Constructive and unconstructive repetitive thought.
The author reviews research showing that repetitive thought (RT) can have constructive or unconstructive consequences. The main unconstructive consequences of RT are (a) depression, (b) anxiety, and (c) difficulties in physical health. The main constructive consequences of RT are (a) recovery from upsetting and traumatic events, (b) adaptive preparation and anticipatory planning, (c) recovery from depression, and (d) uptake of health-promoting behaviors. Several potential principles accounting for these distinct consequences of RT are identified within this review: (a) the valence of thought content, (b) the intrapersonal and situational context in which RT occurs, and (c) the level of construal (abstract vs. concrete processing) adopted during RT. Of the existing models of RT, it is proposed that an elaborated version of the control theory account provides the best theoretical framework to account for its distinct consequences.


Developing an outline for teleneurology curriculum: AAN Telemedicine Work Group recommendations.
The emerging field of teleneurology is delivering quality care to neurologic patients in increasingly numerous technologies and configurations. Teleneurology is well-positioned to address many of the logistical issues neurologists and their patients encounter today. However, formalized medical training has not caught up with this developing field, and there is a lack of formal education concentrating on the specific opportunities and challenges of teleneurology. Considering this, the American Academy of Neurology Telemedicine Work Group identified equivalencies with which any practitioner of teleneurology should be familiar. The purpose of this curriculum is not to define teleneurology or mandate where its use is appropriate, but rather to provide guidance on basic equivalencies that students, residents, and practitioners should know while practicing teleneurology. Comprehensive training in clinical bedside neurology is necessary to safely practice teleneurology and the components of this curriculum are an extension of that training. In this article, we offer a detailed discussion on the rationale for the contents of this curriculum and conclude by providing a model curriculum and an outline for evaluating residents in teleneurology.


HCA587 antigen expression in normal tissues and cancers: correlation with tumor differentiation in hepatocellular carcinoma.
The HCA587 gene, identified by serological analysis of recombinant cDNA expression library (SEREX) from a hepatocellular carcinoma (HCC) patient, encodes a new member of cancer-testis antigens. HCA587 mRNA expression in normal tissues and cancers has been previously reported. To estimate its immunogenicity to induce immune response, it is essential to analyze HCA587 expression at the protein level. In this study anti-HCA587 polyclonal antibody, termed "TC-1," was generated, and the expression of HCA587 protein was assessed by immunohistochemical staining in a panel of normal and tumor tissue sections. No HCA587 protein was shown in normal tissues except germ cells in testis and Purkinji cells in cerebellum. In HCC specimens the HCA587 protein was expressed in 37.1% (26 of 70) samples. The expressed protein was either located in the cytoplasm or nucleus depending on the individual samples. More importantly, there appears to be correlation between the tumor differentiation of HCC and HCA587 protein expression, ie, the lower differentiation, the higher percentage of protein expression. Coincidentally, seroreactivity showed that the Ab specific to recombinant HCA587 protein was detected only in the sera of three patients with poorly differentiated HCCs. HCA587 antigen was also expressed in different proportions in melanoma, lymphoma, pancreatic cancer, and lung cancer.


A small area analysis estimating the prevalence of addiction to opioids in Barcelona, 1993.
To determine the distribution of opioid use prevalence in small areas and its relation with socioeconomic indicators. Capture-recapture was applied using data from the Barcelona Drug Information System for 1993 (treatment demands, hospital emergency room visits, deaths from heroin acute adverse reaction and pre-trial prison admissions). To avoid dependence between sources, a log-linear regression model with interactions was fitted. For small neighbourhoods, where capture-recapture estimates were not obtainable, the Heroin Problem Index (HPI) was used to predict prevalence rates from a regression model. The correlation between estimated opioid use prevalence by neighbourhoods and their socioeconomic level was computed. The city's estimated prevalence was 12.9 opioid addicts per 1000 inhabitants aged 15 to 44 years (95% CI: 10.1, 17.2), which represents 9176 persons. The highest rate was found in the inner city neighbourhood. Comparing rates obtained for each neighbourhood with their unemployment rates, a high correlation coefficient was obtained (r = 0.80, p < 0.001). The main contribution of this study is that of combining capture-recapture with the HPI to produce small area prevalence estimates, which would not have been possible using only one method. Areas with higher socioeconomic status showed proportionally low addiction prevalences, but in depressed areas, prevalences varied widely.


The p53 response in single cells is linearly correlated to the number of DNA breaks without a distinct threshold.
The tumor suppressor protein p53 is activated by cellular stress. DNA double strand breaks (DSBs) induce the activation of the kinase ATM, which stabilizes p53 and activates its transcriptional activity. Single cell analysis revealed that DSBs induced by gamma irradiation trigger p53 accumulation in a series of pulses that vary in number from cell to cell. Higher levels of irradiation increase the number of p53 pulses suggesting that they arise from periodic examination of the damage by ATM. If damage persists, additional pulses of p53 are triggered. The threshold of damage required for activating a p53 pulse is unclear. Previous studies that averaged the response across cell populations suggested that one or two DNA breaks are sufficient for activating ATM and p53. However, it is possible that by averaging over a population of cells important features of the dependency between DNA breaks and p53 dynamics are missed. Using fluorescent reporters we developed a system for following in individual cells the number of DSBs, the kinetics of repair and the p53 response. We found a large variation in the initial number of DSBs and the rate of repair between individual cells. Cells with higher number of DSBs had higher probability of showing a p53 pulse. However, there was no distinct threshold number of breaks for inducing a p53 pulse. We present evidence that the decision to activate p53 given a specific number of breaks is not entirely stochastic, but instead is influenced by both cell-intrinsic factors and previous exposure to DNA damage. We also show that the natural variations in the initial amount of p53, rate of DSB repair and cell cycle phase do not affect the probability of activating p53 in response to DNA damage. The use of fluorescent reporters to quantify DNA damage and p53 levels in live cells provided a quantitative analysis of the complex interrelationships between both processes. Our study shows that p53 activation differs even between cells that have a similar number of DNA breaks. Understanding the origin and consequences of such variability in normal and cancerous cells is crucial for developing efficient and selective therapeutic interventions.


[Extrarenal purification of blood in patients with multiple organ failure: results and prognostic criteria].
Acetate hemodialysis (HD) with an artificial kidney an continuous hemofiltration were used in the treatment of 49 patients with the multiple organ failure syndrome (MOFS) developing as a complication of aortocoronary and mammary-coronary shunting and heart valve replacement. MOFS involved failure of the function of 3.5 +/- 0.2 vital organs on average. Acute circulatory disorders were observed in 100% of patients, acute renal failure in 75.5%, and perioperative myocardial infarction in 34.7%. In 93.9% of patients HD and HF were combined with forced ventilation of the lungs, in 97.9% with catecholamine infusion, in 26.5% with assisted circulation, and in 57.1% with the Swan-Ganz monitoring of the central hemodynamics and of oxygen transporting function of circulation. Multiple-modality intensive care resulted in survival of 21 (42.8%) patients. The survival of patients with MOFS depended on the number of involved organs, method of extracorporeal detoxication, and monitoring of central hemodynamics and oxygen-transporting function of the blood. Acute renal failure, respiratory distress syndrome, and shock deteriorated the prognosis for patients with MOFS.


Nuclear-targeted gold nanoparticles enhance cancer cell radiosensitization.
Radiation therapy aims to kill or inhibit proliferation of cancer cells while sparing normal cells. To enhance radiosensitization, we developed 40 nm-sized gold nanoparticles targeting the nucleus. We exploited a strategy that combined RGD and NLS peptides respectively targeting cancer cell and the nucleus to initiate cell-death activated by x-ray irradiation. We observed that the modified gold nanoparticles were either translocated in the nuclei or accumulated in the vicinity of the nuclei. We demonstrated that x-ray irradiation at 225 kVp energy reduced cell proliferation by 3.8-fold when the nuclear targeted gold nanoparticles were used. We determined that the radiation dose to have a 10% survival fraction was reduced from 11.0 Gy to 7.1 Gy when 10.0 µg ml-1 of the NLS/RGD/PEG-AuNP was incubated with A549 cancer cells. We conclude that the peptide-modified gold nanoparticles targeting the nucleus significantly enhance radiosensitization.


Clinical growth charts for pre-school children.
Growth standards are indicators for normal growth of the children and growth charts are important tools for their growth monitoring. Children from different populations are different in their growth pattern, it is important to create national standards for the growth of children in each population to develop local growth charts, and since these were not available in the Kingdom of Saudi Arabia (KSA), the aim of this study was to construct national growth standards and to develop growth charts for 0-5-years Saudi children. A cross-sectional study following World Health Organization (WHO) criteria in determining sample size was adopted, where by 24000 children from 5 regions in the KSA were selected during the period 1992 to 1995 to be the desired sample. One hundred and two Primary Health Care centers (PHCCs) were selected randomly from the 5 regions, from where the sample was drawn, and a special questionnaire was designed. Weight, height and head circumference were measured by standard procedures. The total number of children examined was 23821 (11913 boys and 11908 girls). Saudi (0-5-years) boys weight and height for age measurements were significantly different from girls. The same difference was found between urban and rural boys and girls and between boys and girls from the different regions of the country (p<0.05). These national standards derived from this study were used to develop national growth charts that are currently utilized to monitor growth in all Saudi health institutes.


