Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism.
The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is the preferred drug for Parkinson's disease, but long-term treatment results in the drug-induced dyskinesias and other side effects. This study was undertaken to examine whether melatonin could potentiate low dose L-DOPA effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental parkinsonism. Mice were treated with the parkinsonian neurotoxin, MPTP, and different doses of melatonin and low doses of L-DOPA. Behavior, striatal histology, and dopamine metabolism were evaluated on the 7th day. MPTP-induced striatal dopamine loss was not modified by melatonin administration (10-30 mg/kg; i.p. at 10-hr intervals, 6 times; or at 2-hr intervals, by day). However, low doses of L-DOPA (5 mg/kg, by oral gavage) administered alone or along with melatonin (10 mg/kg, i.p.) twice everyday for 2 days, 10 hr apart, after two doses of MPTP significantly attenuated striatal dopamine loss and provided improvements in both catalepsy and akinesia. Additionally, Golgi-impregnated striatal sections showed preservation of the medium spiny neurons, which have been damaged in MPTP-treated mouse. The results demonstrated that melatonin, but not L-DOPA, restored spine density and spine morphology of medium spiny neurons in the striatum and suggest that melatonin could be an ideal adjuvant to L-DOPA therapy in Parkinson's disease, and by the use of this neurohormone, it is possible to bring down the therapeutic doses of L-DOPA.


The long and complex road in the search for treatment for mental disorders: An analysis of the process in five groups of patients.
Seeking treatment for mental-health problems is a complex process, with different underlying motives in each stage. However, the entire process and these motives have hardly been investigated. This study aims to analyze the different stages of the help-seeking process and their underlying motives in five groups of patients with different mental disorders. In all, 156 patients seeking treatment in outpatient mental health clinics were individually interviewed: 71 had Obsessive-Compulsive Disorder (OCD), 21 had Agoraphobia (AGO), 18 had Major Depressive Disorder (MDD), 20 had Anorexia Nervosa (AN), and 22 had Cocaine Dependence (COC). The AGO and MDD patients delayed significantly less time in recognizing their mental health symptoms. Moreover, MDD patients disclosed their symptoms and searched for professional help faster than the other groups. The most relevant variables in the recognition of disorders were the loss of control over the symptoms, the interference produced by these symptoms, and their negative impact on the person's emotional state. The most frequent barriers to seeking treatment were related to minimizing the symptoms and fear of stigma. Finally, the most important motivator for seeking treatment was the awareness that minimizing the symptoms did not help to reduce them, lessen their interference, or make them disappear.


Impact of multidisciplinary radiologic-pathologic correlation conference for benign image-guided breast biopsies on discordance rates and patient outcomes in a community teaching hospital.
As the assessment for radiologic-pathologic concordance, particularly for benign image-guided breast biopsies, is crucial in the management of patients with imaging abnormalities, many health institutions now conduct multidisciplinary conferences to assess the imaging and pathology findings in patients who had image-guided needle biopsy. We aimed to identify the radiologic-pathologic discordance rates and changes in patient outcomes resulting from the implementation of radiologic-pathologic correlation conferences in a community teaching hospital. Twenty-two (5.6%) out of 393 cases presented were deemed discordant given that the imaging characteristics of the lesions were far too suspicious radiologically to correlate with the benign pathology. Six cases were recommended for further imaging (four had stable lesion on follow- up, one was lost to follow-up and one case eventually had surgical excision which showed atypia); 14 cases for repeat core needle/excisional biopsy (seven had surgical excision with benign histology, five did not have surgery but showed stable lesion on imaging, two were lost to follow-up); one case for close imaging follow-up (lesion ultimately disappeared); the remaining case for second opinion (no follow-up data). The rad-path correlation conference led to a higher level of patient care with significant change in practice across our hospital network.


Ecological validity of manual grasping movements in an everyday-like grocery shopping task.
In our earlier research, kinematic and kinetic parameters of grasping differed significantly when participants grasped the same object once in a traditional laboratory paradigm, and once as part of a captivating computer game. We attributed this finding to the fact that grasping movements in the laboratory were repetitive and meaningless, while those in the computer game were embedded in complex behavior and served a meaningful purpose. In that work, we argued that grasping in the computer game is more characteristic of everyday life behavior; however, this conclusion has been criticized on the grounds that a computer game is not a typical everyday activity. The present study therefore compares grasping in a traditional laboratory paradigm to that in an indisputably everyday context: grocery shopping. Thirty-three young adults executed externally triggered arm movements to grasp nondescript objects (laboratory task, L) and place them on a tablet, or they walked through a fictitious grocery store towards a shelf to grasp grocery products and placed them into a shopping basket (everyday-like task, E). Size, shape, weight and location of to-be-grasped objects were identical in both tasks. We found that of the analyzed 16 kinematic parameters, 13 differed significantly between tasks. Specifically, grip apertures were larger, movements were slower and grip-transport coupling was more variable in E compared to L. We conclude that kinematic differences between both persist even if task is more realistic than in our earlier research. Our findings are compatible with the notion that movement planning is less stringent in E than in L.


Testing conditional multivariate rank correlations: the effect of institutional quality on factors influencing competitiveness.
Joint distribution between two or more variables could be influenced by the outcome of a conditioning variable. In this paper, we propose a flexible Wald-type statistic to test for such influence. The test is based on a conditioned multivariate Kendall's tau nonparametric estimator. The asymptotic properties of the test statistic are established under different null hypotheses to be tested for, such as conditional independence or testing for constant conditional dependence. Two simulation studies are presented: The first shows that the estimator proposed and the bandwidth selection procedure perform well. The second presents different bivariate and multivariate models to check the size and power of the test and runs comparisons with previous proposals when appropriate. The results support the contention that the test is accurate even in complex situations and that its computational cost is low. As an empirical application, we study the dependence between some pillars of European Regional Competitiveness when conditioned on the quality of regional institutions. We find interesting results, such as weaker links between innovation and higher education in regions with lower institutional quality. The online version contains supplementary material available at 10.1007/s11749-022-00806-1.


Historical biogeography of the ancient lycophyte genus Selaginella: early adaptation to xeric habitats on Pangea.
The ancient and cosmopolitan lycophyte genus Selaginella has living representatives around the world, but their historical biogeography has not been assessed with modern methods. We estimated a time-calibrated phylogeny using DNA marker regions rbcL and ITS1-5.8S-ITS2 from 200 species. Node density analyses revealed that Selaginellaceae has significantly older median and mean node ages than other putative "ancient" families. We used statistical model comparison to assess different biogeographical models on our dated tree, and to estimate ancestral ranges. These revealed that Selaginella originated on Euramerica around 383 Ma in the Devonian period, while its peak diversification began with the formation of Pangea. The divergence of the two main species-rich Selaginella lineages occurred approximately 318 Ma on the supercontinent. The major divergences within these main lineages of Selaginella took place in the Late Permian and Early Triassic, along with lineages highly adapted for xeric habitats on Pangea.


Dental caries in fluorine exposure areas in China.
In this study, fluorine concentrations in drinking water and in urine of residents from a fluorine exposure area in China were tested. DMFT (average number of decayed, missing and filled teeth) of local residents in four age groups were also determined. The results of the study indicate that in fluorine exposure areas, there is a strictly positive correlation between fluorine content in urine and the fluorine content in drinking water. Effect of dental caries by high fluorine content drinking water is different for the different age groups. High fluorine content drinking water is more dangerous for 15-and 18-year-old groups than 5- and 12-year-old groups.


Ischemic myocardial injury in cultured heart cells: preliminary observations on morphology and beating activity.
An in vitro model of myocardial ischemia has been established with primary monolayer cultures of neonatal rat heart cells. Ischemic conditions were simulated in vitro by subjecting the heart cell cultures to various levels of oxygen and glucose deprivation. After the ischemic treatments, cultures of beating muscle (M) cells were evaluated for functional and morphological changes. The experimental protocol consisted of treatment with 20% or 0% O2 and 1000, 500 or 0 mg glucose per 1 of medium for 4, 12 or 24 hr. Control cultures were treated with 20% O2 and 1000 mg glucose. The morphological alterations induced by the deficiency of O2 and glucose in the medium were the formation of pseudopodia and cytoplasmic vacuoles; increased cytoplasmic granulation; and the formation of abnormal cell shapes, such as long, spindly shaped M cells. There was a time-dependent decrease in beating activity as the M cells were exposed to longer durations of ischemic conditions. However, if the cultures were replenished with complete medium (1000 mg glucose) and 20% O2, the cells regained their ability to beat.


Acetylcholinesterase activity in the normal and retino-deprived optic tectum of the quail. Light and electron microscopic histochemistry and biochemical determination.
Acetylcholinesterase localization has been studied by electron microscopic histochemistry in the quail optic tectum. Ultrastructural analysis reveals that the different neuronal types in the tectum possess the metabolic pathways for AChE synthesis to different degrees. From the site of synthesis in cell bodies the enzyme spreads towards areas of neuropil. In the neuropil of AChE-rich areas a balance seems to exist between enzyme stored in dendrites (and sometimes axon terminals) and enzyme released into the extracellular spaces. Precise identification of cholinergic synapses by means of AChE localization is in most cases impossible, due to extensive spread of the enzyme through the extracellular compartments of the neuropil. Unilateral ocular ablation causes disappearance of the stratum opticum and decrease in thickness of the superficial tectal layers in the contralateral optic tectum, but only minor modifications in AChE localization. This finding is in agreement with biochemical results which show equivalence of the relative concentration of AChE in the right and left optic tectum 1 or 2 months after ablation of the right eye. The experimental evidence suggests that cholinergic mechanisms are not related to the discharge of retinal afferents on receptive tectal neurons, but more likely to intrinsic neural circuits which might be involved in the modulation of tectal activity.


