Giving back to donor families: the "thank you letter" package insert project.
Family members of organ donors receive anonymous information about the transplant recipients. Also, they often receive written communication from the recipients themselves and or the recipient's family members, expressing gratitude for the generous gifts they donated. The feedback received by donor families serves to affirm that their altruistic decision to donate life-saving and life-enhancing gifts has saved or dramatically improved the lives of the recipients. Feedback allows donor families to assign meaning to the donation itself and make some sense of otherwise tragic circumstances. In contrast, family members of bone and soft tissue donors historically have not received the same level of feedback provided to the family members of organ donors. The tissue banking community, as an extension of the procurement community that provides care to tissue donor families, is in a unique position to facilitate meaningful feedback between bone and soft tissue donor families and their recipients. This article explores the use of tissue packaging as a communication portal to solicit and facilitate the needed feedback loop between bone and soft tissue donor families and their recipients.


Cyproterone acetate reduced antler growth in surgically castrated fallow deer.
We studied the role of androgens in antler growth. In particular, we investigated whether the onset of antler regrowth is triggered by a short-term pulse of testosterone and if low levels of androgens are required for antler growth. The study was conducted on 12 surgically castrated fallow deer bucks (Dama dama) aged approximately 27 months. Six animals (CA group) were given the antiandrogen, cyproterone acetate (CA, 1000 mg/treatment); the others were given vehicle solution only (control). Before each CA treatment, blood was sampled and analysed for testosterone, androstenedione, IGF-1, cortisol, FSH, and LH. CA treatment and blood sampling were performed 2 days before castration, on the day of castration and afterwards at 2-day intervals until day 22. Subsequently, CA treatment and blood sampling continued at weekly intervals until day 270. All animals cast their antlers, followed by antler regrowth in all control bucks, but in only four of the six CA-treated castrates. Plasma testosterone concentrations were low in all animals (between 0.01 and 0.20 ng/ml), but were significantly (P<0001) greater in the controls. In both groups, a temporary increase in testosterone values was recorded around the time of antler regrowth, the peak being significantly (P<0.01) higher in the controls. Androstenedione showed a similar pattern as testosterone. Plasma IGF-1 concentrations increased sharply during the antler growth spurt and did not differ significantly between the two groups throughout the study period. Cortisol concentrations were greater in controls than in the CA group. However, no link with the antler cycle was apparent. FSH and LH concentrations were higher in the controls for most of the study. Antlers produced by the control bucks were significantly larger than those in the CA group (P<0.03). For antler length, testosterone, androstenedione and IGF-1, areas under the curve (AUC) were calculated over the period of antler growth. For the pooled deer (n=12) significant correlations existed between AUCs of antler length and testosterone, but not for antler length and IGF-1. Also, a trend for a positive correlation between AUCs of antler length and androstenedione was noted. It is concluded that a plasma androgen concentration at least above a minimal threshold level is a necessary prerequisite for normal antler regrowth in fallow deer, and that this androgen effect is not mediated via circulating IGF-1. The biological role of low levels of androgens may be to sensitize antler cells to the stimulating effect of IGF.


A New Sythetic Hybrid (A1D5) between Gossypium herbaceum and G. raimondii and Its Morphological, Cytogenetic, Molecular Characterization.
The diploid species G. herbaceum (A1) and G. raimondii (D5) are the progenitors of allotetraploid cotton, respectively. However, hybrids between G. herbaceum and G. raimondii haven't been reported. In the present study, hybridization between G. herbaceum and G. raimondii was explored. Morphological, cytogenetic and molecular analyses were used to assess the hybridity. The interspecific hybrid plants were successfully obtained. Most of the morphological characteristics of the hybrids were intermediate between G. herbaceum and G. raimondii. However, the color of glands, anther cases, pollen and corolla, and the state of bracteoles in hybrids were associated with the G. herbaceum. The color of staminal columns and filaments in hybrids were associated with G. raimondii. Cytogenetic analysis confirmed abnormal meiotic behavior existed in hybrids. The hybrids couldn't produce boll-set. Simple sequence repeat results found that besides the fragments inherited from the two parents, some novel bands were amplified in hybrids, indicating that potential mutations and chromosomal recombination occurred between parental genomes during hybridization. These results may provide some novel insights in speciation, genome interaction, and evolution of the tetraploid cotton species.


First record of Plethus Hagen (Trichoptera, Hydroptilidae) from Japan, with description of a species.
The tropical and subtropical caddisfly genus Plethus Hagen (Hydroptilidae) is recorded from Japan for the first time. The species, Plethus ukalegon Malicky and Chantaramongkol 2007, originally described from Taiwan, is redescribed based on material from Iriomote-jima and Ishigaki-jima, southern Ryukyu Islands, the southernmost region of Japan. Female and immature stages are newly described and compared with Indonesian congeners. The early instar larva was associated with the adult through mitochondrial DNA sequence comparisons, and is described in the genus Plethus for the first time. Larvae live in fast-flowing waters such as hygropetric zones, rapid streams, and waterfalls. Final instar larvae make flattened cases of silk that they attach tightly on smooth rock surfaces.


