seguinii. The strongest of these anti-inflammatory agents, 3-geranyl-4-hydroxy-5-(3'-methyl-2'-butenyl) benzoic acid (compound 1), showed an inhibitory effect against enzymes involved in replication, such as calf DNA polymerase alpha (pol. alpha), rat DNA polymerase beta (pol. beta) and one of the beta family polymerases, calf thymus terminal deoxynucleotidyl transferase (TdT). The minimum inhibitory concentration (MIC) and IC50 values were 82 and 22 microM for pol. alpha, 86 and 11 microM for pol. beta, 140 and 46 microM for TdT, respectively. However, compound 1 did not influence the activities of plant DNA polymerases, human immunodeficiency virus type-1 reverse transcriptase, any of the prokaryotic DNA polymerases or DNA and RNA metabolic enzymes tested. Dose-dependent relationships were observed between the anti-inflammatory activities and the DNA polymerase-inhibitory activities of the four derivatives. The carboxylic acid moiety in the benzoic acid of the compounds appeared to be related to the inhibitory effects. The mode of action of the terpeno-benzoic acids against the polymerases and their relationships to the anti-inflammatory activity are discussed.


Hydrogen sulphide alleviates iron deficiency by promoting iron availability and plant hormone levels in Glycine max seedlings.
Hydrogen sulphide (H2S) is involved in regulating physiological processes in plants. We investigated how H2S ameliorates iron (Fe) deficiency in soybean (Glycine max L.) seedlings. Multidisciplinary approaches including physiological, biochemical and molecular, and transcriptome methods were used to investigate the H2S role in regulating Fe availability in soybean seedlings. Our results showed that H2S completely prevented leaf interveinal chlorosis and caused an increase in soybean seedling biomass under Fe deficiency conditions. Moreover, H2S decreased the amount of root-bound apoplastic Fe and increased the Fe content in leaves and roots by regulating the ferric-chelate reductase (FCR) activities and Fe homeostasis- and sulphur metabolism-related gene expression levels, thereby promoting photosynthesis in soybean seedlings. In addition, H2S changed the plant hormone concentrations by modulating plant hormone-related gene expression abundances in soybean seedlings grown in Fe-deficient solution. Furthermore, organic acid biosynthesis and related genes expression also played a vital role in modulating the H2S-mediated alleviation of Fe deficiency in soybean seedlings. Our results indicated that Fe deficiency was alleviated by H2S through enhancement of Fe acquisition and assimilation, thereby regulating plant hormones and organic acid synthesis in plants.


Khat: A Substance of Growing Abuse with Adverse Drug Interaction Risks.
The growing global availability of the stimulant shrub, khat, has aroused widespread concern. This paper is a review of possible adverse interactions between khat and conventional drugs. Khat chewing has been shown to reduce the bioavailabilities of orally co-administered antibiotics, ampicillin, amoxicillin, cephradine and tetracyclineHCl, and the antimalarial drug, chloroquine. The cardiovascular and central nervous system (CNS) stimulant effects of monoamine oxidase inhibitors (MAOI) and amphetamine-like drugs have been described to be enhanced by khat chewing. Khat is recognized to have the ability to counteract the effects of antihypertensive, antiarrhythmic and local anesthetic drugs, and to offset the cardioprotective action of aspirin. Depending on the amount or duration of consumption, khat has been reported to variably affect the actions of general anesthetics. Khat is likely to augment the effects and/or toxicity of different drugs due to its inhibitory action on the drug metabolizing enzyme CYP2D6. While specific mechanisms have been suggested for some of the khat-drug interactions reported, the mechanisms for other interactions are less clear. Despite the above observations, the literature reviewed is associated with a number of shortcomings, suggesting the need for further research and documentation on this area of knowledge. It is recommended that, in the interim, health care providers should be more familiar with the known and suspected adverse khat-drug interactions in order to optimally serve their patients who chew khat.