Peripheral extent of the choroidal circulation by ultra-widefield indocyanine green angiography in healthy eyes.
To analyse the peripheral extent of choroidal circulation using ultra-widefield (UWF) indocyanine green angiography (ICGA) in healthy eyes. UWF ICGA images of 55 eyes of 36 healthy subjects were captured using the Optos California (Optos, Dunfermline, United Kingdom) in this prospective observational study. Images were analysed to locate the peripheral extent of the visible choroidal circulation, and the boundary was marked in ImageJ (v1.52). Each pixel annotated as the border of the choroidal circulation was projected individually to its anatomically correct location on the three-dimensional model eye, and spherical trigonometry was applied (using the Optos software) to calculate its respective radial distance from the centre of the optic disc in metric units (corrected by stereographic projection) for each quadrant. The mean area of the peripheral extent was estimated to be 893.2 mm2 (95% CI: 844.2 to 942.3 mm2). The mean distance (range) of this boundary from optic nerve centre was 18.22 mm (95% CI: 14.0 to 23.14 mm). Multiple regression analysis with age, gender, axial length or ethnicity showed no relationship. There was excellent inter-grader reproducibility, with intraclass correlation coefficients of 0.95 (95% CI: 0.80 to 0.99, p<0.001) for distance and 0.99 (95% CI: 0.988 to 0.999, p<0.001) for area measurements. The peripheral choroidal boundary may be defined using UWF ICGA. Knowledge of the normal extent and its variability is essential to understand the impact of disease on the choroidal vasculature.


Selective utilization of basic helix-loop-helix-leucine zipper proteins at the immunoglobulin heavy-chain enhancer.
The microE3 E box within the immunoglobulin heavy-chain (IgH) enhancer binds several proteins of the basic helix-loop-helix-leucine zipper (bHLHzip) class, including TFE3, USF1, and Max. Both TFE3 and USF have been described as transcriptional activators, and so we investigated their possible roles in activating the IgH enhancer in vivo. Although TFE3 activated various enhancer-based reporters, both USF1 and Max effectively inhibited transcription. Inhibition by USF correlated with the lack of a strong activation domain and was the result of the protein neutralizing the microE3 site. The effects of dominant-negative derivatives of TFE3 and USF1 confirmed that TFE3, or a TFE3-like protein, is the primary cellular bHLHzip protein that activates the IgH enhancer. In addition to providing a physiological role for TFE3, our results call into question the traditional view of USF1 as an obligate transcriptional activator.


The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.
The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases.


Adenovirus binds to rat brain microtubules in vitro.
We have found by negative staining electron microscopy that when similar concentrations of adenovirus and reovirus (viruses of about the same diameter, 75 to 80 nm, and density, 1.34 to 1.36 g/cm3) were incubated with a carbon support film containing microtubules, 72% of adenovirus on the grid, but only 32% (equivalent to random association) of reovirus, were associated with microtubules. Similar concentrations of both larger and smaller particles, such as polystyrene latex spheres and coliphage f2, also exhibited a low degree of interaction, viz., 17 to 37%, with microtubules. Moreover, 90% of microtubule-associated adenovirus binds to within +/- 4 nm of the edge of microtubules, but lower fractions (again equivalent to a random association) of the other particles bind to the edge of the microtubules. The mechanism behind this phenomenon, which we denote as "edge binding," is presently obscure; however, it provides us with a second, albeit empirical, method to distinguish between the microtubular association of adenovirus and other particles. We found that edge binding of adenovirus also occurred when adenovirus was initially placed on the carbon support film and then incubated with microtubules and when adenovirus and microtubules were mixed prior to placement on the support. In contrast, reovirus or the other particles prepared by similar techniques exhibited a random amount of edge binding. The binding of adenovirus appears to involve the hexon capsomers of the virion since (i) high resolution electron micrographs showed that the edge of the virus was in contact with the edge of the microtubules, and (ii) adenovirions briefly treated with formamide to remove pentons and fibers bind as efficiently as intact virions. Core structures, which were obtained by further formamide degradation of the virion, do not associate with microtubules. These observations support the hypothesis of Dales and Chardonnet (1973) that the transport of adenovirions within infected cells is mediated by interaction with microtubules.


uORF-Tools-Workflow for the determination of translation-regulatory upstream open reading frames.
Ribosome profiling (ribo-seq) provides a means to analyze active translation by determining ribosome occupancy in a transcriptome-wide manner. The vast majority of ribosome protected fragments (RPFs) resides within the protein-coding sequence of mRNAs. However, commonly reads are also found within the transcript leader sequence (TLS) (aka 5' untranslated region) preceding the main open reading frame (ORF), indicating the translation of regulatory upstream ORFs (uORFs). Here, we present a workflow for the identification of translation-regulatory uORFs. Specifically, uORF-Tools uses Ribo-TISH to identify uORFs within a given dataset and generates a uORF annotation file. In addition, a comprehensive human uORF annotation file, based on 35 ribo-seq files, is provided, which can serve as an alternative input file for the workflow. To assess the translation-regulatory activity of the uORFs, stimulus-induced changes in the ratio of the RPFs residing in the main ORFs relative to those found in the associated uORFs are determined. The resulting output file allows for the easy identification of candidate uORFs, which have translation-inhibitory effects on their associated main ORFs. uORF-Tools is available as a free and open Snakemake workflow at https://github.com/Biochemistry1-FFM/uORF-Tools. It is easily installed and all necessary tools are provided in a version-controlled manner, which also ensures lasting usability. uORF-Tools is designed for intuitive use and requires only limited computing times and resources.


Relation between pain location and disc pathology: a study of pain drawings and CT/discography.
The purpose of this study was to determine whether pain location indicated in pain drawings was related to the specific lumbar disc level(s) that was abnormal in appearance and painful upon discographic injection. Data were collected prospectively. This study was conducted in a spine specialty clinic. The study group consisted of 187 patients (118 men, 69 women; mean age = 37.2 years, range = 18-62 years) with low back pain with or without leg pain. All patients were undergoing computed tomography (CT)/discography at the three lowest lumbar levels for diagnostic purposes. Pain drawings were completed the day of but prior to undergoing discography. Discographic pain responses were recorded with respect to the similarity to the patient's clinical symptoms. Pain drawings were classified based on the presence or absence of pain in five areas: low back and/or buttocks, posterior thigh, posterior leg, anterior thigh, and anterior leg. The drawings were scored with the system described by Ransford et al. (1976, Spine 1: 127-34), and those likely to be indicative of psychological problems were analyzed separately (n = 43). Results were determined by analyzing the relation between the location of pain in the drawings and the specific lumbar disc level(s) found to be painful and disrupted by discography. There was a significant relation between pain location indicated in the drawing and the lumbar disc level(s) identified as clinically painful and disrupted by CT/discography (p < 0.05, chi-square). Pain limited to the low back and buttocks was frequently associated with the absence of disc pathology (58.3%). When pain in the posterior thigh or leg was present but there was no pain in the anterior drawing, patients frequently had a positive L5-S 1 disc (> or =75%). In patients with anterior thigh pain, with or without posterior thigh or leg pain, the L4-5 disc was frequently symptomatic (>63%). The pattern of no posterior thigh or leg pain but with pain radiating into the leg anteriorly was most commonly associated with the L3-4 disc (71.4%). The results of this study indicate that pain drawings may be helpful in identifying which specific discs are associated with pain complaints. As with any evaluation, the drawings should be considered in combination with findings from other assessments.


Heme oxygenase-1 and hemopexin gene polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity in China.
Objective: To assess whether the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) might be influenced by heme oxygenase-1 (HMOX1) and hemopexin (HPX) gene polymorphisms. Methods: A dynamic anti-tuberculosis treatment cohort was constructed, and the 1:4 matched nested case-control study was analysed. Eight single-nucleotide polymorphisms (SNPs) of the two genes were selected for genotyping and Bonferroni correction was performed to correct for multiple comparison. Results: Overall, 7.8% of patients developed ATDH. SNP rs1807714 in the HMOX1 gene had decreased effects on the risk of moderate and severe hepatotoxicity under the dominant and additive models, and hepatocellular injury under the additive model. SNP rs2682099 in the HPX gene had increased effects on the risk of moderate and severe hepatotoxicity under the recessive model. However, these associations disappeared after Bonferroni correction. Conclusion:HMOX1 and HPX gene polymorphisms might not be associated with susceptibility to ATDH in the Chinese population.


BIOPHOTONS IN RADIOBIOLOGY: INHIBITORS, COMMUNICATORS AND REACTORS.
Radiation-induced bystander effects refer to the production of signals from irradiated cells which induce responses in unirradiated, or bystander, cells. There has been a recent resurgence of interest in low-energy photon biology. This is due to concerns about health effects, increased use of biophoton imaging techniques, and the fact that biophotons can act as a bystander signal. This review discusses the history of light signaling in biology and potential mechanisms involved in the generation and transduction of signaling mechanisms. The role of photons in signaling in the animal and plant kingdoms is also reviewed. Finally, the potential to harness these mechanisms in radiation protection or therapy is discussed with emphasis on promising future directions for research.


Corneal curvature gradient map: a new corneal topography map to predict the corneal healing process.
To evaluate a new curvature gradient topography map to predict postoperative corneal remodeling. In this retrospective study, 32 eyes of 16 patients with myopia underwent excimer ablation surgery with a postoperative high curvature gradient. The new curvature gradient map (acquired immediately postoperatively) shows the difference between the curvatures of two points over the distance between them; it was compared to the tangential curvature difference map between 1 and 12 months postoperatively to determine their relationship. Corneas were divided into 12 regions for analysis: four 90°-wide sectors centered on 0°, 90°, 180°, and 270°. There were three subdivisions in each sector: central (radius: 0 to 2.75 mm), paracentral (radius: 2.75 to 3.25 mm), and peripheral (radius: 3.25 to 4.5 mm). Linear regression analysis was performed by region. The following regions had significant relationships between the initial curvature gradient and curvature difference between 1 and 12 months postoperatively: the paracentral zone of the 90° sector (P = .0145; R(2) = 0.1832) and both the central (P = .0034; R(2) = 0.2522) and paracentral (P = .0452; R(2) = 0.1271) zones of the 270° sector. The greatest average initial tangential curvature was in the 270° sector. The initial curvature gradient after surgery predicted change in tangential curvature over the subsequent 12 months in areas where initial tangential curvature was greatest. When the curvature gradient was high, the surface curvature modification remained in progress months after surgery.