Functional analyses of an axonemal inner-arm dynein complex in the bloodstream form of Trypanosoma brucei uncover its essential role in cytokinesis initiation.
The flagellated eukaryote Trypanosoma brucei alternates between the insect vector and the mammalian host and proliferates through an unusual mode of cell division. Cell division requires flagellum motility-generated forces, but flagellum motility exerts distinct effects between different life cycle forms. Motility is required for the final cell abscission of the procyclic form in the insect vector, but is necessary for the initiation of cell division of the bloodstream form in the mammalian host. The underlying mechanisms remain elusive. Here we carried out functional analyses of a flagellar axonemal inner-arm dynein complex in the bloodstream form and investigated its mechanistic role in cytokinesis initiation. We showed that the axonemal inner-arm dynein heavy chain TbIAD5-1 and TbCentrin3 form a complex, localize to the flagellum, and are required for viability in the bloodstream form. We further demonstrated the interdependence between TbIAD5-1 and TbCentrin3 for maintenance of protein stability. Finally, we showed that depletion of TbIAD5-1 and TbCentrin3 arrested cytokinesis initiation and disrupted the localization of multiple cytokinesis initiation regulators. These findings identified the essential role of an axonemal inner-arm dynein complex in cell division, and provided molecular insights into the flagellum motility-mediated cytokinesis initiation in the bloodstream form of T. brucei.


The vertebrate protein CTCF functions as an insulator in Saccharomyces cerevisiae.
Insulators are elements that shelter genes from the effects of silencers or enhancers. CTCF is the only vertebrate protein that has a recognized role in transcriptional insulation, but how it exerts its effect is unknown. In an attempt to better understand how CTCF functions, we have used an insulation assay in Saccharomyces cerevisiae. We show that CTCF acts as an insulator in yeast, where it can efficiently block the spreading of repressive telomeric chromatin. We identify two domains of the protein that are responsible for this activity: a short and very potent N-terminal domain, as well as the C-terminus of the protein.


Role of homocysteine in the development and progression of Parkinson's disease.
Homocysteine is an essential intermediate product of biochemical reactions that is present in various tissues of the human body. Homocysteine may be associated with the development and progression of Parkinson's disease. Plasma homocysteine levels in patients with Parkinson's disease are elevated compared to those of healthy individuals. High homocysteine drives PD development and progression while aggregating the clinical symptoms of PD patients. The relationship between PD and homocysteine involves multiple pathways, including nerve cell apoptosis, oxidative stress, and DNA damage. This is crucial for explaining how high homocysteine drives the PD procession. Elevated homocysteine level during PD development and progression offers a new strategy for the diagnosis and treatment of this disease.


Absence of inhibitory dopaminergic control of the rabbit pituitary gland intermediate lobe.
No immunoreactive axons were detected with an antiserum against tyrosine hydroxylase in the rabbit intermediate lobe (IL), which thus appears to be devoid of dopaminergic (DA) innervation. Dopamine and its agonists, which classically inhibit alpha-MSH release have no inhibitory effects on rabbit IL superfused in vitro but, paradoxically, stimulate alpha-MSH release. D2 type DA receptors, known to mediate inhibitory control of dopamine on melanotropic cells, and detectable by their affinity for (3H)-spiroperidol, were as previously reported absent from the rabbit IL. The absence of (3H)-spiroperidol binding sites in the IL was further confirmed on rabbit pituitary sections by radioautography. The mechanism of DA stimulation is still not clear, but might be tentatively explained by interference with other receptors involved in the stimulation of the gland. The lack of DA inhibitory control over the rabbit IL is an exception among the species so far studied.


Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.
Lymphoma (lymphosarcoma) is the second most frequent cancer in dogs and is clinically comparable to human non-Hodgkin lymphoma. Factors affecting canine lymphoma progression are unknown and complex, but there is evidence that genetic mutations play an important role. We employed Next Gen DNA sequencing of six dogs with multicentric B-cell lymphoma undergoing CHOP chemotherapy to identify genetic variations potentially impacting response. Paired samples from non-neoplastic tissue (blood mononuclear cells) and lymphoma were collected at the time of diagnosis. Cases with progression free survival above the median of 231 days were grouped as 'good' responders and cases below the median were categorized as 'poor' responders. The average number of variants found was 17,138 per case. The variants were filtered to examine those with predicted moderate or high impacts. Many of the genes with variants had human orthologs with links to cancer, but the majority of variants were not previously reported in canine or human lymphoma. Seven genes had variants found in the cancers of at least two 'poor' responders but in no 'good' responders: ATRNL1, BAIAP2L2, ZNF384, ST6GALNAC5, ENSCAFG00000030179 (human ortholog: riboflavin kinase RFK), ENSCAFG00000029320, and ENSCAFG00000007370 (human ortholog: immunoglobin IGKV4-1). Two genes had variants found in the cancers of at least two 'good' responders but in no 'poor' responders: COX18 and ENSCAFG00000030512. ENSCAFG00000030512 has no reported orthologue in any other species. The role of these mutations in the progression of canine lymphoma requires further functional analyses and larger scale study.