Uncovering the experiences of engaging in an inpatient occupation-based group program: The LifeSkills group.
Consumer engagement is an important element for developing and maintaining value-based healthcare standards. Occupation-based practice in the context of a group has been adopted by inpatient rehabilitation clinicians, but little research has explored if these groups are valuable and useful to patients. To explore the experiences of patients participating in an occupation-based group intervention for instrumental activities of daily living to understand its value and usefulness in an inpatient rehabilitation setting. Interpretive description guided the development of the study. Semi-structured interviews were completed with 15 participants of an occupation-based group, the LifeSkills group. Comparative analysis was used to analyse the data and develop themes. Five themes were reported by participants: choice and control, confidence through doing, a real-world connection, the power of the therapeutic relationship and the impact of the shared experience. In line with current rehabilitation literature, patient experiences around client-centredness, occupational engagement in a 'real-world' environment, and valued relationships can be facilitated through an occupation-based group. This study supports the implementation of valued-based healthcare in understanding patient perceptions of occupation-based interventions into rehabilitation; ensuring that the right intervention is being used at the right time for the right patient.


Dextran sulfate sodium upregulates MAPK signaling for the uptake and subsequent intracellular survival of Brucella abortus in murine macrophages.
Brucellosis is one of the major zoonoses worldwide that inflicts important health problems in animal and human. Here, we demonstrated that dextran sulfate sodium (DSS) significantly increased adhesion of Brucella (B.) abortus in murine macrophages compared to untreated cells. Even without infection, Brucella uptake into macrophages increased and F-actin reorganization was induced compared with untreated cells. Furthermore, DSS increased the phosphorylation of MAPKs (ERK1/2 and p38α) in Brucella-infected, DSS-treated cells compared with the control cells. Lastly, DSS markedly increased the intracellular survival of Brucella abortus in macrophages by up to 48 h. These results suggest that DSS enhanced the adhesion and phagocytosis of B. abortus into murine macrophages by stimulating the MAPK signaling proteins phospho-ERK1/2 and p38α and that DSS increased the intracellular survival of B. abortus by inhibiting colocalization of Brucella-containing vacuoles (BCVs) with the late endosome marker LAMP-1. This study emphasizes the enhancement of the phagocytic and intracellular modulatory effects of DSS, which may suppress the innate immune system and contribute to prolonged Brucella survival and chronic infection.


Factors contributing to employment patterns after liver transplantation.
Many liver transplant recipients return to work, but their patterns of employment are unclear. We examine patterns of employment 5 years after liver transplantation. First-time liver transplant recipients ages 18-60 years transplanted from 2002 to 2009 and surviving at least 5 years were identified in the United Network for Organ Sharing registry. Recipients' post-transplant employment status was classified as follows: (i) never employed; (ii) returned to work within 2 years and remained employed (continuous employment); (iii) returned to work within 2 years, but was subsequently unemployed (intermittent employment); or (iv) returned to work ≥3 years post-transplant (delayed employment). Of 28 306 liver recipients identified during the study period, 12 998 survived at least 5 years and contributed at least 1 follow-up of employment status. A minority of patients (4654; 36%) were never employed, while 3780 (29%) were continuously employed, 3027 (23%) were intermittently employed, and 1537 (12%) had delayed employment. In multivariable logistic regression analysis, predictors of intermittent and delayed employment included lower socioeconomic status, higher local unemployment rates, and post-transplant comorbidities or complications. Never, intermittent, and delayed employment are common after liver transplantation. Socioeconomic and labor market characteristics may add to clinical factors that limit liver transplant recipients' continuous employment.


Ocular toxoplasmosis: the role of retinal pigment epithelium migration in infection.
Our aim was to study the migration of retinal pigmented epithelium (RPE) into the retinal layer during infection of C57BL/6 mice with Toxoplasma gondii. Eyes from infected and non-infected animals were analyzed on the 60th day of infection by light and transmission electron microscopy. Non-infected eyes showed a normal morphology. In contrast, we observed free parasites in the retinal vasculature, the presence of mononuclear inflammatory infiltrate (MNII) and parasites in the vasculature of choroids in infected eyes. No inflammatory infiltrate was observed; RPE cells were identified near the MNII in nuclear and plexiforme layers. RPE cells were also found on the ganglion cell layer and in the outer segments of the photoreceptor. The morphology showed that RPE cells caused a discontinuity in the nuclear and plexiforme layers. Clusters of parasites were found surrounded by RPE cells and MNII in the inner plexiforme layers. Ultrastructural analysis showed that RPE cells migrated through the epithelium into the inner retinal layers. We did not observe Toxoplasma cysts in many eyes in which pathological changes were detected. Only 8.3% of the animals had Toxoplasma cysts in the inner nuclear layer in the absence of inflammatory cells. The migration of RPE cells can be triggered by a disruption of the RPE monolayer or injury to the neural retina, as in the case of toxoplasmosis.


Quantitative relationships among high-throughput sequencing, cyanobacteria toxigenic genotype abundance and microcystin occurrence in bathing waters.
Toxin-producing cyanobacteria pose significant threats to human and animal health if exposed during recreational activities in bathing waters. To better safeguard public health and reduce health risks during the bathing season, an effective monitoring and management strategy is required. Molecular tools used to monitor toxigenic cyanobacteria have been evaluated on the basis of the efficiency and applicability of the method used to (i) establish an early-warning monitoring strategy for EU bathing water sites using both targeted quantitative polymerase chain reaction (qPCR) and non-targeted high-throughput sequencing (HTS) genotype analysis and (ii) to compare the toxigenic potential of cyanobacteria with actual microcystin (MC) occurrence and concentrations. For this purpose, 16 bathing water sites were monitored according to the bathing water directive (BWD) of the European Union (EU) during the bathing season of the summer of 2020 in eastern Austria. The cyanobacterial community composition was analyzed through HTS and qPCR by targeting the microcystin synthetase B gene (mcyB), which indicates MC synthesis within the genera Microcystis and Planktothrix. Within the genus Microcystis, which was identified as the primary MC producer, the mcyB genotypes formed stable subpopulations that increased linearly in correlation with the total Microcystis population. Notably, the HTS cell equivalents assigned to Microcystis and Planktothrix correlated with the corresponding qPCR estimates of genotype abundance, which serves as a confirmation of the suitability of (semi)-quantitative sequencing through HTS. In addition to the elevated trophic state, reduced transparency, increasing water temperatures, as well as cyanobacterial HTS read numbers and Microcystis cell number equivalents per mL estimated through qPCR, were associated with positive MC samples. Therefore, in combination with the monitoring of standard environmental parameters, the use of HTS and qPCR techniques is considered highly useful to ensure the timely identification of health risks to recreational users, as mandated by the BWD.


Characterization of calcified deposits on contraceptive intrauterine devices.
The formation of calcified deposits on > 200 contraceptive intrauterine devices (IUD) was quantitated as a function of time in healthy women, pregnant women, and women with a pathologic lesion. The incrustment formation was significantly enhanced when inflammation occurred, but change could not be observed in cases of pregnancy. The incrustments were analyzed by x-ray diffraction, infrared spectroscopy, x-ray microprobe, and ultramicrochemical stone analysis techniques. Major components and their average w/w percent quantities in the incrustments are as follows: calcium carbonate 75%, apatite 5%, and organic matrix 20%. Earlier hypotheses on the chemical processes of deposit formation are discussed, and a new, ionic mechanism of calcification on IUD surfaces is suggested.


A "TNM" classification system for cancer pain: the Edmonton Classification System for Cancer Pain (ECS-CP).
The purpose of this paper is to provide an overview of the development of a "TNM" cancer pain classification system for advanced cancer patients, the Edmonton Classification System for Cancer Pain (ECS-CP). Until we have a common international language to discuss cancer pain, understanding differences in clinical and research experience in opioid rotation and use remains problematic. The complexity of the cancer pain experience presents unique challenges for the classification of pain. To date, no universally accepted pain classification measure can accurately predict the complexity of pain management, particularly for patients with cancer pain that is difficult to treat. In response to this gap in clinical assessment, the Edmonton Staging System (ESS), a classification system for cancer pain, was developed. Difficulties in definitions and interpretation of some aspects of the ESS restricted acceptance and widespread use. Construct, inter-rater reliability, and predictive validity evidence have contributed to the development of the ECS-CP. The five features of the ECS-CP--Pain Mechanism, Incident Pain, Psychological Distress, Addictive Behavior and Cognitive Function--have demonstrated value in predicting pain management complexity. The development of a standardized classification system that is comprehensive, prognostic and simple to use could provide a common language for clinical management and research of cancer pain. An international study to assess the inter-rater reliability and predictive value of the ECS-CP is currently in progress.


Association between the CLOCK gene polymorphism and depressive symptom mediated by sleep quality among non-clinical Chinese Han population.
Depression is a common mental disorder associated with sleep problems and the circadian clock genes may underlie the relationship between the two in clinical samples. However, little is known about whether poor sleep quality is associated with depressive symptom in healthy individuals and whether is mediated by specific single-nucleotide polymorphisms (SNPs). Using a cross-sectional design, 444 university staff members were randomly recruited in Beijing. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality, the Zung's Self-rating Depression Scale (SDS) to measure depressive symptom, and the Work Stress Scale to measure job stress. The CLOCK gene rs12649507 polymorphism was genotyped in 289 blood samples. There were positive inter-correlations between job stress, PSQI and SDS (almost ps < 0.05). GG homozygotes of the SNP had higher PSQI and its sleep duration and daytime dysfunction scores than AA homozygotes (all Bonferroni corrected ps0.05). The SNP had no main effect on the SDS and did not interact with job stress to affect SDS, PSQI and its dimensions (all ps > 0.05). Interestingly, after controlling for job stress and covariates, the significant effect size of the SNP on the SDS mediated by the PSQI was 0.68 (95% CI [0.24, 1.35]). Some limitations included single professional background, cross-sectional study design, small sample size and potential confounding factors, which could be amended by future research. Non-clinical Chinese carrying CLOCK gene rs12649507 G-allele may lead to poor sleep quality and further depression symptoms.