Expression of the urokinase receptor in vascular endothelial cells is stimulated by basic fibroblast growth factor.
Basic fibroblast growth factor, a potent angiogenesis inducer, stimulates urokinase (uPA) production by vascular endothelial cells. In both basic fibroblast growth factor-stimulated and -nonstimulated bovine capillary endothelial and human umbilical vein endothelial cells single-chain uPA binding is mediated by a membrane protein with a Mr of 42,000. Exposure of bovine capillary or endothelial human umbilical vein endothelial cells to pmolar concentrations of basic fibroblast growth factor results in a dose-dependent, protein synthesis-dependent increase in the number of membrane receptors for uPA (19,500-187,000) and in a parallel decrease in their affinity (KD = 0.144-0.790 nM). With both cells, single-chain uPA binding is competed by synthetic peptides whose sequence corresponds to the receptor-binding sequence in the NH2-terminal domain of uPA. Exposure of bovine capillary endothelial cells to transforming growth factor beta 1, which inhibits uPA production and upregulates type 1 plasminogen activator inhibitor, the major endothelial cell plasminogen activator inhibitor, has no effect on uPA receptor levels. These results show that basic fibroblast growth factor, besides stimulating uPA production by vascular endothelial cells, also increases the production of receptors, which modulates their capacity to focalize this enzyme on the cell surface. This effect may be important in the degradative processes that occur during angiogenesis.


Silkworm cocoons inspire models for random fiber and particulate composites.
The bioengineering design principles evolved in silkworm cocoons make them ideal natural prototypes and models for structural composites. Cocoons depend for their stiffness and strength on the connectivity of bonding between their constituent materials of silk fibers and sericin binder. Strain-activated mechanisms for loss of bonding connectivity in cocoons can be translated directly into a surprisingly simple yet universal set of physically realistic as well as predictive quantitative structure-property relations for a wide range of technologically important fiber and particulate composite materials.


Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study.
Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances, in particular from insulin resistance. Accumulating evidence suggests that vitamin D deficiency may contribute to the development of insulin resistance. Hence, we aimed to examine the effect of vitamin D supplementation on metabolic and endocrine parameters in PCOS women. Fifty-seven PCOS women were included in the study. PCOS women received 20,000 IU cholecalciferol weekly for 24 weeks. Anthropometric measures, oral glucose tolerance test, and blood analyses of endocrine parameters were performed at baseline and after 12 weeks (V2) and 24 weeks (V3). Forty-six PCOS women finished the study. 25-hydroxyvitamin D [25(OH)D] levels significantly increased from 28.0±11.0 ng/ml at baseline to 51.3±17.3 and 52.4±21.5 at V2 and V3, respectively (p<0.001). We observed a significant decrease of fasting and stimulated glucose (V3, p<0.05) and C-peptide levels (V2 and 3, p<0.001) after vitamin D treatment. Moreover, triglyceride and estradiol levels significantly decreased at V3 (p=0.001) and V2 (p=0.022), respectively, whereas total cholesterol (V2, p=0.008) and LDL cholesterol levels (V2, p=0.005; V3, p=0.026) significantly increased after vitamin D treatment. There were no changes in androgens. At V2, 14 out of 46 PCOS women previously affected by menstrual disturbances (30.4%) reported improvement of menstrual frequency; at V3, 23 out of 46 women (50.0%), who were oligo- or amenorrheic at baseline reported improvement. Our results suggest that vitamin D treatment might improve glucose metabolism and menstrual frequency in PCOS women. Further randomized controlled trails are warranted to confirm our findings.


Synaptic Plasticity After Focal Cerebral Ischemia Was Attenuated by Gap26 but Enhanced by GAP-134.
Objective: Synaptic plasticity is critical for neurorehabilitation after focal cerebral ischemia. Connexin 43 (Cx43), the main component of the gap junction, has been shown to be pivotal for synaptic plasticity. The objective of this study was to investigate the role of the Cx43 inhibitor (Gap26) and gap junction modifier (GAP-134) in neurorehabilitation and to study their contribution to synaptic plasticity after focal ischemia. Methods: Time course expression of both total and phosphorylated Cx43 (p-Cx43) were detected by western blotting at 3, 7, and 14 d after focal ischemia. Gap26 and GAP-134 were administered starting from 3 d post focal ischemia. Neurological performances were evaluated by balance beam walking test and Y-maze test at 1, 3, and 7 d. Golgi staining and transmission electron microscope (TEM) detection were conducted at 7 d for observing dendritic spine numbers and synaptic ultrastructure, respectively. Immunofluorescent staining was used at 7 d for detection of synaptic plasticity markers, including synaptophysin (SYN) and growth-associated protein-43 (GAP-43). Results: Expression levels of both total Cx43 and p-Cx43 were increased after focal cerebral ischemia, peaking at 7 d. Compared with the MCAO group, Gap26 worsened the neurological behavior and decreased the dendritic spine number while GAP-134 improved the neurobehavior and increased the number of dendritic spines. Moreover, Gap26 further destroyed the synaptic structure, concomitant with downregulated SYN and GAP-43, whereas GAP-134 alleviated synaptic destruction and upregulated SYN and GAP-43. Conclusion: These findings suggested that Cx43 or the gap junction was involved in synaptic plasticity, thereby promoting neural recovery after ischemic stroke. Treatments enhancing gap junctions may be potential promising therapeutic measures for neurorehabilitation after ischemic stroke.


E-prescribing errors identified in a compounding pharmacy: a quality-improvement project.
Errors during the prescribing process can cause problems for patients. When the pharmacist intercepts a prescribing error, it can cause a delay, as the patient may not receive the medication until the problem is resolved. Electronic prescriptions are purported to reduce prescribing errors. However, studies have shown that electronic prescriptions can be prone to certain types of errors. Compounding pharmacies may present an additional obstacle for e-prescribing, as the prescribed medications are not commercially available and may not be listed in the e-prescribing software. The objectives of this study were to estimate the electronic prescription error rate in a compounding pharmacy, determine the most common error types, list the most common interventions pharmacists made, and estimate how long it took to resolve these errors. The study design was quality improvement with descriptive data. During the four weeks of data collection, the pharmacists were trained to complete a standardized data collection form when they identified an electronic prescription error. Percentages were calculated for new prescriptions, electronic prescriptions with errors, error types, and error resolution methods. In the four-week period of the study, there were 982 new prescriptions, 111 of which were electronic prescriptions. Of those 111 electronic prescriptions, 70 had errors. The electronic prescriptions error rate was 63%. The most common type of error was wrong entry field (70.3%). For this project, wrong entry field was defined to mean that the drug name was in the wrong field (81%) or that multiple entries were in the wrong field (7%). Pharmacists usually used their own judgment to resolve an error (67%). Many e-prescription errors were identified in this compounding pharmacy. When prescription errors happen, workflow and patient care are disrupted. Our goal is to discuss these findings with Surescripts and e-prescribing software companies to seek systems-based solutions.


Exposure of differentiated airway epithelial cells to volatile smoke in vitro.
Cigarette smoke (CS) is the predominant pathogenetic factor in the development of chronic bronchitis and chronic obstructive pulmonary disease. The knowledge about the cellular and molecular mechanisms underlying the smoke-induced inflammation in epithelial cells is limited. The aim of this study was to develop an in vitro model to monitor the effects of volatile CS on differentiated airway epithelial cells. The airway epithelial cell line MM-39 and primary human bronchial epithelial cells were cultivated as air-liquid interface cultures and exposed directly to volatile CS. We used two types of exposure models, one using ambient air, the other using humidified and warm air. Cytokine levels were measured by quantitative PCR and ELISA. Phosphorylation of p38 MAP kinase was assessed by Western blot analysis. To reduce the smoke-induced inflammation, antisense oligonucleotides directed against the p65 subunit of NF-kappaB were applied. Exposure of epithelia to cold and dry air resulted in a significant inflammatory response. In contrast, exposure to humidified warm air did not elicit a cellular response. Stimulation with CS resulted in upregulation of mRNA for IL-6 and IL-8 and protein release. Exposure to CS combined with heat-inactivated bacteria synergistically increased levels of the cytokines. Reactions of differentiated epithelial cells to smoke are mediated by the MAP kinase p38 and the transcription factor NF-kappaB. We developed an exposure model to examine the consequences of direct exposure of differentiated airway epithelial cells to volatile CS. The model enables to measure the cellular reactions to smoke exposure and to determine the outcome of therapeutic interventions.


Overweight and obesity in the eastern province of Saudi Arabia.
To describe anthropometric characteristics of participants and the influence of sociodemographic and cardiovascular risk factors involved in the prevalence of obesity in the eastern province of Saudi Arabia. In the year 2004, all Saudi residents in the Eastern province aged 30 years and above, were invited to participate in a community screening campaign for early detection of diabetes and hypertension. Demographic data, medical history, life habits, weight, height, blood pressure, and glucose concentration were recorded using a structured questionnaire. Obesity and overweight were defined by body mass index (BMI) >or=30 kg/m2 and 25-29.9 kg/m2, respectively. Logistic regression was used to predict the association of the significant factors with the prevalence of obesity. Out of 195,874 participants, the overall prevalence of obesity was 43.8%, while 35.1% were overweight. The prevalence of underweight was 1.3%. The peak prevalence of obesity was observed in the age group 50-59 years. Obesity was higher among women than men, higher in housewives, and among the less educated than others (p<0.0001). Linear regression analysis showed a strong proportional association of BMI with diabetes, hypertension, triglycerides and cholesterol, and an inverse proportional association with physical activity and smoking Obesity and overweight constitute an important health problem affecting a high proportion of Saudi population. Addressing associated factors, and enhancing public health education is an important aim to focus on for weight control.


[Drug treatment of depression in children and adolescents].
Antidepressants may increase suicidal behaviour in children and adolescents with depression, and should be used with great care. The article provides an overview of research that may guide the clinician when treating depression in young people. No medication should be given without a thorough evaluation of diagnoses and psychosocial problems. Psychoeducation and psychotherapy should be tried before medication is started. Fluoxetine is the first choice for depression. If it is not effective, a switch to another SSRI may prove effective. SSRIs are found to be more efficacious in adolescents than in children.