Longitudinal Evaluation of the Histological Changes in a Rat Model of Paravertebral Muscle Injury.
Thus far, few reports have described the time series histological variations in injured paravertebral muscle tissues for long durations, considering the type of pain. The purpose of this study is to evaluate histological changes in injured paravertebral muscles and dominant nerves considering the type of pain. We used 59 eight-week-old male Sprague-Dawley rats. A 115-g weight was dropped from a height of 1 m on the right paravertebral muscle. Fluoro-Gold (FG), a sensory nerve tracer, was injected into this muscle. Hematoxylin and eosin (HE) staining and nerve growth factor (NGF) immunostaining of the muscle were performed for histological evaluation. L2 dorsal root ganglia (DRG) on both sides were resected, and immunohistochemical staining was performed for calcitonin gene-related peptide (CGRP, a pain-related neuropeptide) and for activating transcription factor 3 (ATF3, a neuron injury marker). Each examination was performed at 3 days, 1-3 weeks, and 6 weeks after injury. HE staining of the paravertebral muscle indicated infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side at 3 days and 1 week after the injury. Fibroblasts and adipocytes were present at 2-3 weeks. At 6 weeks, the injured tissue was almost completely repaired. NGF was detected at 2-3 weeks post injury and appeared to colocalize with fibroblasts, but was not observed at 6 weeks post injury. The percentage of cells double-labeled with FG and CGRP in FG-positive cells of the primary muscle was significantly higher in the injured side at 3 days and 1-3 weeks post injury (P < 0.05). However, at 6 weeks, no significant difference was observed. No significant expression of ATF3 was observed. These results suggest that sensitization of the dominant nerve in the DRG, in which NGF may play an important role, can protract pain in injured muscles.


Free-standing health care facilities: financial arrangements, quality assurance and a pilot study.
Free-standing health care facilities now deliver many diagnostic and therapeutic services formerly provided only in hospitals. The financial arrangements available to these facilities differ according to whether the services are uninsured or insured. For an uninsured service, such as cosmetic surgery, the patient pays a fee directly to the service provider. For an insured service, such as cataract surgery, the provincial government uses tax revenues to fund the facility by paying it a facility fee and remunerates the physician who provided the service with a professional fee. No comprehensive, proactive quality assurance efforts have been implemented for either these facilities or the clinical practice provided within them. A pilot study involving therapeutic facilities in Ontario has suggested that a large-scale quality improvement effort could be undertaken in these facilities and rigorously evaluated.


Breaking the cycles of poverty: Strategies, achievements, and lessons learned in Los Cuatro Santos, Nicaragua, 1990-2014.
In a post-war frontier area in north-western Nicaragua that was severely hit by Hurricane Mitch in 1998, local stakeholders embarked on and facilitated multi-dimensional development initiatives to break the cycles of poverty. The aim of this paper is to describe the process of priority-setting, and the strategies, guiding principles, activities, achievements, and lessons learned in these local development efforts from 1990 to 2014 in the Cuatro Santos area, Nicaragua. Data were derived from project records and a Health and Demographic Surveillance System that was initiated in 2004. The area had 25,893 inhabitants living in 5,966 households in 2014. A participatory process with local stakeholders and community representatives resulted in a long-term strategic plan. Guiding principles were local ownership, political reconciliation, consensus decision-making, social and gender equity, an environmental and public health perspective, and sustainability. Local data were used in workshops with communities to re-prioritise and formulate new goals. The interventions included water and sanitation, house construction, microcredits, environmental protection, school breakfasts, technical training, university scholarships, home gardening, breastfeeding promotion, and maternity waiting homes. During the last decade, the proportion of individuals living in poverty was reduced from 79 to 47%. Primary school enrolment increased from 70 to 98% after the start of the school breakfast program. Under-five mortality was around 50 per 1,000 live births in 1990 and again peaked after Hurricane Mitch and was approaching 20 per 1,000 in 2014. Several of the interventions have been scaled up as national programs. The lessons learned from the Cuatro Santos initiative underline the importance of a bottom-up approach and local ownership of the development process, the value of local data for monitoring and evaluation, and the need for multi-dimensional local interventions to break the cycles of poverty and gain better health and welfare.