Actions of vasoactive intestinal polypeptide in superior cervical ganglion of the cat.
Effects of vasoactive intestinal polypeptide (VIP) in the superior cervical ganglion (SCG) of the cat were investigated in situ. Vasoactive intestinal polypeptide (0.075-1.5 nmol) induced a dose-dependent depolarization of the superior cervical ganglion, characterized by a long-latency, slow onset, small amplitude and long duration. Initial short-lasting hyperpolarization of the superior cervical ganglion was observed in 5 out of 8 experiments after administration of VIP in a dose of 0.75 nmol. Vasoactive intestinal polypeptide (0.075-1.5 nmol) unmasked the muscarinic slow negative potential, following the compound action potential and unmasked or enhanced the stimulus-bound decremental oscillatory potentials induced by the muscarinic agonist McN-A-343 in the superior cervical ganglion. Vasoactive intestinal peptide induced a slight, but significant increase in the amplitude of the postganglionic action potentials evoked by preganglionic stimulation. The data mentioned above suggest that VIP may act as a neuromodulator of cholinergic transmission at the ganglionic synapse.


Donor brain death significantly interferes with tolerance induction protocols.
Studies in rodents showed that antibodies are able to induce tolerance of allografts. As clinical results are unsatisfactory and deceased donors are still the main source of organ transplants, we investigated whether donor brain-death impacts on tolerance induction after experimental kidney transplantation. Anti-CD4 monoclonal antibodies (RIB 5/2; 2.5 mg/kg x 5 days) treated and untreated recipients of brain-dead donor grafts were compared with RIB 5/2 treated and untreated recipients of living donor grafts (F344-to-Lewis). All recipients received low-dose CsA (1.5 mg/kg x 10 days). Kidneys were recovered 4, 16 and 40 weeks after transplantation and examined by morphology, immunohistology and flow cytometry. Renal function was monitored monthly. RIB 5/2 treatment significantly decreased proteinuria in recipients of living donor allografts when compared with living donor controls. After 40 weeks, inflammatory cell infiltration and MHC class II expression were reduced while morphologic alterations were minimal. In contrast, treatment of brain-dead graft recipients had no impact on graft function. Structural changes and graft infiltration were comparable to brain-dead donor controls at all time points. RIB 5/2 treatment significantly improved graft function in recipients of living donor grafts; however, it was not effective in recipients of brain-dead donor organs.


A unique approach to evaluation of emergency care.
A quality care evaluation system was designed to serve as a framework for on-going research in the area of quality assurance in emergency medicine. It included a set of basic evaluation tools, such as direct observation of patient care, record review and analysis, and patient follow-up interview for outcome. These tools are used in an attempt to quantify relationships between quality care and patient outcome.


[A measurement and computing complex for control of the state of the operator].
Herein is described the structure and technical parameters of the computer aided complex for the control of changes in operator's state. The design of the specialised operating system and software attached are considered. The article is quite interesting for the specialists engaged in the field of computer aided complex units, for the functional diagnostic specialists and specialists involved in automation of medical research work.


Large Language Models in Ophthalmology Scientific Writing: Ethical Considerations Blurred Lines or Not at All?
To discuss the implications of large language models (LLMs) in ophthalmology research, as well as the associated ethical considerations. Perspective. This discussion reviews the potential uses of LLMs such as ChatGPT in ophthalmology research, highlights the associated threats and ethical considerations, and proposes solutions for the use of LLMs in ophthalmology research and scientific writing. With the increasing interest in LLMs, such as ChatGPT, their diverse utility has been widely explored, including their application in research and scientific writing. LLMs have the potential to guide researchers throughout the different stages of their research, from idea generation to drafting a scientific piece. However, there are significant ethical concerns and challenges related to scientific integrity in ophthalmology research that should be addressed by scientific journals. Our review of the 10 highest-impact-factor ophthalmology journals revealed that the number of journals addressing this topic in their submission guidelines is rapidly increasing. Therefore, we propose certain domains that all journals should consider regarding the use of LLMs in research. As LLMs continue to improve, their use in scientific writing will remain a contentious issue due to the ethical dilemmas involved in determining the appropriate scope of their use. This article reviews the ethical dilemmas related to the use of LLMs in ophthalmology research and calls for the prompt development of guidelines for their ethical use in manuscript writing as ophthalmology journals update their editorial policies with respect to LLMs.


Phylogenic analysis of adhesion related genes Mad1 revealed a positive selection for the evolution of trapping devices of nematode-trapping fungi.
Adhesions, the major components of the extracellular fibrillar polymers which accumulate on the outer surface of adhesive traps of nematode-trapping fungi, are thought to have played important roles during the evolution of trapping devices. Phylogenetic analyses based on the genes related to adhesive materials can be of great importance for understanding the evolution of trapping devices. Recently, AoMad1, one homologous gene of the entomopathogenic fungus Metarhizium anisopliae cell wall protein MAD1, has been functionally characterized as involved in the production of adhesions in the nematode-trapping fungus Arthrobotrys oligospora. In this study, we cloned Mad1 homologous genes from nematode-trapping fungi with various trapping devices. Phylogenetic analyses suggested that species which formed nonadhesive constricting ring (CR) traps more basally placed and species with adhesive traps evolved along two lineages. Likelihood ratio tests (LRT) revealed that significant positive selective pressure likely acted on the ancestral trapping devices including both adhesive and mechanical traps, indicating that the Mad1 genes likely played important roles during the evolution of nematode-trapping fungi. Our study provides new insights into the evolution of trapping devices of nematode-trapping fungi and also contributes to understanding the importance of adhesions during the evolution of nematode-trapping fungi.


Method for calculating optical coating stabilities.
The reflectivity R of a multilayer stack and its first and second derivatives with respect to the phase change are derived here by a recursive method. These equations improve the determination of stability conditions for coatings and widen the applications to treatments other than antireflection coatings, as reported by Mouchart [Appl. Opt. 16, 2486 (1977)]. Some calculations are performed on grazing incidence antireflection coatings, all-dielectric mirrors, and bandpass filters with non-quarter-wave layers.


Thyroid hormones inhibit platelet function and myosin light chain kinase.
We examined the extranuclear effects of thyroid hormones on human platelets. Pretreatment with DL-thyroxine or DL-triiodothyronine inhibited collagen-induced aggregation, in a dose-dependent manner, but other derivatives of thyroid hormone had no significant effects. In contrast to collagen, 12-O-tetradecanoylphorbol-13-acetate-induced aggregation was not affected by thyroid hormones at the same concentration range. Thyroxine also inhibited the release of [14C] serotonin from collagen-stimulated platelets, with a marked reduction in the phosphorylation of 20,000-dalton protein. Thyroxine and triiodothyronine had inhibitory effects on myosin light chain kinase purified from human platelets and inhibited more markedly the myosin light chain kinase than protein kinase C (Ca2+/phospholipid-dependent enzyme) and cAMP-dependent protein kinase. In addition, L-thyroxine behaved as a competitive inhibitor of myosin light chain kinase toward calmodulin, and the Ki value was calculated to be 2.6 microM. To determine whether or not thyroxine directly binds myosin light chain kinase, we prepared an affinity column, using L-thyroxine as the ligand. Myosin light chain kinase was selectively bound to the column while calmodulin passed through. We also designed a procedure for the purification of myosin light chain kinase from human platelets, using L-thyroxine-affinity chromatography. A markedly increased purification was thus achieved, and DEAE-cellulose and L-thyroxine-affinity chromatography were made feasible. These results suggest that thyroxine can serve as a pharmacological tool for elucidating the biological significance of myosin light chain kinase-mediated reactions and is a pertinent ligand which can be used to purify myosin light chain kinase from platelets as a substitute for calmodulin.


Direction perception in complex dynamic displays: the integration of direction information.
We created random-dot cinematograms in which each dot's successive movements were independently drawn from a Gaussian distribution of directions of some characteristic bandwidth. Such a display, comprising many different, spatially intermingled local motion vectors, can produce a percept of global coherent motion in a single direction. Using pairs of cinematograms, direction discrimination of global motion was measured under various conditions of direction distribution bandwidth, exposure duration, and constancy of each dot's path. A line-element model gave an excellent account of the results: (i) over a considerable range, discrimination was unaffected by the cinematogram's direction distribution bandwidth; (ii) only for the briefest presentations did changes in duration have an effect; (iii) so long as the overall directional content of the cinematogram remained unchanged, the constancy or randomness of individual dots' paths did not affect discrimination. Finally, the line-element model continued to give a good account of the results when we made additional measurements with uniform rather than Gaussian distributions of directions.


Keverprazan, a novel potassium-competitive acid blocker: Multiple oral doses safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy subjects.
Keverprazan, a novel potassium-competitive acid blocker, was approved for treating acid-related diseases. This study aimed to analyze the safety, pharmacokinetics (PKs) and pharmacodynamics (PDs) of multiple doses of keverprazan. This was a randomized, positive-/placebo-controlled, phase Ic trial. Twenty-six healthy adults were randomized to receive 20 mg/day keverprazan (n = 8), 40 mg/day keverprazan (n = 8), placebo (n = 6), or 20 mg/day vonoprazan (n = 4) for 7 days. Safety, PK and PD assessments were conducted. In the keverprazan, vonoprazan, and placebo groups, adverse events (AEs) were reported in nine (56.25%), two (50.00%), and three (50.00%) subjects, respectively. AEs were mild except a moderate abdominal pain leading to withdraw. No serious AEs occurred. The plasma concentration-time profiles of keverprazan showed rapid absorption (median time to maximum plasma concentration of 1.25-3.0 h). The terminal half-life was 6.23 and 7.01 h for keverprazan 20 and 40 mg groups on day 7. The maximum plasma concentration was 43.1 and 93.2 ng/mL, respectively. There was no apparent accumulation of keverprazan and the major metabolite after 7-day administration. The intragastric pH greater than 5 holding time ratios (HTRs) over 24 h postdose increased from 79.1%, 84.4%, and 84.5% on day 1 to 99.0%, 97.4%, and 100.0% on day 7 in the vonoprazan 20 mg and keverprazan 20 and 40 mg groups, respectively. The intragastric pH greater than 5 HTR of keverprazan reached a plateau at 20 mg. Keverprazan is well-tolerable. A steady-state in exposure was generally reached after 7 days of treatment. A dose of 20 mg/day keverprazan can elicit a significant, stable, and long-lasting gastric acid inhibition effect.