Reduced virulence of the MARTX toxin increases the persistence of outbreak-associated Vibrio vulnificus in host reservoirs.
Opportunistic bacteria strategically dampen their virulence to allow them to survive and propagate in hosts. However, the molecular mechanisms underlying virulence control are not clearly understood. Here, we found that the opportunistic pathogen Vibrio vulnificus biotype 3, which caused an outbreak of severe wound and intestinal infections associated with farmed tilapia, secretes significantly less virulent multifunctional autoprocessing repeats-in-toxin (MARTX) toxin, which is the most critical virulence factor in other clinical Vibrio strains. The biotype 3 MARTX toxin contains a cysteine protease domain (CPD) evolutionarily retaining a unique autocleavage site and a distinct β-flap region. CPD autoproteolytic activity is attenuated following its autocleavage because of the β-flap region. This β-flap blocks the active site, disabling further autoproteolytic processing and release of the modularly structured effector domains within the toxin. Expression of this altered CPD consequently results in attenuated release of effectors by the toxin and significantly reduces the virulence of V. vulnificus biotype 3 in cells and in mice. Bioinformatic analysis revealed that this virulence mechanism is shared in all biotype 3 strains. Thus, these data provide new insights into the mechanisms by which opportunistic bacteria persist in an environmental reservoir, prolonging the potential to cause outbreaks.


Pepper mild mottle virus, a plant virus associated with specific immune responses, Fever, abdominal pains, and pruritus in humans.
Recently, metagenomic studies have identified viable Pepper mild mottle virus (PMMoV), a plant virus, in the stool of healthy subjects. However, its source and role as pathogen have not been determined. 21 commercialized food products containing peppers, 357 stool samples from 304 adults and 208 stool samples from 137 children were tested for PMMoV using real-time PCR, sequencing, and electron microscopy. Anti-PMMoV IgM antibody testing was concurrently performed. A case-control study tested the association of biological and clinical symptoms with the presence of PMMoV in the stool. Twelve (57%) food products were positive for PMMoV RNA sequencing. Stool samples from twenty-two (7.2%) adults and one child (0.7%) were positive for PMMoV by real-time PCR. Positive cases were significantly more likely to have been sampled in Dermatology Units (p<10(-6)), to be seropositive for anti-PMMoV IgM antibodies (p = 0.026) and to be patients who exhibited fever, abdominal pains, and pruritus (p = 0.045, 0.038 and 0.046, respectively). Our study identified a local source of PMMoV and linked the presence of PMMoV RNA in stool with a specific immune response and clinical symptoms. Although clinical symptoms may be imputable to another cofactor, including spicy food, our data suggest the possibility of a direct or indirect pathogenic role of plant viruses in humans.


A modified oral screen appliance to prevent self-inflicted oral trauma in an infant with cerebral palsy: a case report.
Self-inflicted oral trauma occurs in a number of conditions with different etiologic and clinical characteristics. The management of such trauma also varies depending on the medical history of the patient; the etiology of the behavior; and the severity, frequency, and method of inflicting injury. This case report describes a modified oral screen placed in a 10-month-old female infant with cerebral palsy who had been having feeding problems caused by self-inflicted oral trauma. The modified oral screen effectively protected the wounds against further oral trauma to the lower lip and tongue without being fixed to the dentition.


Spin-orbit effects in electron transfer in neptunyl(VI)-neptunyl(V) complexes in solution.
The spin-orbit effects were investigated on the complexes involved in the electron self-exchange between Np(V) and Np(VI) in both the outer-sphere and inner-sphere mechanisms, the latter for binuclear complexes containing hydroxide, fluoride, and carbonate as bridging ligands. Results obtained with the variation-perturbation and the multireference single excitation spin-orbit CI calculations are compared. Both effects due to different relaxations of spinors within a multiplet (spin-orbit relaxation) and scalar (electrostatic) relaxation effects in the excited states are accounted for in the latter scheme. The results show that the scalar (electrostatic) relaxation is well described by the single-excitation spin-orbit CI, and that spin-orbit relaxation effects are small in the Np complexes, as in the lighter d-transition elements but in contrast to the main group elements.


Trends in femoroacetabular impingement research over 11 years.
Femoroacetabular impingement is the abutment between the proximal femur and the rim of the acetabulum. It is a common cause of labral injury that has been identified as an early cause of hip osteoarthritis. The diagnosis of femoroacetabular impingement of the hip is currently well defined in orthopedic surgery but should attract the attention of physicians in other disciplines. Conversely, much less is known about the etiology and natural history of femoroacetabular impingement.The goal of this study was to assess the number of articles published on femoroacetabular impingement over 11 years in orthopedic vs nonorthopedic medical journals, and to evaluate the quality of available evidence. PubMed and OvidSP databases were searched for articles on femoroacetabular impingement published from 1999 to 2009. Articles were characterized by publication type and journal type per year. Regression analysis was used to determine the effect of publication year on number of publications of each type. The search yielded 206 publications on femoroacetabular impingement during the evaluation period. Seventy-two percent were published in orthopedic journals. Overall, the number of publications increased exponentially with time. There was an increase in clinical trials over the course of the study period. However, studies with high-quality evidence were scarce. The increase in data from orthopedic and nonorthopedic disciplines is welcome. Nevertheless, high-quality evidence on femoroacetabular impingement is lacking. We believe the current trend toward evidence-based orthopedic surgery will impact future research on this relatively new disorder.


Drawing cartoon faces--a functional imaging study of the cognitive neuroscience of drawing.
We report a functional imaging study of drawing cartoon faces. Normal, untrained participants were scanned while viewing simple black and white cartoon line drawings of human faces, retaining them for a short memory interval, and then drawing them without vision of their hand or the paper. Specific encoding and retention of information about the faces were tested for by contrasting these two stages (with display of cartoon faces) against the exploration and retention of random dot stimuli. Drawing was contrasted between conditions in which only memory of a previously viewed face was available versus a condition in which both memory and simultaneous viewing of the cartoon were possible, and versus drawing of a new, previously unseen, face. We show that the encoding of cartoon faces powerfully activates the face-sensitive areas of the lateral occipital cortex and the fusiform gyrus, but there is no significant activation in these areas during the retention interval. Activity in both areas was also high when drawing the displayed cartoons. Drawing from memory activates areas in posterior parietal cortex and frontal areas. This activity is consistent with the encoding and retention of the spatial information about the face to be drawn as a visuo-motor action plan, either representing a series of targets for ocular fixation or as spatial targets for the drawing action.


Enteropathogens associated with diarrhea among military personnel during Operation Bright Star 96, in Alexandria, Egypt.
This study investigated the microbial causes of diarrheal disease among U.S. troops deployed near Alexandria, Egypt, during October 1995. Bacterial causes associated with 19 cases of diarrhea included: enterotoxigenic Escherichia coli (ETEC), 42% (21% heat-stable, 11% heat-labile, and 11% heat-stable/ heat-labile producers); enteropathogenic E. coli (5.3%); and enteroadherent E. coli (42%). Four cases of diarrhea were associated with enteroaggregative E. coli based on probe analysis for enteroaggregative heat-stable enterotoxin 1. Protozoan causes included; Entamoeba histolytica (11%), E. hartmanni (5%), E. nana (5%), Blastocystis hominis (5%), Chilomastix mesnili (11%), Dientamoeba fragilis (5%), Entamoeba coli (5%), and Cryptosporidium (5%). Shigella, Aeromonas, Plesiomonas, Vibrio, Campylobacter, and Salmonella were not detected. Of the eight ETEC cases, one was colonization factor antigen (CFA)/I only, one was both CFA/I and CFA/III, three were CFA/II, two were CFA/IV, and two were CFA-negative. Antibiograms of the ETEC and enteroadherent E. coli strains showed that all isolates were susceptible to norfloxacin, ciprofloxacin, and nalidixic acid but resistant to ampicillin, tetracycline, chloramphenicol, and sulfamethoxazole.


Nanococktail Based on AIEgens and Semiconducting Polymers: A Single Laser Excited Image-Guided Dual Photothermal Therapy.
Semiconducting polymers (SPs)-based dual photothermal therapy (PTT) obtained better therapeutic effect than single PTT due to its higher photothermal conversion efficiency. However, most dual PTT need to use two lasers for heat generation, which brings about inconvenience and limitation to the experimental operations. Herein, we report the development of "nanococktail" nanomaterials (DTPR) with 808 nm-activated image-guided dual photothermal properties for optimized cancer therapy. Methods: In this work, we co-encapsulated AIEgens (TPA-BDTO, T) and SPs (PDPPP, P) by using maleimide terminated amphiphilic polymer (DSPE-PEG2000-Mal, D), then further conjugated the targeting ligands (RGD, R) through "click" reaction. Finally, such dual PTT nanococktail (termed as DTPR) was constructed. Results: Once DTPR upon irradiation with 808 nm laser, near-infrared fluorescence from T could be partially converted into thermal energy through fluorescence resonance energy transfer (FRET) between T and P, coupling with the original heat energy generated by the photothermal agent P itself, thus resulting in image-guided dual PTT. The photothermal conversion efficiency of DTPR reached 60.3% (dual PTT), much higher as compared to its inherent photothermal effect of only 31.5% (single PTT), which was further proved by the more severe photothermal ablation in vitro and in vivo upon 808 nm laser irradiation. Conclusion: Such smart "nanococktail" nanomaterials could be recognized as a promising photothermal nanotheranostics for image-guided cancer treatment.


Giant Helical Dichroism of Single Chiral Nanostructures with Photonic Orbital Angular Momentum.
Optical activity, demonstrating the chiral light-matter interaction, has attracted tremendous attention in both fundamental theoretical research and advanced applications of high-efficiency enantioselective sensing and next-generation chiroptical spectroscopic techniques. However, conventional chiroptical responses are normally limited in large assemblies of chiral materials by circularly polarized light, exhibiting extremely weak chiroptical signals in a single chiral nanostructure. Here, we demonstrate that an alternative chiral freedom of light-orbital angular momentum-can be utilized for generating strong helical dichroism in single chiral nanostructures. The helical dichroism by monochromatic vortex beams can unambiguously distinguish the intrinsic chirality of nanostructures, in an excellent agreement with theoretical predictions. The single planar-chiral nanostructure can exhibit giant helical dichroism of ∼20% at the visible wavelength. The vortex-dependent helical dichroism, expanding to single nanostructures and two-dimensional space, has implications for high-efficiency chiroptical detection of planar-chiral nanostructures in chiral optics and nanophotonic systems.