A Multi-Institutional Analysis of Damage Control Laparotomy in Elderly Trauma Patients: Do Geriatric Trauma Protocols Matter?
Trauma centers are receiving increasing numbers of older trauma patients. There is a lack of literature on the outcomes for elderly trauma patients who undergo damage control laparotomy (DCL). We hypothesized that trauma centers with geriatric protocols would have better outcomes in elderly patients after DCL. A retrospective chart review of consecutive adult trauma patients with DCL at 8 level 1 trauma centers was conducted from 2012 to 2018. Patients aged 40 or older were included. Age ≥ 55 years was defined as elderly. Demographics, injury information, clinical outcomes, including mortality, and complications were recorded. Univariate and multivariate analyses were performed. A total of 379 patients with DCLs were identified with an average age of 54.8 ± 0.4 years with 39.3% (n = 149/379) of patients aged ≥ 55. Geriatric protocols or a consulting geriatric service was present at 37.5% (n = 3/8) of institutions. Age ≥ 55 was a significant risk factor for in-hospital mortality (OR 2, 95% CI 1.0-4.0, P = .04). Institutions without dedicated geriatric trauma protocols/services had higher overall in-hospital mortality on both univariate (57.9% vs 34.3%, P = .02) and multivariate analyses (OR 2.1, 95% CI 1.3-3.4, P < .001). Surgical management of older trauma patients remains a challenge. Geriatric protocols or dedicated services were found to be associated with improved outcomes. Future efforts should focus on standardizing the availability of these resources at trauma centers.


A Life-Course Study of Cognitive Reserve in Dementia--From Childhood to Old Age.
To test a life-course model of cognitive reserve in dementia and examine if school grades around age 10 years, formal educational attainment, and lifetime occupational complexity affect the risk of dementia in old age. 7,574 men and women from the Uppsala Birth Cohort Multigenerational Study were followed for 21 years. Information on school performance, formal education, and occupational attainment was collected prospectively from elementary school archives and population censuses. Dementia diagnosis was extracted from the two Swedish registers. Discrete-time Cox proportional hazard models were estimated. Dementia was diagnosed in 950 individuals (12.5%). Dementia risk was lower among individuals with higher childhood school grades (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.68 to 0.93) and was lower among individuals in data-complex occupations (HR: 0.77; 95% CI: 0.64 to 0.92). Professional/university education predicted lower risk of dementia in minimally adjusted models (HR: 0.74; 95% CI: 0.60 to 0.91), although the effect faded with adjustment for occupational complexity. Lowest risk was found in the group with both higher childhood school performance and high occupational complexity with data (HR: 0.61; 95% CI: 0.50 to 0.75). Importantly, high occupational complexity could not compensate for the effect of low childhood grades. In contrast, dementia risk was reduced in those with higher school grades, irrespective of occupational complexity. Higher childhood school performance is protective of dementia risk, particularly when preserved through complex work environments in adulthood, although it will remain protective even in the absence of later-life educational or occupational stimulation.


Treatment for lymphedema of the arm--the Casley-Smith method: a noninvasive method produces continued reduction.
This paper gives an outline of the Casley-Smith method for the treatment of lymphedema of the arm. It includes a brief summary of the development of manual techniques and the terminology applied to them. The four principles of this method are skin care, manual lymphatic drainage, compression in the form of bandaging and/or garments, and exercise. The massage techniques, especially where they differ from other schools, are described in some detail, as are the principles that apply in compression and maintenance of reduction in lymphedema. The results of this method have been analyzed both in Australia and in the United States and are discussed briefly. Mention is made of the benefits of the benzopyrones, which have been used for many years, when added to the above treatment. Both benzopyrones and exercise will produce a continued reduction after the treatment course. They are particularly useful in a less compliant patient. It is stressed that the effect of patient compliance, particularly after treatment, makes a great difference to the ongoing success of the regime. A comparison is drawn between the efficacy of various current treatments and their cost. This shows that this combined and conservative method of treatment should be considered before recourse to pumps or surgery. The latter seldom achieve the results of decongestive lymphatic drainage, and, in the long term, they are more expensive. Certain preventive measures may be indicated following, e.g., mastectomies. Prevention of the onset of lymphedema is of extreme importance. However, a return to as normal a lifestyle as possible by the patient is also essential. The earlier treatment begins after the onset of lymphedema, the better the prognosis for the patient. Lymphedema can and should be treated.