Target Gene Diversity of the Nrf1-MafG Transcription Factor Revealed by a Tethered Heterodimer.
Members of the cap'n'collar (CNC) family of transcription factors, including Nrf1 and Nrf2, heterodimerize with small Maf (sMaf) proteins (MafF, MafG, and MafK) and regulate target gene expression through CNC-sMaf-binding elements (CsMBEs). We recently developed a unique tethered dimer assessment system combined with small Maf triple-knockout fibroblasts, which enabled the characterization of specific CNC-sMaf heterodimer functions. In this study, we evaluated the molecular function of the tethered Nrf1-MafG (T-N1G) heterodimer. We found that T-N1G activates the expression of proteasome subunit genes, well-known Nrf1 target genes, and binds specifically to CsMBEs in the proximity of these genes. T-N1G was also found to activate genes involved in proteostasis-related pathways, including endoplasmic reticulum-associated degradation, chaperone, and ubiquitin-mediated degradation pathways, indicating that the Nrf1-MafG heterodimer regulates a wide range of proteostatic stress response genes. By taking advantage of this assessment system, we found that Nrf1 has the potential to activate canonical Nrf2 target cytoprotective genes when strongly induced. Our results also revealed that transposable SINE B2 repeats harbor CsMBEs with high frequency and contribute to the target gene diversity of CNC-sMaf transcription factors.


Investigating the impact of eight weeks of aerobic and resistance training on blood lipid profile in elderly with non-alcoholic fatty liver disease: a randomized clinical trial.
The aim of this study was to investigate the effects of eight weeks aerobic and resistance exercise on blood lipid profile in elderly with non-alcoholic fatty liver disease (NAFLD). Increased sedentary have a potential role in the development of NAFLD. Exercise training as an effective strategy to reduce NAFLD is presented. In a randomized clinical trial study, thirty nine elderly patients with NAFLD were enrolled and were randomly divided in three groups. Aerobic groups (AG, n=13), resistance group (RG, n=13) and control group (CG, n=13). AG participated in an 8-week aerobic training (three 45-min sessions per week at 55-75% of HRR (heart rate reserve)). RG participated in an 8-week resistance exercises (three 45-min sessions per week at 50-70% of 1RM (one-repetition measure). Blood lipid profile of patients were evaluated baseline and after eight weeks. At baseline, there were no differences between the two groups. In two group, cholesterol and low density lipoprotein (LDL) of blood of elderly follow eight weeks aerobic training with p=0.02 and p=0.02 were decreased, respectively. Also, High density lipoprotein (HDL) was improved follow aerobic training (p=0.008). However, the aerobic and resistance training were not effective on triglyceride (TG). aerobic training was more effective than resistance training in improving the blood lipid profile in elderly with NAFLD and can role in management of this condition.


Unusual cause of hoarseness: Arytenoid cartilage dislocation without a traumatic event.
Arytenoid cartilage dislocation is a rare but curable cause of hoarseness and is commonly related to intubation or laryngeal trauma. We present a case of arytenoid cartilage dislocation without a traumatic event in a man who complained of acute hoarseness. An 82-year-old man visited our emergency department complaining of acute hoarseness. He had no history of general anesthesia or laryngeal trauma and had not caught a cold. He showed no abnormal physical findings including the pharynx. Examination using a laryngoscope revealed that the left vocal fold was fixed in the paramedian position. We performed contrast-enhanced computed tomography (CT), but we could not find any cause of the left recurrent laryngeal nerve paralysis. His hoarseness persisted for one month and the initial CT was therefore reassessed. It was found that the left arytenoid cartilage was dislocated forward, and we therefore made a diagnosis of arytenoid cartilage dislocation without a traumatic event. We tried to refer him to an otolaryngologist for surgical treatment, but he declined. Fortunately, his hoarseness gradually improved over a period of two months. Arytenoid cartilage dislocation rarely occurs without a traumatic event. CT is useful for accurate diagnosis of this condition. Since early diagnosis can lead to appropriate surgical treatment and improvement in vocal function, the possibility of arytenoid cartilage dislocation should be considered in patients with acute hoarseness without apparent causes.


Hemostatic efficacy of local chitosan linear polymer granule in an experimental sheep model with severe bleeding of arteria and vena femoralis.
The aim of the present study was to evaluate the hemostatic effect of chitosan linear polymer in a sheep model with femoral bleeding. Following induction of anesthesia and intubation of sheep, groin injury was induced to initiate hemorrhage. Animals were randomly assigned to study and control groups. In the control group, absorbent pads were packed on the wound, and pressure was supplied by a weight placed over the dressing. In the study group, chitosan linear polymer was poured onto the bleeding site; absorbent pads and pressure were applied in the same manner. At 5-min intervals, bleeding was evaluated. Primary endpoint was time to hemostasis. Bleeding had stopped by the 1st interval in 5 members of the study group, and by the 2nd interval in 1 member. One sheep was excluded. The bleeding stopped after the 1st interval in 1 member of the control group and after the 2nd interval in 4 members. Bleeding stopped in 2 cases following ligation of the bleeding vessel. Hemostasis was achieved earlier in the study group, compared to the control group, and the difference was statistically significant. Hemostasis was achieved earlier following application of chitosan linear polymer.


Extra-Virgin Olive Oils from Nine Italian Regions: An ¹H NMR-Chemometric Characterization.
Extra-virgin olive oil (383 samples; EVOOs) of three consecutive harvesting years from nine Italian regions were collected and submitted to an ¹H NMR-chemometric protocol to characterize the samples according to their origin (geographical area and variety). A more complete assignment of the olive oil ¹H spectrum in CDCl₃ and DMSOd₆ was reported identifying 24-methylencycolartanol. A single classification model provided the discrimination of EVOOs among the three geographical macro-areas (North, Islands, Center-South), whereas a hierarchical approach based on breaking the overall classification problem into a series of smaller linear discriminant analysis (LDA) sub-models was tested to differentiate olive oils according to their geographical regions. Specific compounds responsible for olive oil characterization were identified.


Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model.
Pancreatic cancer (PC) represents an intriguing topic for researchers. To date, the prognosis of metastasized PC is poor with just 7% of patients exceeding a five-year survival period. Thus, molecular modifications of existing drugs should be developed to change the course of the disease. Our previously generated nanocages of Mitoxantrone (MIT) encapsulated in human H-chain Ferritin (HFt), designated as HFt-MP-PASE-MIT, has shown excellent tumor distribution and extended serum half-life meriting further investigation for PC treatment. Thus, in this study, we used the same nano-formulation to test its cytotoxicity using both in vitro and in vivo assays. Interestingly, both encapsulated and free-MIT drugs demonstrated similar killing capabilities on PaCa44 cell line. Conversely, in vivo assessment in a subcutaneous PaCa44 tumor model of PC demonstrated a remarkable capability for encapsulated MIT to control tumor growth and improve mouse survival with a median survival rate of 65 vs. 33 days for loaded and free-MIT, respectively. Interestingly, throughout the course of mice treatment, MIT encapsulation did not present any adverse side effects as confirmed by histological analysis of various murine tissue organs and body mass weights. Our results are promising and pave the way to effective PC targeted chemotherapy using our HFt nanodelivery platforms.


The challenging management of cardiac involvement in systemic sarcoidosis.
A 34 year-old young man came to our attention after an occasional finding of complete AV block. We made the diagnosis of systemic sarcoidosis with cardiac involvement through an FDG-PET even with a normal CMR. We started corticosteroid therapy and we decided to follow-up the patient through an implantable loop recorder (ILR). Beyond an initial regression of the AV block, after 8 months the ILR revealed AV block and pauses more than 3 s during the day; a new FDG-PET evidenced FDG uptake in new areas of left ventricle. Hence we started infliximab and implanted a dual chamber ICD.


Cocaine detection in neonatal gastric aspirate samples.
We prospectively analyzed the feasibility and sensitivity of gastric fluid detection of cocaine compared with standard meconium analysis. Cocaine was detected in nearly half (45.5%) of gastric aspirate samples tested from infants in whom meconium was positive for cocaine. The time to sample acquisition was substantially shorter for gastric aspirate sampling versus meconium analysis. The possible ramifications of the presence of cocaine in amniotic fluid are discussed.


Evaluating clinical impact of a shortened infusion duration for ramucirumab: a model-based approach.
We investigated the impact of infusion duration (30 and 60 min) on the pharmacokinetic profile of ramucirumab using a population pharmacokinetic (PopPK) modeling approach. We also assessed the relationship between infusion rate and incidence of immediate infusion-related reactions (IRRs; occurring on the day of administration) using ramucirumab phase II/III study data. The impact of different infusion durations (30 vs. 60 min) on the time-course of ramucirumab concentration profiles were evaluated using a PopPK model, established using ramucirumab pharmacokinetic data from 2522 patients. Logistic regression was used to evaluate the association between ramucirumab infusion rate and incidence of immediate IRRs in clinical trials. Ramucirumab time-course concentration profiles were equivalent following a 30- or 60-min infusion. In the pooled clinical study dataset, 254 of 3216 (7.9%) patients receiving ramucirumab experienced at least one immediate IRR (any grade). When grouped according to infusion rate quartile, the incidence of immediate IRRs (any grade or grade ≥ 3) was similar across quartiles; findings were confirmed in sensitivity analyses. The risk of immediate IRRs was not found to be associated with infusion rate based on multivariate logistic analysis. Shortening the infusion duration of ramucirumab from 60 to 30 min has no impact on ramucirumab exposure. Analysis of trial data found no relationship between an increased risk of immediate IRRs and a faster infusion rate. Such a change in infusion duration is unlikely to affect the clinical efficacy or overall safety profile of ramucirumab.


Description of Paracymbiomma gen. nov., a new genus of prodidomid spiders from the Neotropical region (Araneae: Prodidomidae) including a new troglobite species.
Paracymbiomma gen. nov. is proposed to include six new species from Brazil: P. angelim sp. nov. (♂ ♀) from São Paulo, P. carajas sp. nov. (♂ ♀), P. bocaina sp. nov. (♂ ♀) and P. caecus sp. nov. (♂ ♀) from Pará, P. doisirmaos sp. nov. (♂) from Pernambuco and P. pauferrense sp. nov. (♂) from Paraíba. The genus is included in Theuminae by having the sternum with posterior region without rebordered margins, strongly protruding between coxae IV and with numerous long and erect setae, and by the vulva with highly convoluted ducts. It can be distinguished from the other members of the subfamily by the male palp with paracymbium, single RTA, bulb with sclerotized conductor and partly sclerotized median apophysis, and by the female epigyne with posteromedian atrium and sclerotized margin, and vulva with copulatory ducts long, strongly convoluted laterally with proximal part (closest to copulatory openings) translucent. Paracymbiomma carajas sp. nov., P. bocaina sp. nov. and P. caecus sp. nov. occur exclusively in ferruginous caves. We provide a discussion on specializations and adaptations of Paracymbiomma gen. nov. and other species of Prodidomidae to the subterranean environment.