Impact of document consolidation on healthcare providers' perceived workload and information reconciliation tasks: a mixed methods study.
Information reconciliation is a common yet complex and often time-consuming task performed by healthcare providers. While electronic health record systems can receive "outside information" about a patient in electronic documents, rarely does the computer automate reconciling information about a patient across all documents. Using a mixed methods design, we evaluated an information system designed to reconcile information across multiple electronic documents containing health records for a patient received from a health information exchange (HIE) network. Nine healthcare providers participated in scenario-based sessions in which they manually consolidated information across multiple documents. Accuracy of consolidation was measured along with the time spent completing 3 different reconciliation scenarios with and without support from the information system. Participants also attended an interview about their experience. Perceived workload was evaluated quantitatively using the NASA-TLX tool. Qualitative analysis focused on providers' impression of the system and the challenges faced when reconciling information in practice. While 5 providers made mistakes when trying to manually reconcile information across multiple documents, no participants made a mistake when the system supported their work. Overall perceived workload decreased significantly for scenarios supported by the system (37.2% in referrals, 18.4% in medications, and 31.5% in problems scenarios, P < 0.001). Information reconciliation time was reduced significantly when the system supported provider tasks (58.8% in referrals, 38.1% in medications, and 65.1% in problem scenarios). Automating retrieval and reconciliation of information across multiple electronic documents shows promise for reducing healthcare providers' task complexity and workload.


What Is the Prevalence of Cam Deformity After Prophylactic Pinning of the Contralateral Asymptomatic Hip in Unilateral Slipped Capital Femoral Epiphysis? A 10-year Minimum Followup Study.
Prophylactic pinning of the asymptomatic and normal-appearing contralateral hip in patients with unilateral slipped capital femoral epiphysis (SCFE) remains controversial. Understanding the minimal 10-year clinical, functional, and radiographic outcomes of the contralateral asymptomatic hip in unilateral SCFE may be helpful in the decision regarding whether the benefits associated with potentially preventing a SCFE are outweighed by the risk of additional surgery. Among patients with SCFE treated with prophylactic pinning of the asymptomatic and contralateral hip, we sought (1) to determine the complications and reoperations; (2) to evaluate the development of cam deformities and the frequency and severity of osteoarthritis progression; and (3) to characterize hip pain and function as measured by the Harris hip score (HHS) and the Hip Disability and Osteoarthritis Outcome Score (HOOS) at minimal 10-year followup. Between 1998 and 2005 all patients with SCFE seen at our institution were treated with the modified Dunn procedure and all were offered prophylactic pinning of the contralateral asymptomatic hip. Of the 41 patients who underwent the unilateral modified Dunn procedure and who had an asymptomatic contralateral hip, 37 patients (90%) underwent pinning of that contralateral hip. Of those, 33 patients (80%) were available for clinical and radiographic evaluation for this retrospective study at a minimum of 10 years (mean followup 12 ± 2 years) after surgery. Three patients of the 37 patients only had 10-year clinical followup, including questionnaires sent by mail and telephone, because they refused further radiographic followup and one patient was lost to followup. The group included 19 males and 17 females whose age at surgery was a mean of 13 ± 2 years. Medical charts were reviewed and patients were asked about complications and additional surgical procedures. Most recent postoperative radiographs were evaluated for measurement of the alpha angle, head-neck offset, epiphysis orientation, and osteoarthritis grading according to Tönnis classification and minimum joint space width. The presence of a cam deformity was defined by an alpha angle measurement > 60° on the AP radiograph and/or > 55° on the lateral radiograph. Hip function and pain were assessed by the HHS and HOOS outcome measures. No complications with prophylactic in situ pinning were recorded. Four of 36 (11%) patients underwent subsequent surgical treatment for cam-type femoroacetabular impingement (FAI), and hardware removal was performed in four hips (11%). The mean alpha angle was 53° ± 8° on the AP radiograph and 49° ± 8° on the lateral view at followup. In total, 10 of 33 hips (30%) had a cam morphology at the femoral head-neck junction and four (12%) were symptomatic and underwent FAI surgery. Six of 33 patients (18%) developed an asymptomatic cam morphology at the femoral head-neck junction; in three of 33 hips (9%), the cam deformity instead of lesion were visible only on the lateral projection, and 9% were visible on both the AP and lateral projections. The preoperative offset of the femoral head-neck junction was 10 ± 3 mm on the AP view and 11 ± 4 mm on the lateral view. At followup, the AP offset was 7 ± 3 mm and the lateral offset was 6 ± 3 mm, and on the lateral view, the offset was < 10 mm in eight hips (22%). No patient had radiographic signs of hip osteoarthritis (Tönnis Grade 0). The mean minimum joint space width was 4 ± 0.4 mm. The mean HHS for the 32 patients who did not undergo subsequent surgery was 97 ± 5 at latest followup. The mean postoperative HOOS was 94 ± 8 for the 32 patients at latest followup. At a minimum followup of 10 years after prophylactic pinning of a contralateral asymptomatic hip, most patients achieve excellent hip scores; however, a substantial proportion will develop a symptomatic cam deformity despite prophylactic pinning. No patient had signs of osteoarthritis at a minimum of 10 years, but almost one-third of the patients who underwent prophylactic pinning developed a cam deformity. Level IV, therapeutic study.


Genetics of factors affecting the life history of Drosophila melanogaster. I. Female productivity.
Starting from four basic strains of Drosophila melanogaster, two laboratory strains (cn bw, Tokyo) and two isofemale lines (B-102, B-103) originated from a wild population in Texas, we constructed by repeated backcrosses through females for 20 or more generations a total of 16 strains of all possible combinations between the chromosome sets and cytoplasmic classes. Females from these 16 synthesized strains were then examined for their reproductive performance during their entire life span.---The chromosome set from the cn bw strain was found to associate with the highest female productivity when the age of females was very young, but these females ceased their reproduction and died relatively earlier, resulting in a smaller number of total progeny. The B-102 and B-103 chromosome sets, on the other hand, were associated with the lowest productivity when the females were young, but they lived and continued reproduction longer, resulting in a larger number of total progeny. The Tokyo chromosome set was associated with female productivity intermediate between the other two groups.---Cytoplasmic factors were found to affect the productivity of young females, with the cytoplasm from the cn bw strain associated with the highest productivity. Longevity was not cytoplasmically affected.---There was a clear interaction in female productivity between the Tokyo chromosome set and the cytoplasm from the Texas isofemale lines; the lifetime female productivity, as well as longevity, associated with the Tokyo chromosome set was found to increase considerably when it was substituted into the cytoplasm of the Texas isofemale lines. This chromosome-cytoplasm interaction appeared to be independent of the two systems of hybrid dysgenesis.


Characterization of a supernumerary small marker X chromosome in two females with similar phenotypes.
We describe two female patients mosaic for a cell line with an extra marker X chromosome in addition to a normal 46,XX cell line. To our knowledge, these cases are the first reports of females who had a cell line with a supernumerary marker X chromosome in addition to a normal cell line. They also had strikingly similar manifestations, including small hands and feet, minor facial anomalies, obesity, and mental retardation. The DNA content of the mar(X) chromosomes was investigated by fluorescent in situ hybridization using pericentromeric probes. The XIST gene, which is necessary for initiation of X-inactivation, was deleted from both marker chromosomes, suggesting that these chromosomes were not subject to inactivation. The short arm breakpoints of the mar(X)s were between the DNA markers DXS423E on Xp11.21 and UBE1 on Xp11.23. In Patient 1, mar(X) contained the androgen receptor gene and the DNA marker DXS1, both mapping to Xq11.2, whereas in Patient 2 the chromosome breakpoint was proximal to these markers. We suggest that the similar phenotypes of these patients may be due to the overexpression of genes in the common pericentromeric region of the X chromosome.


Yeast two-hybrid identification of prostatic proteins interacting with human sex hormone-binding globulin.
Yeast two-hybrid (Y2H) screening of a prostate cDNA library with the cDNA for sex hormone-binding globulin (SHBG) has been used to identify proteins through which SHBG may exert autocrine or paracrine effects on sex steroid target tissues. The library screen gave 230 positive interactions of which around 60 have been sequenced. Of the proteins identified to date from database (BLAST) searches of these sequences, SHBG is one of those occurring most frequently. Amongst the proteins of interest are the membrane-associated proteins flotillin-1 and PRV-1, the enzymes cathepsin D, kallikrein 4 and acid phosphatase, various metallothioneins and translation elongation factor 1 alpha. The significance of the interaction of SHBG with these proteins is discussed.


Ventilator-associated pneumonia in a multi-hospital system: differences in microbiology by location.
To determine whether there were differences in the microbiologic etiologies of ventilator-associated pneumonia in different clinical settings. Observational retrospective cohort study of microbiologic etiologies of ventilator-associated pneumonia from 1998 to 2001 in a multi-hospital system. Microbiologic results were compared between hospitals and between different intensive care units (ICUs) within hospitals. Three hospitals--one pediatric teaching hospital, one adult teaching hospital, and one community hospital--in one healthcare system in the midwestern United States. Patients at the target hospitals who developed ventilator-associated pneumonia and for whom microbiologic data were available. Seven hundred fifty-three episodes of ventilator-associated pneumonia had culture data available for review. The most common organisms at all hospitals were Staphylococcus aureus (28.4%) and Pseudomonas aeruginosa (25.2%). The pediatric hospital had higher proportions of Escherichia coli (9.5% vs 2.3%; P < .001) and Klebsiella pneumoniae (13% vs 3.1%; P < .001) than did the adult hospitals. In the pediatric hospital, the pediatric ICU had higher P aeruginosa rates than did the neonatal ICU (33.3% vs 17%; P = .01). In the adult hospitals, the surgical ICU had higher Acinetobacter baumannii rates (10.2% vs. 1.7%; P < .001) than did the other ICUs. Microbiologic etiologies of ventilator-associated pneumonia vary between and within hospitals. Knowledge of these differences can improve selection of initial antimicrobial regimens, which may decrease mortality.