Advanced practice nurses and evidence-based practice. An opportunity for change.
In a context of aging of the population, increased prevalence of chronic diseases and increasing complexity, it is necessary to define new professional roles that can meet the health needs of the population. Added to this is the certainty that variability in clinical practice, as well as in health management, makes it necessary to use best evidence as the basis for decision-making. But the application of clinical practice based on evidence in a specific context implies a broad mastery of the available evidence, its applicability and limitations, as well as a deep understanding of the particular characteristics of the area where it is to be applied, from the "macro" (health policies, framework regulations, strategic lines, social values, etc.) to the "micro" level (local culture, user preferences, etc.). The "Health Service of the Balearic Islands", in collaboration with the Faculty of Nursing and Physiotherapy from the University of the Balearic Islands, proposes the development of new advanced practice nursing roles that focus their efforts on the planned implementation of evidence in clinical settings. Advanced practice nurses have managed naturally, thanks to their competence development, to exercise the role of promoting organizational and attitudinal changes that facilitate the implementation of evidence in organizations and complex environments.


Serum neurofilament light chain correlates with myelin and axonal magnetic resonance imaging markers in multiple sclerosis.
Neurofilaments are cytoskeletal proteins that are detectable in the blood after neuroaxonal injury. Multiple sclerosis (MS) disease progression, greater lesion volume, and brain atrophy are associated with higher levels of serum neurofilament light chain (NfL), but few studies have examined the relationship between NfL and advanced magnetic resonance imaging (MRI) measures related to myelin and axons. We assessed the relationship between serum NfL and brain MRI measures in a diverse group of MS participants. 103 participants (20 clinically isolated syndrome, 33 relapsing-remitting, 30 secondary progressive, 20 primary progressive) underwent 3T MRI to obtain myelin water fraction (MWF), geometric mean T2 (GMT2), water content, T1; high angular resolution diffusion imaging (HARDI)-derived axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA); diffusion basis spectrum imaging (DBSI)-derived AD, RD, FA; restricted, hindered, water and fiber fractions; and volume measurements of normalized brain, lesion, thalamic, deep gray matter (GM), and cortical thickness. Multiple linear regressions assessed the strength of association between serum NfL (dependent variable) and each MRI measure in whole brain (WB), normal appearing white matter (NAWM) and T2 lesions (independent variables), while controlling for age, expanded disability status scale, and disease duration. Serum NfL levels were significantly associated with metrics of axonal damage (FA: R2WB-HARDI = 0.29, R2NAWM-HARDI = 0.31, R2NAWM-DBSI = 0.30, R2Lesion-DBSI = 0.31; AD: R2WB-HARDI=0.31), myelin damage (MWF: R2WB = 0.29, R2NAWM = 0.30, RD: R2WB-HARDI = 0.32, R2NAWM-HARDI = 0.34, R2Lesion-DBSI = 0.30), edema and inflammation (T1: R2Lesion = 0.32; GMT2: R2WB = 0.31, R2Lesion = 0.31), and cellularity (restricted fraction R2WB = 0.30, R2NAWM = 0.32) across the entire MS cohort. Higher serum NfL levels were associated with significantly higher T2 lesion volume (R2 = 0.35), lower brain structure volumes (thalamus R2 = 0.31; deep GM R2 = 0.33; normalized brain R2 = 0.31), and smaller cortical thickness R2 = 0.31). The association between NfL and myelin MRI markers suggest that elevated serum NfL is a useful biomarker that reflects not only acute axonal damage, but also damage to myelin and inflammation, likely due to the known synergistic myelin-axon coupling relationship.


Silver nanoparticles potentiate antitumor and oxidant actions of cisplatin via the stimulation of TRPM2 channel in glioblastoma tumor cells.
We investigated the effects of silver nanoparticle (AgNP) and cisplatin (CiSP) exposure via the activation of TRPM2 cation channels in glioblastoma (DBTRG-05MG) cell line. The cells were divided into four groups as control, AgNPs (100 μg/ml for 48 h), CiSP (25 μM for 24 h), and CiSP + AgNPs. We found that the cytotoxic, oxidant and apoptotic actions of CiSP were further stimulated through the activation of TRPM2 (via ADP-ribose and H2O2) in the cells by the treatment of AgNPs. The actions were decreased in the cells by the treatments of TRPM2 antagonists (ACA and 2APB). The apoptotic actions of AgNPs were induced by the stimulation of propidium iodide positive DBTRG-05MG rate, caspase -3, caspase -8, and caspase -9 activations, although their oxidant actions were acted by the increase of mitochondrial membrane depolarization, lipid peroxidation, mitochondrial oxygen free radicals (ROS), and cytosolic ROS, but the decrease of total antioxidant status, glutathione, and glutathione peroxidase. The accumulation of cytosolic free Ca2+ and Zn2+ into mitochondria via the activation of TRPM2 current density and activity accelerated oxidant and apoptotic actions of AgNPs in the cells. We found that the combination of AgNPs and CiSP was synergistic via the stimulation of TRPM2 for treatment of DBTRG-05MG cells. The combination of AgNPs and CiSP showed a favorable action via the stimulation of TRPM2 in the treatment of glioblastoma tumor cells.


Role of WNT1-inducible-signaling pathway protein 1 in etoposide resistance in lung adenocarcinoma A549 cells.
The aim of this study was to explore the role of WNT1-inducible-signaling Pathway Protein 1 (WISP-1) in etoposide resistance in lung adenocarcinoma A549 cells. WISP-1 overexpression A549 lung adenocarcinoma cell was established. After exposure to ultraviolet (UV) and etoposide, cell viability and apoptosis were evaluated. Moreover, western-blot was employed to examine the expression of apoptotic pathway proteins. In addition, a nude mice tumor model was established to examine the effect of WISP-1 overexpression in vivo and TUNEL staining was used to assess cell apoptosis of tumor tissue. WISP-1 overexpression significantly increased cell viability and decreased cell apoptosis after treatment with UV and etoposide. Decreased expression of Bad and Bax and increased expression of Bcl-2 was found after etoposide treatment in WISP-1 overexpressed cells. A significantly increasing of tumor volume in WISP-1 overexpressed group was found and TUNEL staining revealed that decreased cell apoptosis in WISP-1 overexpressed group. Our results demonstrated that WISP-1 may have a facilitating role in etoposide resistance through increasing cell viability and decreasing cell apoptosis.


Transfer RNAs for primordial amino acids contain remnants of a primitive code at position 3 to 5.
Analysis of the nucleotide sequence of 1,400 transfer RNAs has revealed the imprint of a prototypic genetic code in position 3-4-5 of the acceptor stem. It appears only in the transfer RNAs for the primordial amino acids ie those found by chemical condensation of a nitrogen-methane-water-ammonia mixture. The model for primitive protein synthesis as mentioned by Crick assumes a direct interaction between the amino acid and a prototypic adaptor oligonucleotide. This has hitherto appeared irreconcilable with the large spatial separation between the aminoacylation site and the anticodon in present day transfer RNAs. The observations reported here show how this paradox can be resolved by a process of duplication and cleavage of a prototypic adaptor.


Neural release of substance P causes dilation of arterioles in rat striated muscle.
Substance P, which is present in small nerve terminals and proximal to microvessels in rat strated muscle, may have a vasodilator role if released into the microcirculation. Male, Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and the cremaster muscle, with intact blood supply and innervation, was suspended in a bath containing a physiological salt solution. The major autonomic innervation to the cremaster (genito-femoral nerve) was isolated and its cut, distal end was stimulated (3-5 Hz, 2 ms, 10-20 V). Diameters of third order arterioles (14-23 microns) were measured by television microscopy. Stimulation after a 20-min pretreatment with the alpha-adrenergic receptor antagonist phentolamine (2.10(-5) M) unmasked a moderate vasodilation, which was attenuated by treatment with the substance P receptor antagonist [D-Arg1,D-Pro2, D-Trp7,9,Leu11]-substance P (1.10(-6) M). This neurogenic vasodilation was not sensitive to muscarinic receptor blockade by atropine (1.10(-4) M), but was partially blocked by the beta-adrenergic receptor antagonist propranolol (1.10(-5) M). These data suggest that the rat striated muscle microvasculature is innervated with nerves containing substance P, and the release of substance P from the nerve terminals causes arteriolar dilation.


[Systematic assessment of the paediatrician's performance during simulated supraventricular tachycardia].
The aims of this study are to: a) assess the quality in clinical management during a simulated scenario of acute supraventricular tachycardia (SVT) by means of a structured task-based checklist and to b) detect pitfalls and grey areas where reinforcement in training may be needed. We systematically reviewed SVT simulated scenarios during simulation courses between June 2008 and April 2010. Three scenarios were programmed using SimBaby® simulation system, and included stable SVT (S-SVT), stable progressing to unstable SVT (SU-SVT) and unstable SVT (U-SVT). Scenarios were evaluated by means of an 18-task checklist based on ILCOR international recommendations. A total of 45 scenarios were assessed with the participation of 167 paediatricians, including 15 S-SVT, 25 SU-SVT and 5 U-SVT scenarios. Out of a total of 551 possible tasks, 328 (59.5%) were completed correctly. The mean percentage of correct tasks per scenario was 63.4 (16.7) for S-SVT, 47.8 (20.3) for SU-ST and 38.6 (31) for U-SVT (p=0.028). There were no significant differences between primary care paediatricians and hospital paediatricians. Most of the participants correctly identified non-sinus rhythm as SVT. However, important pitfalls were observed, including failure to identify haemodynamic instability in 20 out of 43 (48%) cases, an incorrect dose of adenosine in 18 out of 39 (48%), incorrect adenosine administration in 23 out of 39 (59%), and non-recognition of indication to emergent cardioversion in 15 out of 31 (48%). Paediatricians are able to diagnose SVT correctly, but need to improve their skills in treatment. Systematic analysis of clinical performance in a simulated scenario allows the identification of strengths, as well as weak points, where reinforcement is needed.