Increased Lamin B1 Levels Promote Cell Migration by Altering Perinuclear Actin Organization.
Cell migration requires reposition and reshaping of the cell nucleus. The nuclear lamina is highly important for migration of both primary and cancer cells. B-type lamins are important for proper migration of epicardial cells and neurons and increased lamin B to lamin A ratio accelerates cancer cell migration through confined spaces. Moreover, a positive association between lamin B1 levels and tumor formation and progression is found in various cancer types. Still, the molecular mechanism by which B-type lamins promote cell migration is not fully understood. To better understand this mechanism, we tested the effects of lamin B1 on perinuclear actin organization. Here we show that induction of melanoma cell migration leads to the formation of a cytosolic Linker of Nucleoskeleton and Cytoskeleton (LINC) complex-independent perinuclear actin rim, which has not been detected in migrating cells, yet. Significantly, increasing the levels of lamin B1 but not the levels of lamin A prevented perinuclear actin rim formation while accelerated the cellular migration rate. To interfere with the perinuclear actin rim, we generated a chimeric protein that is localized to the outer nuclear membrane and cleaves perinuclear actin filaments in a specific manner without disrupting other cytosolic actin filaments. Using this tool, we found that disruption of the perinuclear actin rim accelerated the cellular migration rate in a similar manner to lamin B1 over-expression. Taken together, our results suggest that increased lamin B1 levels can accelerate cell migration by inhibiting the association of the nuclear envelope with actin filaments that may reduce nuclear movement and deformability.


Mineralocorticoid effector mechanism in preeclampsia.
Mineralocorticoid effector mechanisms were evaluated in 29 patients with preeclampsia and in 25 uncomplicated pregnancies by measurement of plasma aldosterone, levels of mineralocorticoid receptor (MR) in mononuclear leucocytes, and subtraction potential difference (SPD; rectal minus oral values). Mean values for plasma aldosterone were not different between the two groups, but significant differences were observed for MR (preeclampsia, 81 +/- 44 receptors/cell; controls, 306 +/- 168) and SPD (preeclampsia, 65 +/- 7 mV; controls, 12 +/- 5 mV). In six cases we determined MR, plasma aldosterone, and SPD in patients with preeclampsia before and 3 months after delivery. MR were reduced before delivery (96 +/- 27 receptors/cell), and SPD increased (64 +/- 8 mV), with both parameters normalizing after delivery (MR, 242 +/- 79; SPD, 14.0 +/- 4 mV). Aldosterone levels returned to normal nonpregnant values after delivery. These data suggest an important role for abnormalities in mineralocorticoid effector mechanisms in the etiology of preeclampsia and could be an useful marker for diagnosis.


[Solitary circumscribed neuroma (palisaded encapsulated neuroma) of the oral mucosa].
The solitary circumscribed neuroma or "Palisaded Encapsulated Neuroma" is an infrequent benign tumor of the skin of adults, often localised on the face, around the orifices. The involvement of the oral mucosa or of the vermilion border of the lips is rare. In our 5 cases, a small painless and more or less protruding nodule had been present for years on the mucosa of the hard palate (50 year-old man, 43 year-old woman), the soft palate (63 year-old woman), the vermilion border of the lower lip (48 year-old woman), and the gingiva (26 year-old man). The non specific clinical aspect did not permit a correct diagnosis. Histologically, the solitary circumscribed neuroma is formed by a proliferation of Schwann cells arranged in interlacing bundles, featuring one or several well-limited nodules, sometimes surrounded by a thin capsule. At first sight, this aspect might sometimes mimic schwannoma or neurofibroma. The lesion is interspersed with a variable amount of axons. An association with neurofibromatosis or MEN syndrome type IIb has never been found. Even after incomplete excision the solitary circumscribed neuroma does not recur, a fact supporting a reactive rather than a neoplastic origin.


Impact of gene patents and licensing practices on access to genetic testing for hearing loss.
Genetic testing for heritable hearing loss involves a mix of patented and unpatented genes, mutations and testing methods. More than half of all hearing loss is linked to inherited mutations, and five genes are most commonly tested for in the United States. There are no patents on three of these genes, but Athena Diagnostics holds exclusive licenses to test for a common mutation in the GJB2 gene associated with about 50% of all cases as well as mutations in the MTRNR1 gene. This fragmented intellectual property landscape made hearing loss a useful case study to assess whether patent rights in genetic testing can proliferate or overlap, and whether it is possible to gather the rights necessary to perform testing. Testing for hearing loss is widely available, primarily from academic medical centers. Based on literature reviews and interviews with researchers, research on the genetics of hearing loss has generally not been impeded by patents. There is no consistent evidence of a premium in testing prices attributable to patent status. Athena Diagnostics has, however, used its intellectual property to discourage other providers from offering some tests. There is no definitive answer about the suitability of current patenting and licensing of commonly tested genes because of continuing legal uncertainty about the extent of enforcement of patent rights. Clinicians have also expressed concerns that multiplex tests will be difficult to develop because of overlapping intellectual property and conflict with Athena's sole provider business model.