Utilizing magnetic xanthan gum nanocatalyst for the synthesis of acridindion derivatives via functionalized macrocycle Thiacalix[4]arene.
An effective method for synthesizing acridinedione derivatives using a xanthan gum (XG), Thiacalix[4]arene (TC4A), and iron oxide nanoparticles (IONP) have been employed to construct a stable composition, which is named Thiacalix[4]arene-Xanthan Gum@ Iron Oxide Nanoparticles (TC4A-XG@IONP). The process used to fabricate this nanocatalyst includes the in-situ magnetization of XG, its amine modification by APTES to get NH2-XG@IONP hydrogel, the synthesis of TC4A, its functionalization with epichlorohydrine, and eventually its covalent attachment onto the NH2-XG@IONP hydrogel. The structure of the TC4A-XG@IONP was characterized by different analytical methods including Fourier-transform infrared spectroscopy, X-Ray diffraction analysis (XRD), Energy Dispersive X-Ray, Thermal Gravimetry analysis, Brunauer-Emmett-Teller, Field Emission Scanning Electron Microscope and Vibration Sample Magnetomete. With magnetic saturation of 9.10 emu g-1 and ~ 73% char yields, the TC4As-XG@IONP catalytic system demonstrated superparamagnetic property and high thermal stability. The magnetic properties of the TC4A-XG@IONP nanocatalyst system imparted by IONP enable it to be conveniently isolated from the reaction mixture by using an external magnet. In the XRD pattern of the TC4As-XG@IONP nanocatalyst, characteristic peaks were observed. This nanocatalyst is used as an eco-friendly, heterogeneous, and green magnetic catalyst in the synthesis of acridinedione derivatives through the one-pot pseudo-four component reaction of dimedone, various aromatic aldehydes, and ammonium acetate or aniline/substituted aniline. A combination of 10 mg of catalyst (TC4A-XG@IONP), 2 mmol of dimedone, and 1 mmol of aldehyde at 80 °C in a ethanol at 25 mL round bottom flask, the greatest output of acridinedione was 92% in 20 min.This can be attributed to using TC4A-XG@IONP catalyst with several merits as follows: high porosity (pore volume 0.038 cm3 g-1 and Pore size 9.309 nm), large surface area (17.306 m2 g-1), three dimensional structures, and many catalytic sites to active the reactants. Additionally, the presented catalyst could be reused at least four times (92-71%) with little activity loss, suggesting its excellent stability in this multicomponent reaction. Nanocatalysts based on natural biopolymers in combination with magnetic nanoparticles and macrocycles may open up new horizons for researchers in the field.


Beyond androgen deprivation: ancillary integrative strategies for targeting the androgen receptor addiction of prostate cancer.
The large majority of clinical prostate cancers remain dependent on androgen receptor (AR) activity for proliferation even as they lose their responsiveness to androgen deprivation or antagonism. AR activity can be maintained in these circumstances by increased AR synthesis--often reflecting increased NF-κB activation; upregulation of signaling pathways that promote AR activity in the absence of androgens; and by emergence of AR mutations or splice variants lacking the ligand-binding domain, which render the AR constitutively active. Drugs targeting the N-terminal transactivating domain of the AR, some of which are now in preclinical development, can be expected to inhibit the activity not only of unmutated ARs but also of the mutant forms and splice variants selected for by androgen deprivation. Concurrent measures that suppress AR synthesis or boost AR turnover could be expected to complement the efficacy of such drugs. A number of nutraceuticals that show efficacy in prostate cancer xenograft models--including polyphenols from pomegranate, grape seed, and green tea, the crucifera metabolite diindolylmethane, and the hormone melatonin--have the potential to suppress AR synthesis via downregulation of NF-κB activity; clinical doses of salicylate may have analogous efficacy. The proteasomal turnover of the AR is abetted by diets with a high ratio of long-chain omega-3 to omega-6 fatty acids, which are beneficial in prostate cancer xenograft models; berberine and sulforaphane, by inhibiting AR's interaction with its chaperone Hsp90, likewise promote AR proteasomal degradation and retard growth of human prostate cancer in nude mice. Hinge region acetylation of the AR is required for optimal transactivational activity, and low micromolar concentrations of the catechin epigallocatechin-3-gallate (EGCG) can inhibit such acetylation--possibly explaining the ability of EGCG administration to suppress androgenic activity and cell proliferation in prostate cancer xenografts. Hence, it is proposed that regimens featuring an N-terminal domain-targeting drug, various nutraceuticals/drugs that downregulate NF-κB activity, and/or supplemental intakes of fish oil, berberine, sulforaphane, and EGCG have potential for blocking proliferation of prostate cancer by targeting its characteristic addiction to androgen receptor activity.


Cyclization of peptides on a solid support. Application to cyclic analogs of substance P.
The general conditions for cyclization of peptides on polymer matrix by disulfide bridge formation are reported. This procedure is based on attack of 3-nitro-2-pyridinesulfenyl group (Npys) by a thiol function. It has been used for synthesis of five cyclic analogs of Substance P.


A Listening Tour: Conversations about Obamacare across America's Heartland.
During my sabbatical, I rode my bike 3300 miles from Washington, DC, to Seattle, WA, in order to engage in dialog with people along the northern tier of America's heartland. Through informal and candid conversations with >100 people, I gained insights into attitudes and opinions about the Patient Protection and Affordable Care Act (Obamacare). The comments were overwhelmingly negative. In this reflective essay, I share some of the conversations I had and the insights I gained from this remarkable journey across our beautiful country.


Construction of a field trap for initiating an ovipositional response in Aedes taeniorhynchus.
An oviposition trap was constructed for the black saltmarsh mosquito, Aedes taeniorhynchus. The trap consisted of a 50 x 60-cm piece of contaminated 100% cotton bath towel, saturated with 85% tap water, a container, and a cover of dried plant parts placed over the contaminated toweling. This combination initiated oviposition. Contamination of the toweling was due to populations of bacteria and fungi. The eggs recovered were free from soil and debris.


Microwave-assisted extraction followed by CE for determination of catechin and epicatechin in green tea.
In this work, for the first time, microwave-assisted extraction (MAE) followed by CE was developed for the fast analysis of catechin and epicatechin in green tea. In the proposed method, catechin and epicatechin in green tea samples were rapidly extracted by MAE technique, and then analyzed by CE. The MAE conditions and the method's validation were studied. It is found that the extraction time of 1 min with 400 W microwave irradiation is enough to completely extract catechin and epicatechin in green tea sample, whereas the conventional ultrasonic extraction (USE) technique needs long extraction time of 60 min. The method validations were also studied in this work. The calibration curve shows good linearity in 0.01-3 mg/mL for catechin (R(2)=0.993), and 0.005-3 mg/mL for epicatechin (R(2)=0.996), respectively. The RSD values for catechin and epicatechin are 0.65 and 2.58%, respectively. This shows that the proposed method has good reproducibility. The proposed method has good recoveries, which are 118% for catechin and 120% for epicatechin. The proposed method was successfully applied to determination of the catechin and epicatechin in different green tea samples. The experiment results have demonstrated that the MAE following CE is a simple, fast and reliable method for the determination of catechin and epicatechin in green tea.


Greater fetal crown-rump length growth with the use of in vitro fertilization or intracytoplasmic sperm injection conceptions after thawed versus fresh blastocyst transfers: secondary analysis of a prospective cohort study.
To compare first-trimester fetal crown-rump length (CRL) measurements in pregnancies obtained after thawed blastocyst transfer versus fresh blastocyst transfer after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Prospective longitudinal cohort study of CRL Z scores with adjustment for major confounders. University-affiliated obstetrics, fetal medicine, and fertility units. Singleton gestations conceived via IVF/ICSI and fresh or thawed blastocyst transfer with ultrasound performed at 6-14 weeks of gestational age. None. CRL Z scores. A total of 365 IVF/ICSI pregnancies were recruited (fresh: 161; thawed: 204). The mean CRL Z score at 6-14 weeks was significantly greater in thawed versus fresh transfers. Different growth trajectories between thawed and fresh transfers were detected: Mean CRL Z score was 0 at 65 days in fresh versus 80 days in frozen. Comparisons of both fresh and thawed transfers with reference values from the general population confirmed significantly lower CRL Z scores in both IVF/ICSI groups (P<.001). The risks of CRL <5th percentile in fresh versus thawed were, respectively 68% vs. 40% at 6 weeks and 2% vs. 1% at 14 weeks. A significant positive correlation between CRL Z scores and birth weight Z scores was found only for fresh transfers, not for thawed. At 6-14 weeks, thawed blastocyst transfers after IVF/ICSI conceptions present greater CRLs compared with fresh, and both IVF/ICSI groups show smaller CRLs than the general population. This effect is particularly evident before 9 weeks and it may favor birth weight difference of thawed versus fresh BT pregnancies.


Multiphoton fabrication of chemically responsive protein hydrogels for microactuation.
We report a method for creating stimuli-responsive biomaterials in which scanning nonlinear excitation is used to photocrosslink proteins at submicrometer 3D coordinates. Proteins with differing hydration properties can be combined to achieve tunable volume changes that are rapid and reversible in response to changes in chemical environment. Protein matrices having arbitrary 3D topographies and definable density gradients over micrometer dimensions provide the ability to effect rapid (<1 sec) and precise mechanical manipulations by means of changes in hydrogel size and shape, and applicability of these materials to cell biology is shown through the fabrication of responsive bacterial cages.