Fatality of Staphylococcus aureus infections in a Greek university hospital: role of inappropriate empiric treatment, methicillin resistance, and toxin genes' presence.
The aim of the present study was to identify predictors of fatality among patients with S. aureus infections requiring hospitalization. Cases hospitalized with S. aureus infections at the University General Hospital of Patras, Greece, during a 4-year period (2013-2016) were studied. mecA, lukS/lukF-PV (Panton-Valentine leukocidin, PVL), tst (toxic shock syndrome toxin), fnbA (fibronectin-binding protein A), eta, and etb (epidermolytic toxins) genes' carriage was detected by PCR in 149 selected patients. Among 464 patients, 346 were included (118 with missing data). Primary bacteremia predominated (44.2%), followed by lower respiratory tract infections (13.6%), deep seated infections (9.8%), osteoarticular (9.5%), and catheter-related bloodstream infections (6.1%). Methicillin-resistant S. aureus (MRSA) represented 33.8% of infections and were less likely to receive appropriate empiric treatment (79.5% versus 97.4%; P < 0.001). Thirty-day fatality was 14.5%. Multivariate analysis revealed that development of septic shock, Charlson Comorbidity Index, lower respiratory tract infection, bacteremia (primary or secondary), MRSA, and CRP was significantly associated with fatality. Appropriate empiric treatment was a predictor of good prognosis. Thirty-two out of 149 S. aureus (21.5%) carried lukS/lukF-PV genes, whereas, 14 (9.4%), 133 (78.7%), four (2.7%), and one (0.7%) carried tst, fnbA, eta, and etb genes, respectively. No difference was found among toxin genes' presence and mortality. PVL was significantly more frequently found among MRSA as compared to MSSA (45.1% versus 9.2%; P < 0.001). MRSA represented one third of the infections requiring hospitalization and were independently associated with fatality, probably since were more likely to receive inappropriate antibiotic treatment as compared to MSSA.


Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis.
Pain in knee osteoarthritis (OA) has historically been attributed to peripheral pathophysiology; however, the poor correspondence between objective measures of disease severity and clinical symptoms suggests that non-local factors, such as altered central processing of painful stimuli, also contribute to clinical pain in knee OA. Consistent with this notion, recent evidence demonstrates that patients with knee OA exhibit increased sensitivity to painful stimuli at body sites unaffected by clinical pain. In order to further investigate the contribution of altered pain processing to knee OA pain, the current study tested the hypothesis that symptomatic knee OA is associated with enhanced sensitivity to experimental pain stimuli at the knee and at remote body sites unaffected by clinical pain. We further anticipated that pain sensitivity would differ as a function of the OA symptom severity. Older adults with and without symptomatic knee OA completed a series of experimental pain assessments. A median split of the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) was used to stratify participants into low vs high OA symptom severity. Compared to controls and the low symptom group, individuals in the high symptom group were more sensitive to suprathreshold heat stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in the low symptomatic OA group subgroup exhibited experimental pain responses similar to the pain-free group on most measures. No group differences in endogenous pain inhibition emerged. These findings suggest that altered central processing of pain is particularly characteristic of individuals with moderate to severe symptomatic knee OA.


Mood stabilizers and anticonvulsants.
This article provides pediatricians and other clinicians who treat children and adolescents with a working knowledge of mood stabilizers and their potential uses in children and adolescents with mood and behavior disorders. Mood stabilizers are ubiquitous agents that are often effective in the treatment of children and adolescents with bipolar disorders or conduct disorders and mentally retarded patients with aggressive behavior. The authors' also discuss mechanisms of action, pharmacokinetics, dosing, drug interactions, and potential uses. Following these medication details, specific information concerning the diagnosis and treatment of several child and adolescent mood and behavior disorders, and in which treatment with mood stabilizers may be helpful, is presented.


Engineering Brain-Specific Pericytes from Human Pluripotent Stem Cells.
Pericytes (PCs) are a type of perivascular cells that surround endothelial cells of small blood vessels. In the brain, PCs show heterogeneity depending on their position within the vasculature. As a result, PC interactions with surrounding endothelial cells, astrocytes, and neuron cells play a key role in a wide array of neurovascular functions such as regulating blood-brain barrier (BBB) permeability, cerebral blood flow, and helping to facilitate the clearance of toxic cellular molecules. Therefore, a reliable method of engineering brain-specific PCs from human induced pluripotent stem cells (hiPSCs) is critical in neurodegenerative disease modeling. This review summarizes brain-specific PC differentiation of hiPSCs through mesoderm and neural crest induction. Key signaling pathways (platelet-derived growth factor-B [PDGF-B], transforming growth factor [TGF]-β, and Notch signaling) regulating PC function, PC interactions with adjacent cells, and PC differentiation from hiPSCs are also discussed. Specifically, PDGF-BB-platelet-derived growth factor receptor β signaling promotes PC cell survival, TGF-β signal transduction facilitates PC attachment to endothelial cells, and Notch signaling is critical in vascular development and arterial-venous specification. Furthermore, current challenges facing the use of hiPSC-derived PCs are discussed, and their ongoing uses in neurodegenerative disease modeling are identified. Further investigations into PCs and surrounding cell interactions are needed to characterize the roles of brain PCs in various neurodegenerative disorders. Impact statement This article summarizes the work related to brain-specific pericytes (PCs) derived from human pluripotent stem cells (hPSCs). In particular, key signaling pathways regulating PC function, PC interactions with adjacent cells, and PC differentiation from hPSCs were discussed. Furthermore, current challenges facing the use of hPSC-derived PCs were identified, and their ongoing uses in neurodegenerative disease modeling were discussed. The review highlights the important role of cell-cell interactions in blood-brain barrier (BBB) models and neurodegeneration. The summarized findings are significant for establishing pluripotent stem cell-based BBB models toward the applications in drug screening and disease modeling.


Thrombotic microangiopathy without renal involvement: two novel mutations in complement-regulator genes.
ESSENTIALS: The differential diagnosis among thrombotic microangiopathies (TMAs) is challenging. We studied a case of TMA with neurologic symptoms, no renal impairment and normal ADAMTS-13 levels. Two novel mutations in complement factor I and thrombomodulin genes were identified. Complement-regulator genes can be involved in TMAs with normal ADAMTS-13 regardless of renal damage. Thrombotic microangiopathies (TMAs) often represent a challenge for clinicians, because clinical, laboratory, and even genetic features are not always sufficient to distinguish among different TMAs. The aim of this study was to investigate the pathogenetic mechanisms underlying an acute case of TMA with features of both thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS). We report the case of a 49-year-old woman who developed an acute TMA with neurologic involvement and no renal impairment. ADAMTS-13, von Willebrand factor, and complement-system biochemical characterization was performed on acute phase samples. Exome sequencing and direct Sanger sequencing of previously aHUS-associated genes were performed. The functional consequences of the thrombomodulin (THBD) mutation were investigated by in vitro expression studies. Despite a clinical diagnosis of TTP, the patient had normal ADAMTS-13 levels and increased VWF antigen levels with ultra-large von Willebrand factor multimers. C3, C4, and complement factors H and I (CFI) were normal. Molecular analysis confirmed two novel heterozygous mutations in CFI (c.805G>A, p.G269S) and THBD (c.1103C>T, p.P368L), and in vitro expression studies showed a reduction in the generation of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) caused by mutated THBD. This proinflammatory condition, associated with the p.G269S mutation in CFI, probably leads to a complement-mediated endothelial activation, with a relevant prothrombotic potential in case of transient environmental triggers. This study identified the first case of acute TMA without renal involvement but with neurological damage carrying two novel mutations in complement-regulator genes, highlighting the possible role of the complement system as a common pathogenetic mechanism in TMAs.


Adult enuresis and hyperthyroidism.
Two female patients with adult enuresis and enuretic syndrome were cured of their voiding disorders after treatment for hyperthyroidism. They were without symptoms at follow-up five and one-half and one and one-half years later. A relation between thyroid and bladder function is suggested which calls for further investigation in a controlled study.


Structure of N-myristoyltransferase with bound myristoylCoA and peptide substrate analogs.
N-myristoyltransferase (Nmt) attaches myristate to the N-terminal glycine of many important eukaryotic and viral proteins. It is a target for anti-fungal and anti-viral therapy. We have determined the structure, to 2.9 A resolution, of a ternary complex of Saccharomyces cerevisiae Nmt1p with bound myristoylCoA and peptide substrate analogs. The model reveals structural features that define the enzyme's substrate specificities and regulate the ordered binding and release of substrates and products. A novel catalytic mechanism is proposed involving deprotonation of the N-terminal ammonium of a peptide substrate by the enzyme's C-terminal backbone carboxylate.


Kinetic analyses of the activation of Glu-plasminogen by urokinase in the presence of fibrin, fibrinogen or its degradation products.
The kinetics of the activation of Glu-plasminogen (Glu-plg) and Lys-plasminogen (Lys-plg) by urokinase (UK) were studied in purified systems. The activation of plasminogen by UK in the purified systems followed Michaelis-Menten kinetics with a Michaelis constant (Km) of 1.45 microM and a catalytic rate constant (kcat) of 0.93/sec for Glu-plg as compared to 0.25 microM (Km) and 0.82/sec (kcat) for Lys-plg. In the presence of fibrin and fibrinogen or its plasmin degradation products (fragment D and fragment E), Km for Glu-plg hardly changed, whereas kcat for Glu-plg increased. Effect on increase in kcat was in the order of fibrin greater than fibrinogen greater than D greater than E. Fibrin, fibrinogen, D and E did not influence the activation of Lys-plg by UK. These results indicate that Glu-plg bound to fibrin, fibrinogen, D or E becomes easily activatable by UK. The activation of Lys-plg, however, is not influenced in the presence of fibrin, fibrinogen, D or E.


[Rheumatologic manifestations of endocrine disorders].
Diseases of different endocrine organs may cause symptoms at the locomotor system leading the patient to the rheumatologist. A correct interpretation of symptoms and findings the right may allow diagnosis and a causal treatment may be introduced. In this review the manifestations of disorders of the hypophysis, the thyroid, the parathyroid, the cortex and of diabetes mellitus at peripheral joints, the vertebral column, muscles, bones, and, as far as important for the rheumatologist, the peripheral nerve system are summarized. Carcinoid arthropathy is also mentioned.