Are clear boundaries a prerequisite for well-functioning collaboration in home health care? A mixed methods study.
The aim of this study was to examine whether professional collaboration in home health care is associated with clear boundaries between principals' areas of responsibility and the professions areas of responsibility, respectively. Data were derived from a web-based survey that was carried out in one county in the middle of Sweden during spring 2013. Participants were health professionals and managers from the county council and from all the municipalities in the county. Both structured and open-ended questions were utilised. A total of 421 individuals (90% women) answered the structured questions, and 91 individuals (22% of the 421) answered the open-ended questions. Quantitative data were analysed with descriptive statistics methods, tests of independence and of correlation strength. Qualitative data were analysed with content analysis. The results from the structured questions showed that well-functioning collaboration was associated with clear boundaries between principals in the county overall, and for respondents in two of three parts of the county. Association between clear boundaries between professions and well-functioning collaboration was found in the county overall among the municipality population. However, in one part of the county, we did not find any correlations between well-functioning collaboration and clear boundaries between professions or principals, with the exception of home help services. The analysis of the open questions gave similar results as the quantitative analysis, illustrated within three themes: The significance of concepts, trust and interdependence, and collaboration as a means for well-being. The results indicate that, recently after an organisational change, clear boundaries between the principals' areas of responsibility and professions' area of responsibility respectively are necessary for effective cooperation between professionals. If the organisation and professionals have previous positive experience of colocated activities, clear boundaries do not share the same importance.


Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats).
Spinal cord injury causes severe bone loss. We report osteoclast resorption with severe trabecular and cortical bone loss, decreased bone mineral apposition, and growth plate abnormalities in a rodent model of contusion spinal cord injury. These findings will help elucidate the mechanisms of osteoporosis following neurological trauma. Limited understanding of the mechanism(s) that underlie spinal cord injury (SCI)-induced bone loss has led to few treatment options. As SCI-induced osteoporosis carries significant morbidity and can worsen already profound disability, there is an urgency to advance knowledge regarding this pathophysiology. A clinically relevant contusion model of experimental spinal cord injury was used to generate severe lower thoracic SCI by weight-drop (10 g x 50 mm) in adolescent male Sprague-Dawley rats. Body weight and gender-matched naïve (no surgery) rats served as controls. Bone microarchitecture was determined by micro-computed tomographic imaging. Mature osteoclasts were identified by TRAP staining and bone apposition rate was determined by dynamic histomorphometry. At 10 days post-injury we detected a marked 48% decrease in trabecular bone and a 35% decrease in cortical bone at the distal femoral metaphysis by micro-CT. A 330% increase in the number of mature osteoclasts was detected at the growth plate in the injured animals that corresponded with cellular disorganization at the chondro-osseous junction. Appositional growth studies demonstrated decreased new bone formation with a mineralization defect indicative of osteoblast dysfunction. Contusion SCI results in a rapid bone loss that is the result of increased bone resorption and decreased bone formation.


Stretch-induced overproduction of fibronectin in mesangial cells is mediated by the activation of mitogen-activated protein kinase.
An excessive production of extracellular matrix (ECM) proteins in glomerular mesangial cells is considered to be responsible for the development of mesangial expansion seen in diabetic nephropathy. Mechanical stretch due to glomerular hypertension has been proposed as one of the factors leading to an increase in the production of ECM proteins in mesangial cells, but the precise mechanism of stretch-induced overproduction of ECM proteins has not been elucidated. Herein, we provide the evidence that mitogen-activated protein kinase (MAPK) may play a key role in the overproduction of fibronectin (FN) in mesangial cells exposed to mechanical stretch. MAPK, also termed extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), was activated by mechanical stretch in time- and intensity-dependent manners. Stretch-induced activation of ERK was inhibited by herbimycin A, a tyrosine kinase inhibitor, but not by GF109203X or calphostin C, the inhibitors of protein kinase C. Mechanical stretch also enhanced DNA-binding activity of AP-1, and this enhancement was inhibited by PD98059, an inhibitor of MAPK or ERK kinase (MEK). Furthermore, mechanical stretch stimulated the expression of FN mRNA followed by a significant increase in its protein accumulation. PD98059 could prevent stretch-induced increase in the expression of FN mRNA and protein. These results indicate that the activation of ERK may mediate the overproduction of ECM proteins in mesangial cells exposed to mechanical stretch, an in vitro model for glomerular hypertension seen in diabetes.