Intake of added oils and fats among middle-aged French adults: relationships with educational level and region of residence.
To describe the relative contribution of 10 created food groups to total fat intake in middle-aged subjects. The relationship of added oil and fat intake with region of residence and educational level was also assessed. Cross-sectional study. Participants of the French Supplémentation en Vitamines et Minéraux Antioxydants study who completed at least six 24-hour dietary records after inclusion into the study (N=6,572). Added oils and fats were the main source of total fat intake. Animal fat and margarine intakes showed a significant inverse association with educational level, whereas oils with monounsaturated fatty acids (MUFA) were positively associated with education level. Animal fat intake was significantly higher in the western and northern parts of France (54.2% and 50.4%) and lower in the Mediterranean Coast (39.0%). A significant inverse gradient was found with oils with polyunsaturated fatty acids or MUFA in the southwest and the Mediterranean Coast compared with the northern part of France. We showed a north to south gradient for animal fat intake and the opposite for oils with MUFA and polyunsaturated fatty acid in France. This gradient parallels the known disparities for cardiovascular mortality in this country. This should contribute to adapting dietary guidelines for dietary change in a public health perspective.


Psychological profile of patients suffering from Crohn's disease and ulcerative colitis.
Patients with Crohn's disease (CD, n = 61) and ulcerative colitis (UC, n = 24) were studied using an interview and a series of percept-genetic tests describing anxiety, defensive strategies, and the self-image. Attention was specifically directed at a subgroup of CD (n = 15) with its inflammation limited to the colon (colon Crohn, CC). There was also a control group (n = 43). CC had more immature parent relations than the other groups. They were more childishly concrete and more alexithymic. While CC differ from other Crohn patients in many respects, the real cleft opens up with regard to UC, in spite of location of their illness. CC patients obviously have a psychological profile of their own.


Duodenal juice stimulates oesophageal stem cells to induce Barrett's oesophagus and oesophageal adenocarcinoma in rats.
the present study was performed to examine the sequential process of the development of Barrett's oesophagus (BE) and oesophageal adenocarcinoma (ADC) induced by duodeno-oesophageal reflux (DER) in rats. Total gastrectomy was performed in male Wistar rats weighing approximately 250 g followed by reconstruction with oesophago-jejunostomy, which causes unavoidable DER without exposure to exogenous carcinogens. Animals were selected at random and sacrificed every 10 weeks after surgery until 50 weeks. Severe squamous oesophagitis with erosion, regenerative thickening (RT), and basal cell hyperplasia (BCH) were observed on the 10th week after surgery. On the 20th week, glandular structures that stained positively with Galactose oxidase-Schiff (foveolar metaplasia) were observed in the basal layer of the oesophageal squamous epithelium. On the 30th week, the glands developed and formed cysts that stained positively with concanavalin A (pyloric glandular metaplasia) and/or high-iron diamine and Alcian blue (intestinal metaplasia). From the 40th week after surgery, ADC cells surrounded by columnar-lined epithelium were found. Persistent stimulation with DER can alter the stem cells in the squamous epithelial basal layer leading to the formation of columnar-lined cells and subsequent ADC. Foveolar metaplasia was observed as part of the sequence of events leading to the development of columnar-lined epithelium (CLE), followed by the appearance of pyloric glandular metaplasia and intestinal metaplasia, completing the histogenesis of BE.


Quadrupolar particles in a nematic liquid crystal: effects of particle size and shape.
We investigate the effects of particle size and shape on the quadrupolar (Saturn-ring-like) defect structures formed by a nematic liquid crystal around nm-sized and mum -sized particles with spherical and spherocylindrical shapes. We also report results for the potentials of mean force in our systems, calculated using a mesoscale theory for the tensor order parameter Q of the nematic. Our results indicate that for pairs of nm-sized particles in close proximity, the nematic forms "entangled hyperbolic" defect structures regardless of the shape of the nanoparticles. In our calculations with nanoparticles we did not observe any other entangled or unentangled defect structures, in contrast to what was reported for pairs of mum -sized spherical particles. Such a finding suggests that the "entangled hyperbolic" defect structures are the most stable for pairs of nanoparticles in close proximity. For pairs of mum -sized particles, our results indicate that the nematic forms entangled "figure-of-eight" defect structures around pairs of spheres and spherocylinders. Our results suggest that the transition between "entangled hyperbolic" and figure-of-eight defect structures takes place when the diameter of the particle is between D=100 nm and 1 microm . We have also calculated the torques that develop when pairs of spherocylindrical nanoparticles in a nematic approach each other. Our calculations suggest that the nematic-mediated interactions between the nm-sized particles are fairly strong, up to 5700 k{B}T for the case of pairs of spherocylindrical nanoparticles arranged with their long axis parallel to each other. Furthermore, these interactions can make the particles to bind together at specific locations, and thus could be used to assemble the particles into ordered structures with different morphologies.