Tissue adhesives in otorhinolaryngology.
The development of medical tissue adhesives has a long history without finding an all-purpose tissue adhesive for clinical daily routine. This is caused by the specific demands which are made on a tissue adhesive, and the different areas of application. In otorhinolaryngology, on the one hand, this is the mucosal environment as well as the application on bones, cartilage and periphery nerves. On the other hand, there are stressed regions (skin, oral cavity, pharynx, oesophagus, trachea) and unstressed regions (middle ear, nose and paranasal sinuses, cranial bones). But due to the facts that adhesives can have considerable advantages in assuring surgery results, prevention of complications and so reduction of medical costs/treatment expenses, the search for new adhesives for use in otorhinolaryngology will be continued intensively. In parallel, appropriate application systems have to be developed for microscopic and endoscopic use.


Sexual health in adult men with spina bifida.
Medical and surgical advances in the treatment of spina bifida (SB) have resulted in increasing numbers of patients reaching adulthood. As such, issues related to sexual maturity are being investigated to offer optimal healthcare to men with spina bifida. This report constitutes a review of the current literature relating to adults with spina bifida and issues of sexuality, erectile dysfunction and fertility. In general, adult males with spina bifida have normal sexual desires and an interest in addressing these issues with healthcare providers. Sexual education and access to intimacy are delayed compared to the general population. 75% of men achieve erections, but maintaining erections is a problem and some may be merely reflexive in nature. The many of these men show marked improvement with sildenafil. In SB erectile dysfunction and infertility are related to the level of neurological lesion with the best performance status in those with sacral lesions and intact reflexes. Men with lesions higher than T10 are at risk for azoospermia. There is an increased risk of neural tube defects in the children of men with spina bifida, but the current incidence with modern folic acid therapy is unknown. As the number of males with spina bifida reaching sexual maturity increases, further investigation into sexuality, sex education, intimacy, and treatments for erectile dysfunction and infertility will be needed.


NO2 decreases paracellular resistance to ion and solute flow in alveolar epithelial monolayers.
Primary cultured monolayers of rat alveolar epithelial cells grown on tissue culture-treated Nuclepore filters were exposed to 2.5 ppm nitrogen dioxide (NO2) for 2-20 min. Changes in monolayer bioelectric properties and solute permeabilities were subsequently measured. Exposure to NO2 produced a dose-dependent decrease in monolayer transepithelial electrical resistance (Rt), whereas monolayer short-circuit current was unaffected. Post-exposure monolayer permeability to 14C-sucrose (which primarily crosses alveolar epithelium via the paracellular pathway) increased markedly. That for 3H-glycerol (which permeates through both paracellular and transcellular pathways) increased to a lesser extent. Partial recovery of Rt and solute permeabilities was noted by 48-h post-exposure. The time courses of the decrease in Rt and increase in solute permeabilities were similar. These results suggest that NO2 primarily impairs passive alveolar epithelial barrier functions in vitro, probably by altering intercellular junctions, and does not appear to directly affect cell membrane active ion transport processes. When correlated with results obtained from experimental approaches, studies of in vitro alveolar epithelial monolayers may facilitate investigations of dosimetry, sites, and mechanisms of oxidant injury in the lung.


A proposed field emergency donor panel questionnaire and triage tool.
The provision of transfusion support to isolated military or civilian projects may require the use of an emergency donor panel (EDP) for immediate warm fresh whole blood (WFWB). The aim of this short discussion article is to raise and resolve some of the practical aspects for the nonspecialist faced with the emergency collection of WFWB whole blood in the austere medical environment (AME). A proposed field EDP questionnaire and triage tool (QTT) is presented. It is designed for the hostile, remote, or austere environment that falls outside normal regulated supply of cold-stored blood products or removed from trained blood collection personnel, where collection may fall to an isolated medical provider. The tool has been drafted based on review of existing guidelines and consultation with practitioners. It serves as a point of reference for local guidelines and has yet to be validated. The use of the EDP is associated with risk; however, it remains the simplest method of providing rapid transfusion support. The best way to manage the risk is to brief and prescreen blood donors before deployment. An abbreviated donor QTT can be an aide to decision making at the time of donation. The tool should be tailored to requirements and underpinned by policy and training.


Hyponatraemia associated rhabdomyolysis following water intoxication.
A young man with bipolar disorder was admitted in a coma. Cerebral oedema secondary to severe hyponatraemia was implicated. This was due to self-induced water intoxication. He developed rhabdomyolysis, a massive creatine kinase (out of proportion to longstanding antipsychotic medication) and acute renal failure. In the intensive care unit, hyponatraemia was corrected, and following appropriate fluid resuscitation, with forced alkaline diuresis, the rhabdomyolysis and renal function normalised, averting renal support. While a full recovery ensued, the persisting risk factors for hyponatraemia, that is polydipsia, and its association with rhabdomyolysis, increased the chances of a recurrence. Closely supervised regulation of his water intake, and monitoring of antipsychotic efficacy (for biochemical homeostatsis) are essential for secondary prevention. Rhabdomyolysis is a rare complication of hyponatraemia. When associated with psychogenic polydipsia, the acute and chronic management are challenging. Vaptans, which are aquaretics, that preferentially prevent renal tubular water reabsorption, may be beneficial in this situation.


Asymptotic softness of a laterally confined sheet in a pressurized chamber.
Elastohydrodynamic models, that describe the interaction between a thin sheet and a fluid medium, have been proven successful in explaining the complex behavior of biological systems and artificial materials. Motivated by these applications we study the quasistatic deformation of a thin sheet that is confined between the two sides of a closed chamber. The two parts of the chamber, above and below the sheet, are filled with an ideal gas. We show that the system is governed by two dimensionless parameters, Δ and η, that account respectively for the lateral compression of the sheet and the ratio between the amount of fluid filling each part of the chamber and the bending stiffness of the sheet. When η≪1 the bending energy of the sheet dominates the system, the pressure drop between the two sides of the chamber increases, and the sheet exhibits a symmetric configuration. When η≫1 the energy of the fluid dominates the system, the pressure drop vanishes, and the sheet exhibits an asymmetric configuration. The transition between these two limiting scenarios is governed by a third branch of solutions that is characterized by a rapid decrease of the pressure drop. Notably, across the transition the energetic gap between the symmetric and asymmetric states scales as δE∼Δ^{2}. Therefore, in the limit Δ≪1 small variations in the energy are accompanied by relatively large changes in the elastic shape.


[Infectious spondylodiskitis and epidural abscess after spinal puncture for pilonidal sinus excision].
Vertebral infections after spinal puncture are rare and often inadequately documented. Their incidence does not exceed that of spontaneous epidural abscesses and we should therefore be cautious about assuming a causal relation between puncture and an abscess. After analyzing 10 published cases we saw that only half of them reported on aseptic conditions and only 2 patients seem to have had a prior infection. In 3 cases, the abscesses appeared after technically simple punctures whereas half the reports did not even mention the type of puncture. This complication should be considered whenever a patient develops back pain and fever, even if there are no neurological deficits and even after a simple spinal puncture. Given that early diagnosis and treatment have proven effective in improving the survival rate and reducing the rate of neurological sequelae, magnetic resonance images should be ordered urgently so that early treatment can be established.


Protective effects of different exercise modalities in an Alzheimer's disease-like model.
Our aim was to investigate the probable protective effects of aerobic, resistance and combined exercise methods on ovariectomy and d-galactose induced Alzheimer's Disease (AD)-like model. d-galactose (100mg/kg) or saline were administered intraperitoneally for 6 weeks to ovariectomized or sham-operated rats (n=8/group). Aerobic (AE), resistance (RE) and combined exercises (CE) (aerobic+resistance) were performed for 3 times a week for 6 weeks. Anxiety level and cognitive functions were evaluated via hole-board and object recognition tests. Brain myeloperoxidase, malondialdehyde, nitric oxide activity, lucigenin-enhanced chemiluminescence, glutathione and serum insulin like growth factor-I (IGF-I) assays were done. Hippocampal mRNA levels of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and amyloid precursor protein 695 (APP695) were measured. Amyloid Beta (Aβ), NGF, BDNF, IGF-I immunoreactive neurons were evaluated. Freezing time were increased in AD-like model and decreased back with AE (p<0.05). Deteriorated working memory in AD-like model was improved with all exercise types (p<0.05-0.001). Reduced glutathione levels in AD-like model were increased and increased malondialdehyde levels were reduced and serum IGF-I levels were increased by all exercises (p<0.05-0.001). Increased APP mRNA levels in AD-like model were decreased via CE (p<0.05). Elevated Aβ scores in AD-like model were decreased by RE and CE (p<0.01) in hippocampus and by all exercise types in cortex (p<0.05-0.01). Decreased cortical NGF immunocytochemical scores of AD-like model were increased by CE (p<0.05). Different exercise models may have protective effects in development stage of AD via reducing oxidative stress and Aβ scores, and by improving antioxidant system and brain plasticity.


Management of ventricular electrical storm: a contemporary appraisal.
Ventricular electrical storm (VES) is a clinical scenario characterized by the clustering of multiple episodes of sustained ventricular arrhythmias (VA) over a short duration. Patients with VES are prone to psychological disorders, heart failure decompensation, and increased mortality. Studies have shown that 10-28% of the patients with secondary prevention ICDs can sustain VES. The triad of a susceptible electrophysiologic substrate, triggers, and autonomic dysregulation govern the pathogenesis of VES. The rate of VA, underlying ventricular function, and the presence of implantable cardioverter-defibrillator (ICD) determine the clinical presentation. A multi-faceted approach is often required for management consisting of acute hemodynamic stabilization, ICD reprogramming when appropriate, antiarrhythmic drug therapy, and sedation. Some patients may be eligible for catheter ablation, and autonomic modulation with thoracic epidural anesthesia, stellate ganglion block, or cardiac sympathetic denervation. Hemodynamically unstable patients may benefit from the use of left ventricular assist devices, and extracorporeal membrane oxygenation. Special scenarios such as idiopathic ventricular fibrillation, Brugada syndrome, Long and short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy, and cardiac sarcoidosis have been described as well. VES is a cardiac emergency that requires swift intervention. It is associated with poor short and long-term outcomes. A structured team-based management approach is paramount for the safe and effective treatment of this sick cohort.