Selective enrichment and characterization of a phosphorus-removing bacterial consortium from activated sludge.
Under alternating aerobic/anaerobic conditions and without additional carbon sources, a bacterial consortium consisting initially of 18 bacterial strains was obtained in a sequence batch reactor. The phosphorus removal capability could only be maintained using sterile filtrate of activated sludge as medium. The addition of calcium and magnesium salts, as well as vitamins and trace elements, to autoclaved sterile filtrate of activated sludge was not sufficient to achieve stable phosphorus removal. A further enrichment by subcultivation on solid, agar, freezing, and shortening of the aerobic and anaerobic phases led to a defined bacterial consortium consisting of four strains. On the basis of physiological and chemotaxonomic characterization, and partial 16S rRNA sequencing, one of the organisms was identified as Delftia acidovorans. A further isolate belonged to the Bacillus cereus group, and the third isolate was identified as Microbacterium sp.. The remaining strain seems to represent a new genus within the Flavobacteriaceae. Under continuous chemostat conditions, this consortium was able to remove up to 9.6 mg P/l phosphate in the aerobic phase and released up to 8.5 mg/l in the anaerobic phase. Up to 25 mg P-polyphosphate/g dry mass was stored under aerobic conditions.


Alternately π-Stacked Systems Assisted by o-Carborane: Dual Excimer Emission and Color Modulation by Bcage -Methylation.
Herein, we report the unique solid-state excimer emission of three types of acridine-tethered o-carboranes with variable degrees of methylation at the o-carborane unit. They all showed columnar packing structures based on dimer formation, and two types of π-overlapping motifs were alternately stacked. From the photoluminescence (PL) measurements on the crystalline samples, it was found that three types of luminescence bands can simultaneously appear: monomer emission, excimer emission from the moderately π-stacked intra-dimer unit, and excimer emission from the widely π-stacked inter-dimer unit. Consequently, the PL colors were drastically changed by the steric effect of the methyl groups, with a strong correlation found between the π-overlapping and excimer character. In addition, variable-temperature PL measurements revealed that these PL species should be in thermal equilibrium at room temperature, with the intensity ratios sensitive toward temperature changes.


New microbioassays based on biomarkers are more sensitive to fluvial water micropollution than standard testing methods.
Recent investigations suggest that, despite lack of lethality in validated bioassays, micropollutants in surface waters could induce sublethal toxicity in sensitive taxa, jeopardizing their biological performance and eventually leading to populations' extinction. A broader array of testing species, the miniaturization of bioassays and the development of reliable biomarkers of damage are sought in order to improve ecological relevance and cost efficiency of environmental monitoring. Our aim is to assess the different sensitivity of validated bioassays and new approaches using biomarkers as sensitive endpoints of toxicity in spores of Polystichum setiferum and Danio rerio embryos. Six water samples were collected in Tagus basin in summer and winter. Samples tested induce no acute toxicity in validated methods (algae growth inhibition and daphnia mobility inhibition). Summer water samples induced acute membrane damage (lipid peroxidation) in Danio rerio embryos and hormetic increases in fern spore mitochondrial activity. One of the samples dramatically reduced mitochondrial activity indicating severe acute sublethal phytotoxicity. All the winter samples induced significant decreases in fern spore mitochondrial activity and membrane damage increases in Danio rerio embryo. Furthermore, three samples induced lethal phytotoxicity in fern spores. We conclude that the new microbioassays show a better sensitivity to fluvial water micropollution and confirm the necessity to test critical life stages such as development and provide cost-efficient methods for environmental monitoring.


The Role of Pediatric Nutrition as a Modifiable Risk Factor for Precocious Puberty.
Puberty is a critical phase of growth and development characterized by a complex process regulated by the neuroendocrine system. Precocious puberty (PP) is defined as the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal. The timing of puberty has important public health, clinical, and social implications. In fact, it is crucial in psychological and physical development and can impact future health. Nutritional status is considered as one of the most important factors modulating pubertal development. This narrative review presents an overview on the role of nutritional factors as determinants of the timing of sexual maturation, focusing on early-life and childhood nutrition. As reported, breast milk seems to have an important protective role against early puberty onset, mainly due to its positive influence on infant growth rate and childhood overweight prevention. The energy imbalance, macro/micronutrient food content, and dietary patterns may modulate the premature activation of the hypothalamic-pituitary-gonadal axis, inducing precocious activation of puberty. An increase in knowledge on the mechanism whereby nutrients may influence puberty will be useful in providing adequate nutritional recommendations to prevent PP and related complications.


Elemental composition of two coexisting Daphnia species during the seasonal course of population development in Lake Constance.
In 1986 and 1987 the seasonal course of population density, life history traits and biomass composition (CHN-elemental and ash) of two coexisting Daphnia species from L. Constance (Überlinger See) were studied. The two daphnids are morphologically similar, but demonstrate different seasonal variation of behaviour (i.e. diurnal vertical migration). With the exception of nitrogen content, the mean biomass composition of adults and that of eggs were significantly different: the dry biomass of eggs (adults) contained on average 55.6 (46.1) % C, 7.9 (6.5) % H, 9.7 (9.7) % N, and 10.0 (23.8) % ash. These values were similar to those of other daphnids; it may be concluded that the average daphnid composition is not species specific, but is determined mainly by the position in the life cycle and by the nutritional state of the animal. A distinct seasonal variation in the elemental composition of the biomass of adult daphnids was observed. It related significantly to the concentration of food, as indicated by the epilimnetic chlorophyll-a concentrations and by Secchi depth. From the amplitude of seasonal variation of elemental composition and from the shape of relationships between the elemental composition of daphnids and their food, it can be concluded that in summer the non-migrating D. galeata lives under stronger food limitation than the migrating H. hyalina. In spring, there were no differences in the biomass composition of either species. In summer, the adult fcmales of D. galeata contained significantly less carbon, and hydrogen than those of D. hyalina. In most parameters of biomass (i.e. biomass composition of adults) and of life history (i.e. clutch size, mean adult weight), D. galeata displayed higher coefficients of variation. A tendency in D. galeata to have peaks of population development carlier in the season and in D. hyalina to have them towards autumn was observed. These contrasting responses of the populations development, the seasonal variability of the biomass composition seem to support the view of Geller (1986) who called D. galeata and D. hyalina "exploitative" and "conservative" strategists respectively.


Correction: Blood pressure control in chronic kidney disease: A cross-sectional analysis from the German Chronic Kidney Disease (GCKD) study.
[This corrects the article DOI: 10.1371/journal.pone.0202604.].


Influence of antimicrobial additives on the formation of rosin nanofibers via electrospinning.
In this study, we describe the influence of antimicrobial additives on the formation of rosin fibers by using electrospinning technique. Systematic experiments were performed to fabricate the rosin fibers via electrospinning and we tried to reduce the size of the fibers by mixing some additives such as triethylbenzylammonium chloride (TEBAC), chitosan and silver nitrate in the rosin polymer solution. The morphology, structure and thermal properties of the electrospun rosin fibers were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy and thermogravimetry (TGA). Rosin fibers with a diameter of the order of nanoscale were achieved by the use of TEBAC additive. The antimicrobial activity of the resultant fibers was checked by the antimicrobial disc diffusion test. All the rosin fibers showed excellent antibacterial activity against the gram negative bacteria and feeble activity against the gram positive bacteria. The present study demonstrated that the electrospun rosin fibers can be utilized for potential antimicrobial products.


[Continuous peridural anesthesia--results of fractionated application in comparison to catheter infusion].
This report presents 100 epidural analgesias using a catheter in a high risk group. Two groups are compared, one with intermittent manual injections, the other with constant infusion rate (CIR) by means of a syringe with bupivacaine solution 0,5% and a pump. The analgetic effect was stable, without fluctuations and was adequate during the first and the second stage of labour in the group with CIR. The CIR avoids plasma peaks with transient hypoxemia of the fetus. The high blood pressure in patients with severe pregnancy induced hypertension is more decreased with this technique. In comparison to deliveries without epidural analgesia the instrumental delivery rate was higher, the fetal outcome was equal. Severe complications are not seen. The indicated use of the epidural analgesia with CIR is recommended.


Can elbow-extension test be used as an alternative to radiographs in primary care?
To evaluate the ability of elbow extension, with the patient in a supine position, as a diagnostic test of an insignificant injury, with the purpose of avoiding unnecessary radiographs. Seventy patients suffering from an acute elbow injury were examined at the accident and emergency department. Inability to fully actively extend the elbow in a supine position was defined as a positive diagnostic test. Radiographs were interpreted by a consultant radiologist, blinded to all clinical examination results. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios along with their 95% confidence intervals were calculated for the elbow-extension test. Forty out of 70 patients had a positive test. Elbow fracture or dislocation was identified radiographically in 22 patients with positive test (sensitivity 92%). Two out of 30 (with negative test) had a hairline radial head fracture, which was found on radiographs (specificity 61%). Elbow extension as a diagnostic test in a primary care setting can predict severe elbow injuries and can be safely used in practices with no radiology facilities.


Effects of temperature, surfactants and skin location on the dermal penetration of haloacetonitriles and chloral hydrate.
Dermal exposure has been recognized as an important contributor to the total internal dose to disinfection-by-products (DBPs) in water. However, the effect of the use of surfactants, water temperature and area of the body exposed to DBPs on their dermal flux has not been characterized and was the focus of the present study using an in-vitro system. The dermal flux of mg/l concentrations of haloacetonitriles and chloral hydrate (CH), important cytotoxic DBPs, increased by approximately 50% to 170% with increasing temperature from 25 °C to 40 °C. The fluxes for the torso and dorsum of the hand were much higher than that of palm and scalp skin. An increase in flux was observed for chloroacetonitrite and dichloroacetonitrile, two less lipophilic HANs, but not for trichloroacetonitrile or CH, with the addition of 2% sodium lauryl sulfate or 2% sodium laureth sulfate, two surfactants commonly used in soaps and shampoos used in showering and bathing. Thus, factors such as temperature, surfactants and skin location affect dermal penetration and should be considered when evaluating dermal absorption.