Bioinspired Anti-Oil-Fouling Hierarchical Structured Membranes Decorated with Urchin-Like α-FeOOH Particles for Efficient Oil/Water Mixture and Crude Oil-in-Water Emulsion Separation.
Designing and constructing a stable water-retention layer acting as the isolation between the oil and membrane surface holds great significance for solving the membrane fouling problems in oil/water separation, including common layered oil/water mixtures, immiscible oil-in-water emulsions, and even high-viscosity crude oil-in-water emulsions. Inspired by the self-cleaning property of sea urchin thorns, a bioinspired anti-oil-fouling hierarchically structured membranes decorated with urchin-like α-FeOOH particles was successfully prepared via the layer-by-layer (LBL) self-assembly method, maintaining numerous effective micro-nanopores. The hierarchical structured membrane exhibited superior superhydrophilicity/underwater superoleophobicity, high water-retention ability, and preferable anti-oil-fouling properties. Furthermore, the biomimetic membrane with controllable pore sizes could not only separate common layered oil/water mixtures but also effectively separate immiscible surfactant-stabilized oil-in-water emulsions of both low-viscosity crude oil and high-viscosity crude oil with an ultrahigh water flux up to 2598.4 L m-2 h-1 and an outstanding separation efficiency of 98.5%, revealing its promising prospect in oily wastewater treatment.


Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents.
Serum levels of total insulin-like growth factor I (IGF-I) correlate with growth hormone (GH) secretory status and are a useful parameter in the diagnostic evaluation of GH deficiency. Serum total IGF-I levels represent the combined quantity of free or unbound IGF-I and IGF-I that is bound to specific IGF binding proteins. Free IGF-I (fIGF-I), which is postulated to be the bioactive fraction, accounts for only a small fraction of the total amount. We have recently developed a new immunoradiometric assay (IRMA) for plasma fIGF-I and have investigated fIGF-I in relation to GH status. The simple, non-extraction assay procedure involves the capture of unbound IGF-I by anti-IGF-I antibody coated to polystyrene beads and detection by a radiolabelled anti-IGF-I antibody directed to a separate epitope. Preliminary studies demonstrated that the fIGF-I IRMA does not measure IGF-I that is complexed to IGF-binding proteins and that the equilibrium between the free and bound fractions is not disturbed during the assay. Free IGF-I levels were compared to total IGF-I levels measured in the same IRMA after acid-ethanol extraction of the samples. Normal levels of fIGF-I from infancy through adulthood were found to have a close correlation with total IGF-I levels, with the lowest levels occurring in infancy and peak levels during puberty. Patients with complete GH deficiency had low levels of both fIGF-I and total IGF-I, with 94% and 100% of the levels below the 5ht percentile for age, respectively. On the other hand, approximately 90% of patients with normal IGF binding protein-3 levels among partial GH deficiency and normal short children had free and total IGF-I levels above the 5th percentile for age. These data indicate that the clinical utility of plasma fIGF-I measurements is similar to measurements of total IGF-I in the evaluation of childhood GH deficiency.


Oxygen transport and organ dysfunction in the older trauma patient.
To determine baseline values of cardiac index (CI) and oxygen transport variables in patients with multiple trauma within 24 hours of admission to a level I trauma center. This project was part of a larger study comparing methods of measuring oxygen consumption (VO2) in 38 severely injured patients. Measurements of CI, oxygen delivery (DO2), and VO2 were performed every 6 hours for 24 hours. Patients were monitored for multiple organ dysfunction syndrome. The mean age was 59 (+/- 17) years, with 74% (n = 28) of patients 50 years or older. Patients 65 years or older had significantly lower levels of CI, DO2, and VO2. Initial age-related differences in CI (P < .001) persisted at each time period (P < .0136). Younger patients generated a higher DO2 at each time period (P < .0005). Even though there were persistent age-related differences in VO2 over time (P < .0001), no interaction between age and time was found. Survivors had lower scores for multiple organ dysfunction syndrome than did nonsurvivors (P < .0001), all of whom were 50 years or older. Mortality was 21%. All patients were hypermetabolic, but older patients were much less so. Younger patients progressively had increased CI and DO2 levels, whereas older patients started with low levels that remained so. Patients in each age group appeared to lock into a level of VO2 that did not change over time. These findings underscore the vulnerability of older patients to poor outcomes. As the magnitude of the postinjury response is partly age-dependent, future research should differentiate patient characteristics associated with positive outcomes among elderly trauma patients.


Photochemical Synthesis of 1,4-Dicarbonyl Bifluorene Compounds via Oxidative Radical Coupling Using TEMPO as the Oxygen Atom Donor.
A visible-light-induced metal-free synthesis of 1,4-dicarbonyl compounds from alkyne-containing aryl iodides via photochemical C-I bond cleavage, intramolecular cyclization, oxidation, and intermolecular radical coupling sequence is reported. TEMPO was employed as the oxygen atom donor in this transformation. This protocol provided a new strategy for the synthesis of 1,4-dicarbonyl bifluorene compounds.


2-(Methoxycarbonyl)phenylboronic acid.
The structure of the title compound, 2(CH3OCO)C6H4B(OH)2 or C8H9BO4, involves two crystallographically independent conformers, A and B, in a 1:2 ratio; molecules of conformer A are located on a crystallographic mirror plane. The most striking difference between the two independent molecules is the opposite orientation of the methoxycarbonyl groups, while the conformations of the boronic acid groups vary more subtly. Molecules of both types are ordered to produce a specific hydrogen-bonding network that can be interpreted in terms of a layer lying parallel to (100). Within the layer, B molecules are linked with each other by two different O-H...O bonds to form an infinite chain where two centrosymmetric dimeric motifs can be distinguished.