Effects of impending ovarian failure induced by 4-vinylcyclohexene diepoxide on fertility in C57BL/6 female mice.
Repeated daily dosing of mice with 4-vinylcyclohexene diepoxide (VCD) causes a gradual onset of ovarian failure, providing a model for perimenopause. Because increasing numbers of women are delaying starting a family, infertility in aging women is of concern. This study was designed to determine the effects of impending ovarian failure on fertility in VCD-treated mice. Female C57BL/6J mice were dosed daily (17 d) with vehicle control or VCD (160 mg/kg, intraperitoneally) to deplete primordial follicles and then were divided into 2 groups. Group 1 was mated soon after dosing; group 2 was mated on day 20 after dosing, during impending ovarian failure. Fertility was evaluated on gestational day 16. In group 1, cycle length, pregnancy rate, and number of live fetuses did not differ between VCD-treated animals and controls, but VCD-treated mice required more matings to become pregnant and had more resorptions. In group 2, VCD-treated mice demonstrated proestrus and copulatory plugs, but only 1 animal became pregnant, and she had no viable fetuses. Ovaries from pregnant and nonpregnant controls contained similar numbers of follicles and corpora lutea. Ovaries from VCD-treated animals contained no follicles, and corpora lutea were seen only in pregnant animals. In VCD-treated mice mated soon after dosing, conception was more difficult and more resorbed fetuses were seen, whereas in those mated closer to impending ovarian failure, no successful pregnancies were achieved. These results demonstrate that VCD-treated mice can be used to model infertility in perimenopausal women.


Protein tyrosine nitration in pea roots during development and senescence.
Protein tyrosine nitration is a post-translational modification mediated by reactive nitrogen species (RNS) that is associated with nitro-oxidative damage. No information about this process is available in relation to higher plants during development and senescence. Using pea plants at different developmental stages (ranging from 8 to 71 days), tyrosine nitration in the main organs (roots, stems, leaves, flowers, and fruits) was analysed using immunological and proteomic approaches. In the roots of 71-day-old senescent plants, nitroproteome analysis enabled the identification a total of 16 nitrotyrosine-immunopositive proteins. Among the proteins identified, NADP-isocitrate dehydrogenase (ICDH), an enzyme involved in the carbon and nitrogen metabolism, redox regulation, and responses to oxidative stress, was selected to evaluate the effect of nitration. NADP-ICDH activity fell by 75% during senescence. Analysis showed that peroxynitrite inhibits recombinant cytosolic NADP-ICDH activity through a process of nitration. Of the 12 tyrosines present in this enzyme, mass spectrometric analysis of nitrated recombinant cytosolic NADP-ICDH enabled this study to identify the Tyr392 as exclusively nitrated by peroxynitrite. The data as a whole reveal that protein tyrosine nitration is a nitric oxide-derived PTM prevalent throughout root development and intensifies during senescence.


Circannual rhythm of free fatty acids and diacylglycerols in 5-day-old rat cerebrum during pentylenetetrazol-induced convulsions.
Free fatty acids (FFA) and diacylglycerol (DG) content and composition in the cerebrum of 5-day-old rats were studied after pentylenetetrazol (PTZ)-induced convulsions. A threefold increase in brain FFA was observed 30 min after PTZ injection in experiments carried out in spring. In contrast, a 50% decrease in FFA content was observed during summer. These changes were accounted for by saturated and monoenoic fatty acids, whereas arachidonic and docosahexaenoic acids were not affected during the convulsive episode in either season. The effect of PTZ on brain DG was much smaller than it was on FFA, and less sensitive to seasonal influence. However, DG released in the summer was significantly less enriched in arachidonic acid than in the spring. Levels of FFA and DG in untreated animals were found to be subject to a circannual rhythm. Both the levels of FFA and their degree of unsaturation (unsaturated fatty acids/total FFA) were highest in summer and lowest in winter, whereas the opposite was true for DG. Circannual variations in these metabolites may be the manifestation of a programmed biological calendar regulating enzymes of brain lipid metabolism in homeotherms that under natural conditions must adapt to changing environmental temperatures.


The copy number variation landscape of congenital anomalies of the kidney and urinary tract.
Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.


Ellipsometry of Colloidal Solutions: New Experimental Setup and Application to Metallic Colloids.
An ellipsometric cell is developed to simultaneously determine the shape distribution, the volume fraction, and the complex refractive index of gold and silver colloids. Simulation reveals that this cell drastically improves the detection limit of ellipsometry. Indeed, Ag and Au nanoparticles (NPs) are detected at the ppmv level. We demonstrate that the NPs shape distribution can be estimated from ellipsometric measurements by analyzing them with a shape distributed effective medium theory (SDEMT). The obtained distributions from ellipsometry are in agreement with those deduced from transmission electron microcopy (TEM). Contrary to TEM, ellipsometry probes a large number of NPs estimated at about 1011 NPs. Finally, we show that the complex refractive index of colloids as determined from ellipsometry is sensitive to the optical properties of the solvent and the plasmonic properties of NPs.


No consistent evidence for the anti-inflammatory effect of vagus nerve stimulation in humans: A systematic review and meta-analysis.
Vagus nerve stimulation (VNS) has been identified as an innovative immunosuppressive treatment strategy in rodent studies. However, its' clinical potential is still unclear. Therefore, we aimed to assess whether VNS can reduce inflammatory proteins and/or immune cells in humans, through a pre-registered systematic review and meta-analysis according to PRISMA guidelines. The databases Cochrane, Pubmed and World of Knowledge were searched in duplicate up to the 3rd of March 2022 and publications from identified clinical trial registrations were identified until 20th of August 2023. Studies were included if they provided peer-reviewed data for humans who received VNS as short-term (<=1 day) or long-term (>=2 days-365 days) stimulation and reported at least one cytokine or immune cell after treatment.Screening of title, abstract, full text, and data extraction was performed in duplicate by two independent reviewers. Data were pooled using a random-effects model and meta-regression was performed for moderating factors. Reporting bias was assessed. The standardized mean difference (Hedge's g)was used to indicate overall differences of cytokine data (mean and standard deviation or median and interquartile range at the study level) to test our a-priori hypothesis. The systematic review of 34 studies with 1021 participants (305 in a control/sham condition and 716 receiving VNS) revealed anti-inflammatory effects of VNS for cytokines in several reports, albeit often in subgroup analyses, but our meta-analyses of 26 studies did not confirm these findings. Although most cytokines were numerically reduced, the reduction did not reach statistical significance after VNS: not in the between-group comparisons (short-term: TNF-α: g = -0.21, p = 0.359; IL-6: g = -0.94, p = 0.112; long-term: TNF-α: g = -0.13, p = 0.196; IL-6: g = -0.67, p = 0.306).; nor in the within-study designs (short-term: TNF-α: g = -0.45, p = 0.630; IL-6: g = 0.28, p = 0.840; TNF-α: g = -0.53, p = 0.297; IL-6:g = -0.02, p = 0.954). Only the subgroup analyses of 4 long term studies with acute inflammation was significant: VNS decreased CRP significantly more than sham stimulation. Additional subgroup analyses including stimulation duration, stimulation method (invasive/non-invasive), immune stimulation, and study quality did not alter results. However, heterogeneity was high, and most studies had poor to fair quality. Given the low number of studies for each disease, a disease-specific analysis was not possible. In conclusion, while numeric effects were reported in individual studies, the current evidence does not substantiate the claim that VNS impacts inflammatory cytokines in humans. However, it may be beneficial during acute inflammatory events. To assess its full potential, high-quality studies and technological advances are required.


[Cholesterol embolism disease: study of 16 cases].
The cholesterol embolism syndrome is a multisystemic disease resulting from cholesterol crystal embolization to many organs including skin, kidney and CNS. Vascular procedures and anticoagulation have been identified as triggering factors. Sixteen patients were prospectively reviewed diagnosed of cholesterol embolism syndrome from 1991 to 1998. The mean age was 68 years and all had at least two risk factors for atherosclerosis (hypertension, smoking, diabetes mellitus, hyperlipemia) as well as pre-existing symptomatic atherosclerotic disease. At least one precipitating factor was identified in 14 patients (heparin in 7, coumarins in 4 and vascular procedure in 7). In six patients two or more triggering factors coexisted. Clinically, 12 patients had livedo reticularis, 10 purpuric lesions, 12 purple toes and 4 painful ulcerations. As a result of progressive gangrene 4 patients required amputation of a portion of the lower extremity. The skin biopsy was diagnostic of cholesterol embolism syndrome in 10 cases and was highly suggestive in the remaining cases. Eleven patients developed renal failure but only five required subsequent dialysis. A cerebrovascular accident was reported in two patients and gastrointestinal bleeding occurred in another three patients. Four patients died but only two as a direct result of the disease. The diagnosis of cholesterol embolisms should be considered among elderly patients, with underlying atherosclerotic disease, who develop typical cutaneous manifestations, hypertension, and renal failure in association with precipitating factors. Given the serious implications of this syndrome, a heightened awareness and preventive measures in the population at risk are essential.


C5a-induced tracheal contraction: effect of an SRS-A antagonist and inhibitors of arachidonate metabolism.
C5a, a peptide derived from the fifth component of complement, has been shown to cause significant prolonged smooth muscle contraction in isolated guinea pig trachea. This contraction was not affected by the antihistamine diphenyhydramine. To assess further the potential role that C5a may play in allergic bronchospasm, we investigated the role of products of arachidonate metabolism in the C5a-induced tracheal contraction. 5,8,11,14-Eicosatetraynoic acid, an inhibitor of lipoxygenase and cyclooxygenase, virtually eliminated the tracheal contraction induced by C5a. The prostaglandin synthesis inhibitor, acetylsalicylate, did not inhibit the C5a-induced tracheal contraction and enhanced the tracheal response to acetylcholine. FPL 55712, an antagonist of slow reacting substance of anaphylaxis (SRS-A), almost completely inhibited the tracheal response to C5a and at higher concentrations employed, FPL 55712 also inhibited the tracheal response to exogenous prostaglandin F 2 alpha. These studies indicate that C5a-induced tracheal contraction is mediated by a product or products of arachidonate metabolism, and is, at least in part, mediated by SRS-A.