"Early" delayed sternal closure following pediatric cardiac surgery.
Delayed sternal closure is commonly used following pediatric cardiopulmonary bypass surgery for many reasons including support of the failing myocardium. We hypothesized that, as a result of improvements in perioperative care, sternal closure could be achieved at an earlier postoperative time than the 3 to 5 days typically reported in the literature. Retrospective chart review of all bypass surgery (n = 585) performed in a single center over a 3-year period (2000-2002). We identified 66 children (11.3%), median age 5 days old, who underwent delayed sternal closure. In 60 of these patients, sternal closure was achieved at a median (interquartile) postoperative time of 21 hours (18 to 40 hours). The most common indication was inadequate hemostasis, although early sternal closure was also achieved in the subgroup with poor myocardial function as the primary indication at a median of 36 hours (21 to 44 hours). There was no noticeable hemodynamic, respiratory or metabolic compromise following sternal closure, although patients with poor myocardial function tended to have a lower mean blood pressure than those with inadequate hemostasis (ANOVA, p = 0.02). The overall mortality was 19.7% (13 of 66), with a median duration of ventilation and intensive care stay among survivors of 3.8 days (2.4 to 6.3 days) and 4.8 days (3.7 to 7.9 days), respectively. Delayed sternal closure is possible at an earlier stage than previously reported.


Can changes in midsole bending stiffness of shoes affect the onset of joint work redistribution during a prolonged run?
This study aimed to investigate if changing the midsole bending stiffness of athletic footwear can affect the onset of lower limb joint work redistribution during a prolonged run. Fifteen trained male runners (10-km time of <44 min) performed 10-km runs at 90% of their individual speed at lactate threshold (i.e., when change in lactate exceeded 1 mmol/L during an incremental running test) in a control and stiff shoe condition on 2 occasions. Lower limb joint kinematics and kinetics were measured using a motion capture system and a force-instrumented treadmill. Data were acquired every 500 m. Prolonged running resulted in a redistribution of positive joint work from distal to proximal joints in both shoe conditions. Compared to the beginning of the run, less positive work was performed at the ankle (approximately 9%; p ≤ 0.001) and more positive work was performed at the knee joint (approximately 17%; p ≤ 0.001) at the end of the run. When running in the stiff shoe condition, the onset of joint work redistribution at the ankle and knee joints occurred at a later point during the run. A delayed onset of joint work redistribution in the stiff condition may result in less activated muscle volume, because ankle plantar flexor muscles have shorter muscles fascicles and smaller cross-sectional areas compared to knee extensor muscles. Less active muscle volume could be related to previously reported decreases in metabolic cost when running in stiff footwear. These results contribute to the notion that footwear with increased stiffness likely results in reductions in metabolic cost by delaying joint work redistribution from distal to proximal joints.


Thermo-electrochemical redox flow cycle for continuous conversion of low-grade waste heat to power.
Here we assess the route to convert low grade waste heat (< 100 °C) into electricity by leveraging the temperature dependency of redox potentials, similar to the Seebeck effect in semiconductor physics. We use fluid-based redox-active species, which can be easily heated and cooled using heat exchangers. By using a first principles approach, we designed a redox flow battery system with Fe(CN)63-/Fe(CN)64- and I-/I3- chemistry. We evaluate the continuous operation with one flow cell at high temperature and one at low temperature. We show that the most sensitive parameter, the temperature coefficient of the redox reaction, can be controlled via the redox chemistry, the reaction quotient and solvent additives, and we present the highest temperature coefficient for this RFB chemistry. A power density of 0.6 W/m2 and stable operation for 2 h are achieved experimentally. We predict high (close to Carnot) heat-to-power efficiencies if challenges in the heat recuperation and Ohmic resistance are overcome, and the temperature coefficient is further increased.


The infrarenal aortic diameter in relation to age: only part of the population in older age groups shows an increase.
To resolve whether the infrarenal aortic diameter (IAD) continues to increase throughout life; to ascertain the relationship between IAD and age, sex, body size, and smoking status, and to determine whether these factors influence the IAD over the entire range of aortic diameters or only in a proportion. Combined cross-sectional data from two population-based screening programmes for abdominal aortic aneurysms (AAA) in Huntingdon (U.K.) and Rotterdam (The Netherlands). The antero-posterior diameter of the infrarenal aorta was measured. The influences of age, gender, body size and smoking status were examined. Data were analysed from 3066 women and 8270 men. In men, mean IAD rose from 20.7 mm to 23.5 mm in the older age groups. However, IADs remained constant below the 75th perentile in men and the 85th percentile in women. Similarly only the top 15-25% of the aortic diameters were larger in smokers compared with non-smokers. The aortic diameter increased with age in only a minority of the population. Furthermore, known risk factors for AAA contributed to aortic dilatation in only the upper tail of the frequency distribution. Thus only 25% of men and 15% of women may be prone to aortic dilatation.


Hollow silica reinforced magnesium nanocomposites with enhanced mechanical and biological properties with computational modeling analysis for mandibular reconstruction.
The present study investigates Mg-SiO2 nanocomposites as biodegradable implants for orthopedic and maxillofacial applications. The effect of presence and progressive addition of hollow silica nanoparticles (0.5, 1, and 1.5) vol.% on the microstructural, mechanical, degradation, and biocompatibility response of pure Mg were investigated. Results suggest that the increased addition of hollow silica nanoparticles resulted in a progressive increase in yield strength and ultimate compressive strength with Mg-1.5 vol.% SiO2 exhibiting superior enhancement. The response of Mg-SiO2 nanocomposites under the influence of Hanks' balanced salt solution revealed that the synthesized composites revealed lower corrosion rates, indicating rapid dynamic passivation when compared with pure Mg. Furthermore, cell adhesion and proliferation of osteoblast cells were noticeably higher than pure Mg with the addition of 1 vol.% SiO2 nanoparticle. The biocompatibility and the in vitro biodegradation of the Mg-SiO2 nanocomposites were influenced by the SiO2 content in pure Mg with Mg-0.5 vol.% SiO2 nanocomposite exhibiting the best corrosion resistance and biocompatibility when compared with other nanocomposites. Enhancement in mechanical, corrosion, and biocompatibility characteristics of Mg-SiO2 nanocomposites developed in this study are also compared with properties of other metallic biomaterials used in alloplastic mandibular reconstruction in a computational model.


Large mode area waveguides with polarization functions by volume ultrafast laser photoinscription of fused silica.
We present optical designs allowing large mode area light guiding by ultrafast laser photoinscription of bulk fused silica. If usual concepts are based on large core and depressed cladding, evanescently coupled multicore waveguides with coherent mode superposition can be effective solutions, where the introduction of nanostructured defects determines additional polarization functions.


Cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation product levels in acute ischemic stroke with advanced cancer.
Although several studies have reported various causes of ischemic stroke in patients with cancer, only a few have evaluated the clinical relevance of ischemic stroke pathogenesis to cancer. The aim of the present study was to elucidate the clinical characteristics of cancer-associated ischemic stroke. We evaluated 154 ischemic stroke patients without cancer and 57 ischemic stroke patients with cancer who had either received continuous treatment for cancer within 5 years before to the onset of ischemic stroke, or who had been diagnosed with cancer within 1 year after the onset of ischemic stroke. Cancer patients were grouped into "cancer-associated ischemic stroke," the "conventional ischemic stroke," or "other." A total of 15 patients (26%) were classified into the cancer-associated ischemic stroke in cancer patients. In univariate analysis of the cancer-associated ischemic stroke and the others, there were significant differences in the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d-dimer, fibrin degradation product and hemoglobin. With multivariate regression analysis of those factors, the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of D-dimer and fibrin degradation product remained as statistically independent factors, which were associated with cancer-associated ischemic stroke (n = 111, χ(2) =67.21, P < 0.0001). In acute ischemic stroke, the cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation products, even after controlling hypertension, hyperlipidemia and advanced cancer (clinical stage IV).


Visits to US emergency departments by 20- to 29-year-olds with toothache during 2001-2010.
Visits to emergency departments (EDs) for dental symptoms are on the rise, yet reliance on EDs for dental care is far from ideal. ED toothache visits represent opportunities to improve access to professional dental care. This research focuses on 20- to 29-year-olds, who account for more ED toothache visits than do other age groups. The authors analyzed publicly available ED visit data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2001 through 2010. They assessed trends in ED toothache visit rates compared with back pain and all cause ED visits during the past decade. The authors used NHAMCS data for years 2009 and 2010 to characterize the more recent magnitude, relative frequency, and independent risk factors for ED toothache visits. Statistical analyses accounted for the complex sampling design. The average annual increase in ED visit rates among 20- to 29-year-olds during 2001-2010 was 6.1% for toothache, 0.3% for back pain, and 0.8% for all causes of ED visits. In 2009 and 2010, 20- to 29-year-olds made an estimated 1.27 million ED visits for toothaches and accounted for 42% of all ED toothache visits. Toothache was the fifth most common reason for any ED visit and third most common for uninsured ED visits by 20- to 29-year-olds. Independent risk factors for ED toothache visits were being uninsured or Medicaid-insured. Younger adults increasingly rely on EDs for toothaches-likely because of barriers to accessing professional dental care. Expanding dental coverage and access to affordable dental care could increase options for timely dental care and decrease ED use for dental symptoms. Though additional research is needed to better understand why younger adults disproportionately use the ED for toothaches, findings from this study suggest the importance of maintaining access to a dental home from childhood through adolescence and subsequently into early adulthood.


Osteoprotegerin and B-type natriuretic peptide in non-ST elevation acute coronary syndromes: relation to coronary artery narrowing and plaques number.
To analyse osteoprotegerin (OPG), and B-type natriuretic peptide (BNP) levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. OPG has been found in several tissues, including the cardiovascular system, BNP is selectively produced by myocardial cells. 178 consecutive patients were classified in three groups: stable angina (SA), unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and control group, measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-, 2- , 3- or 4- vessels disease), and to the stenoses degree by Duke Jeopardy score. OPG levels were higher in patients respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with NSTE-ACS had higher OPG level with respect to SA patients (11.8+/-7.1 pmol/l p<0.001). A positive relation was found between OPG levels and number of coronary plaques by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with NSTE-ACS respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in multivessels vs 1-vessel disease (p<0.001). Patients with NSTE-ACS show high OPG levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the coronary disease progression. BNP is also increased during NSTE-ACS and more associated to coronary narrowing.