The total cost of hip-joint replacement; a model for purchasers.
A computer-based model is used to investigate the total cost of primary total hip-joint replacement. The model takes into account the probability of prosthesis failure, death and re-revision. The results emphasize the importance of age at insertion, demonstrating that the expected life-span of the patient has a major influence on the total cost for a given prosthesis. The discussion considers the idea of a 'lifetime care package' to encapsulate the concept of quality when considering the purchasing of total hip replacements. If it is assumed that a primary replacement episode costs 3500 pounds and revision surgery costs twice as much, then the additional premium on the best implant currently available would be 630 pounds. The premium payable on the same patient using the worst design would be 3080 pounds. This difference reflects the importance of quality in total hip replacement surgery.


Improved sparse domain super-resolution reconstruction algorithm based on CMUT.
A novel breast ultrasound tomography system based on a circular array of capacitive micromechanical ultrasound transducers (CMUT) has broad application prospects. However, the images produced by this system are not suitable as input for the training phase of the super-resolution (SR) reconstruction algorithm. To solve the problem, this paper proposes an improved medical image super-resolution (MeSR) method based on the sparse domain. First, we use the simultaneous algebraic reconstruction technique (SART) with high imaging accuracy to reconstruct the image into a training image in a sparse domain model. Secondly, we denoise and enhance the contrast of the SART images to obtain improved detail images before training the dictionary. Then, we use the original detail image as the guide image to further process the improved detail image. Therefore, a high-precision dictionary was obtained during the testing phase and applied to filtered back projection SR reconstruction. We compared the proposed algorithm with previously reported algorithms in the Shepp Logan model and the model based on the CMUT background. The results showed significant improvements in peak signal-to-noise ratio, entropy, and average gradient compared to previously reported algorithms. The experimental results demonstrated that the proposed MeSR method can use noisy reconstructed images as input for the training phase of the SR algorithm and produce excellent visual effects.


Concurrent and Longitudinal Predictors of Adolescent Delinquency in Mainland Chinese Adolescents: The Role of Materialism and Egocentrism.
Although studies have examined the influence of materialism on adolescent well-being, there are several methodological limitations: studies examining the influence of materialism on adolescent delinquency are almost non-existent; researchers commonly used cross-sectional designs; the sample size in some studies was not large; validated measures on materialism in non-Western contexts are rare; there are very few Chinese studies. Besides, no study has examined the hypothesis that egocentrism is the mediator in the influence of materialism on adolescent delinquency. Using a short-term longitudinal design, two waves of data were collected from 2648 early adolescents in mainland China. At each wave, students completed validated measures of materialism, egocentrism and delinquent behavior. Materialism and egocentrism positively predicted adolescent delinquency at Wave 1 and Wave 2 and over time. While materialism at Wave 1 positively predicted increase in delinquency over time, egocentrism did not. However, PROCESS analysis showed that egocentrism mediated the longitudinal influence of materialism on adolescent delinquent behavior. Materialism and egocentrism are predictors of adolescent delinquency, with egocentrism serving as a mediator in the influence of materialism on adolescent delinquency.


A sustainable artificial intelligence facilities management outsourcing relationships system: Case studies.
The purpose of this article was to validate the published artificial intelligence (AI) facilities management (FM) outsourcing relationships system by real business cases in the working environment. The research aims to inspire the modern FM professionals in different industries with some challenging and innovative concepts about FM outsourcing relationships between facilities owners and service providers. First, it will briefly introduce the theory of the FM outsourcing relationships system on how it can help the FM seniors and strategists to design their FM daily strategies wisely and make their business more effective and productive. Second, it will also introduce what the research is practically doing in the stage of case study for test and verification. It is concluded that FM outsourcing categorization may help to define the appropriate relationships. This further detailed outcome generated from the AI can be considered a solid reference to define and explain the existing outsourcing relationships between the stakeholders and the service providers to assign an outsourcing category to the FM relationship between the client and service provider based on the learnt rules.


Assessing the risks of West Nile virus-infected mosquitoes from transatlantic aircraft: implications for disease emergence in the United Kingdom.
The number of West Nile virus (WNV)-infected mosquitoes aboard aircraft from the United States that arrive in the United Kingdom each summer was determined using a quantitative risk assessment. In the worst-case scenario, when WNV levels in mosquitoes are high (at epidemic levels) the probability of at least one WNV-infected mosquito being introduced into the United Kingdom was predicted to be 0.99. During these periods, a mean of 5.2 infected mosquitoes were estimated to be aboard flights from the United States to the United Kingdom during May to October, with 90% certainty that the exact value lies between one and ten mosquitoes. Heathrow airport was predicted to receive the majority of the infected mosquitoes (72.1%). Spatial analysis revealed the region surrounding Heathrow satisfies the criteria for potential WNV exposure as both WNV-competent mosquitoes and susceptible wild bird species are present. This region is, therefore, recommended for targeted, risk-based surveillance of WNV-infected mosquitoes in addition to an increased awareness of the risks to horses, birds and humans.