Physical activity and amyloid beta in middle-aged and older adults: A systematic review and meta-analysis.
One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is associated with decreased dementia risk, and one potential path could be through Aβ levels modulation. We aimed to explore the relationship between physical activity and Aβ in middle-aged and older adults. A systematic search of PubMed, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, and SPORTDiscus was performed from inception to the 28th of April 2022. Studies were eligible if they included physical activity and Aβ data in adults aged 45 years or older. Multi-level meta-analyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβ levels. In total, 37 articles were included (8 randomized controlled trials, 3 non-randomized controlled trials, 4 prospective longitudinal studies, and 22 cross-sectional studies). The overall effect size of physical activity interventions on changes in blood Aβ was medium (pooled standardized mean difference = -0.69, 95% confidence interval (95%CI): -1.41 to 0.03; I2 = 74.6%). However, these results were not statistically significant, and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid (CSF) and brain Aβ. Data from observational studies were examined based on measurements of Aβ in the brain using positron emission tomography scans, CSF, and blood. Higher physical activity was positively associated with Aβ only in the CSF (Estimate r = 0.12; 95%CI: 0.05-0.18; I2 = 38%). Physical activity might moderately reduce blood Aβ in middle-aged and older adults. However, results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies. In observational studies, higher levels of physical activity were positively associated with Aβ only in CSF. Therefore, further research is needed to understand the modulating role of physical activity in the brain, CSF, and blood Aβ, as well as its implication for cognitive health.


Neuroenhancement of surgeons during robotic suturing.
The initial phases of robotic surgical skills acquisition are associated with poor technical performance, such as low knot-tensile strength (KTS). Transcranial direct-current stimulation (tDCS) can improve force and accuracy in motor tasks but research in surgery is limited to open and laparoscopic tasks in students. More recently, robotic surgery has gained traction and is now the most common approach for certain procedures (e.g. prostatectomy). Early-phase robotic suturing performance is dependent on prefrontal cortex (PFC) activation, and this study aimed to determine whether performance can be improved with prefrontal tDCS. Fifteen surgical residents were randomized to either active then sham tDCS or sham then active tDCS, in two counterbalanced sessions in a double-blind crossover study. Within each session, participants performed a robotic suturing task repeated in three blocks: pre-, intra- and post-tDCS. During the intra-tDCS block, participants were randomized to either active tDCS (2 mA for 15 min) to the PFC or sham tDCS. Primary outcome measures of technical quality included KTS and error scores. Significantly faster completion times were observed longitudinally, regardless of active (p < 0.001) or sham stimulation (p < 0.001). KTS was greater following active compared to sham stimulation (median: active = 44.35 N vs. sham = 27.12 N, p < 0.001). A significant reduction in error scores from "pre-" to "post-" (p = 0.029) were only observed in the active group. tDCS could reduce error and enhance KTS during robotic suturing and warrants further exploration as an adjunct to robotic surgical training.


Modulation of 5-HT1C receptors and phosphoinositide system by ethanol consumption in rat brain and choroid plexus.
The effect of chronic ethanol consumption (60 days) on 5-HT1C receptors as measured by [3H]mesulergine binding in the hippocampus, cortex, and choroid plexus of rats was investigated. The 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus was also investigated. It was observed that chronic ethanol treatment significantly increased the 5-HT-stimulated [3H]inositol 1-phosphate ([3H]IP1) formation, as well as the density (Bmax) of 5-HT1C receptors without causing a significant change in affinity (KD) of [3H]mesulergine binding in rat choroid plexus. It was also observed that chronic ethanol consumption had no significant effect on the Bmax or KD of 5-HT1C receptor binding sites in the hippocampus and cortex brain regions of rats. These results thus suggest that chronic ethanol consumption causes an up-regulation of both 5-HT1C receptors and 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus but has no significant effects on the 5-HT1C receptors in brain. These results also suggest that 5-HT1C receptors and their functional response may be involved in the pathogenesis of alcohol dependence.


A role for Syk-kinase in the control of the binding cycle of the beta2 integrins (CD11/CD18) in human polymorphonuclear neutrophils.
A fine control of beta(2) integrin (CD11/CD18)-mediated firm adhesion of human neutrophils to the endothelial cell monolayer is required to allow ordered emigration. To elucidate the molecular mechanisms that control this process, intracellular protein tyrosine signaling subsequent to beta(2) integrin-mediated ligand binding was studied by immunoprecipitation and Western blotting techniques. The 72-kDa Syk-kinase, which was tyrosine-phosphorylated upon adhesion, was found to coprecipitate with CD18, the beta-subunit of the beta(2) integrins. Moreover, inhibition of Syk-kinase by piceatannol enhanced adhesion and spreading but diminished N-formyl-Met-Leu-Phe-induced chemotactic migration. The enhancement of adhesiveness was associated with integrin clustering, which results in increased integrin avidity. In contrast, piceatannol had no effect on the surface expression or on the affinity of beta(2) integrins. Altogether, this suggests that Syk-kinase controls alternation of beta(2) integrin-mediated ligand binding with integrin detachment.


Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells.
The antidepressants milnacipran and paroxetine are used clinically worldwide. In the present study, we report here the effects of treatment with milnacipran and paroxetine on the functional activity, binding sites, and mRNA of the norepinephrine (NE) transporter (NET) in cultured bovine adrenal medullary cells. In acute treatment with antidepressants for 20 min, both milnacipran and paroxetine competitively inhibited NET function in cultured adrenal medullary cells. Prolonged treatment of adrenal medullary cells with milnacipran produced time (48-96h)- and concentration (35-355 nM)-dependent increases in [3H]NE uptake and [3H]DMI binding without any increase in NET mRNA. At a high concentration (800 nM, 72 h), paroxetine suppressed [3H]NE uptake. To examine whether milnacipran-induced [3H]NE uptake is mediated by newly synthesized mRNAs or proteins, we used actinomycin D, an inhibitor of DNA-dependent RNA polymerase, and cycloheximide, an inhibitor of ribosomal protein synthesis. Cycloheximide (1 micorM, 72 h) abolished the effect of milnacipran on [3H]NE uptake, while the stimulatory effect of milnacipran was observed in actinomycin D-treated cells. The present findings suggest that prolonged exposure to milnacipran up-regulates the NET function, probably through a post-transcriptional process of NET or other proteins.


Climate change driven hyposalinity as a selective agent in the littoral mesoherbivore Idotea balthica.
Climate change will include a decrease in seawater salinity in the Baltic Sea. We quantified the effects of the projected future desalination on survival of the early life stage of the littoral herbivore Idotea balthica. We collected egg-bearing Idotea from three range-margin Baltic Sea populations, we exposed half of each brood to either current (6‰) or future salinity (3.5‰). We genotyped a subsample of each brood to analyse patterns of allelic change and to identify genomic regions targeted by selection. The survival was overall reduced by hyposalinity and broods varied in response to hyposalinity implying genetic variation in tolerance, with a stronger decrease in genetic diversity in future salinity. Finally, we identified proteins with crucial roles in basic cellular functions. This study indicates that projected future northern Baltic Sea hyposalinity will not just hamper I. balthica survival, but its selective pressure may also affect genetic diversity and cell physiology.


Retroperitoneal Laparoscopic Resolution of Posas Abscess: Case Reports and Review of the Literature.
Psoas abscess is a rare pathological entity being retroperitonescopy an unusual therapeutic modality for its resolution. The objective is to present and describe five patients with a diagnosis of psoas abscess that were resolved by retroperitoneoscopy in our institution and then carried out a non-systematic review of the literature. The mean age was 58.8 years and 80% were male. All patients had back pain and none had therapeutic resolution with conservative treatment. 60% of the patients had a methicillin sensitive Staphyylococus Aureus. In the follow-up with a mean of 10.2 months, no recurrence was observed. Early diagnosis of psoas abscess is important for its correct resolution. In our small series of patients, retroperitoneoscopy was an effective treatment.


Multinucleated giant cells in AIDS encephalopathy: an immunohistochemical study.
We report the neuropathological findings of 5 post-mortem cases of AIDS. The most common causes of the death were multiple opportunistic infections associated with cutaneous and/or visceral Kaposi sarcoma in two cases. Cerebral edema, demyelination and spongiosis of the white matter were present but the most remarkable finding was the presence of multinucleated giant cell (MGC) within and nearby microglial nodules. On immunohistochemical investigation MGC and microglial cells exhibit positive stain only for RCA I and Ferritin, while immunohistochemical markers for astrocytes, neurons, macrophages, histiocytes, lymphocytes and endothelial cells were negative. No microrganism, nor viral inclusions were detected. These results support the hypothesis that MGC may be derived from microglial cells.


The impact of skin calcinosis on digital ulcers in patients with SSc: clinical and prognostic stratification using the "wound bed score".
Digital ulcers (DUs) represent one of the major burdens for patients with systemic sclerosis (SSc), especially when associated with skin calcinosis (SC). The aim of this work is to evaluate the impact of SC in DUs of patients with SSc for clinical characteristics and prognosis assessed by the wound bed score (WBS). We prospectively enrolled 55 patients with DUs and SSc followed in our dedicated wound care clinic. For all the patients we collected clinical and anthropometric data and characteristics of the DU, and we calculated the WBS for each DU. Ninety-nine DUs were evaluated (24 with SC). SC was prevalent in limited cutaneous SSc (75%) and in patients with longer disease duration (P = 0.02). SC-DUs were prevalent at the fingertip (P = 0.04). The healing time was significantly higher in patients with SC (10.4 ± 7.9 weeks) compared with non-SC (7.0 ± 5.7 weeks) P = 0.03. The WBS negatively correlated with the time to achieve complete healing (r = -0.237 P = 0.023) and the correlation was maintained in the non-SC (r = -0.46, P = 0.033). DUs in SSc patients with SC are common and difficult to heal. When DUs are treated in dedicated centres, the prognosis is good. The WBS is fast and easy and maybe commonly applied in clinical practice.