Novel targets for detection of cancer and their modulation by chemopreventive natural compounds.
Cancer affects the lives of millions of people. Several signaling pathways have been proposed as therapeutic targets for cancer therapy, and many more continue to be validated. With the identification and validation of therapeutic targets comes the question of designing novel strategies to effectively counter such targets. Natural compounds from dietary sources form the basis of many ancient medicinal systems. They are pleiotropic i.e. they act on multiple targets, and, therefore, are often the first agents to be tested against a novel therapeutic target. This review article summarizes the knowledge so far on some actively pursued targets - Notch, CXCR4, Wnt and sonic hedgehog (shh) pathways, the process of epithelial-mesenchymal transition (EMT) as well as molecular markers such as uPA-uPAR, survivin, FoxM1, and the microRNAs. We have performed an extensive survey of literature to list modulation of these targets by natural agents such as curcumin, indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM), resveratrol, epigallocatechin-3-gallate (EGCG), genistein etc. We believe that this review will stimulate further research for elucidating and appreciating the value of these wonderful gifts from nature.


Localization of the pH gate in Kir1.1 channels.
We used cysteine-modifying reagents to localize the pH-sensitive gate in the renal inward-rectifier K(+) channel Kir1.1a (ROMK1). Cytoplasmic-side methanethiosulfonate (MTS) reagents blocked K(+) permeation in native Kir1.1 channels, expressed in Xenopus oocytes. Replacement of three cysteines in the N-terminus, C-terminus, and transmembrane domains eliminated this sensitivity to MTS reagents, as measured with inside-out macropatches. Reintroduction of one cysteine at 175-Kir1.1a in the second transmembrane domain allowed blockade of the open channel by the MTS reagents MTSEA, MTSET, and MTSES and by Ag(+). However, closure of the channel by low pH protected it from modification. Cysteine was also introduced into position G223, which is thought to line the cytoplasmic pore of the channel. MTSET blocked G223C in both the open and closed state. In contrast, MTSEA reduced G223C single-channel conductance from 40 to 23 pS but did not produce complete block. We conclude that cytoplasmic acidification induces a conformational change in the channel protein that prevents access of cysteine-modifying reagents, and presumably also K(+) ions, to the transmembrane pore from the cytoplasm. This is consistent with localization of the Kir1.1 pH gate at the helix bundle crossing near the cytoplasmic end of the transmembrane pore.


Economic evaluation of a randomized controlled trial comparing mifepristone and misoprostol with misoprostol alone in the treatment of early pregnancy loss.
In case of early pregnancy loss (EPL) women can either choose for expectant, medical or surgical management. One week of expectant management is known to lead to spontaneous abortion in approximately 50% of women. Medical treatment with misoprostol is known to be safe and less costly than surgical management, however less effective in reaching complete evacuation of the uterus. Recently, a number of trials showed that prompt treatment with the sequential combination of mifepristone with misoprostol is superior to misoprostol alone in reaching complete evacuation. In this analysis we evaluate whether the sequential combination of mifepristone with misoprostol is cost-effective compared to misoprostol alone, in the treatment of EPL. A cost-effectiveness analysis (CEA) from a healthcare perspective was performed alongside a randomised controlled trial (RCT) in which standard treatment with misoprostol only was compared with a combination of mifepristone and misoprostol, in women with EPL after a minimum of one week of unsuccessful management. A limited societal perspective scenario was added. This RCT, the Triple M trial, was a multicentre, randomized, double-blinded, placebo-controlled trial executed at 17 hospitals in the Netherlands. The trial started on June 27th 2018, and ended prematurely in January 2020 due to highly significant outcomes from the predefined interim-analysis. We included 351 women with a diagnosis of EPL between 6 and 14 weeks gestation after at least one week of unsuccessful expectant management. They were randomized between double blinded pre-treatment with oral mifepristone 600mg (N = 175) or placebo (N = 176) taken on day one, both followed by misoprostol orally. In both groups, an intention-to-treat analysis was performed for 172 patients, showing a significant difference in success rates between participants treated with mifepristone and misoprostol versus those treated with misoprostol alone (79.1% vs 58.7% respectively). In this cost-effective analysis we measured the direct, medical costs related to treatment (planned and unplanned hospital visits, medication, additional treatment) and indirect costs based on the IMTA Productivity Cost Questionnaire (iPCQ). Quality Adjusted Life Years (QALY's) were calculated from participants' scores on the SF-36 questionnaires sent digitally at treatment start, and one, two and six weeks later. We found medical treatment with placebo followed by misoprostol to be 26% more expensive compared to mifepristone followed by misoprostol (p = 0.001). Mean average medical costs per patient were significantly lower in the mifepristone group compared to the placebo group (€528.95 ± 328.93 vs €663.77 ± 456.03, respectively; absolute difference €134.82, 95% CI 50,46-219,18, p = 0.002). Both indirect costs and QALY's were similar between both groups. The sequential combination of mifepristone with misoprostol is cost-effective compared with misoprostol alone, for treatment of EPL after a minimum of one week of unsuccessful expectant management.


[Acute surgical treatment of malignant stroke].
Malignant stroke is an intracranial herniation syndrome caused by cerebral oedema after a large hemispheric or cerebellar stroke. Malignant middle cerebral artery infarction is a devastating disease with a mortality around 80% despite intensive medical treatment. Decompressive craniectomy reduces mortality and improves functional outcome - especially in younger patients (age ≤ 60 years). Decompression of the posterior fossa is a life-saving procedure in patients with malignant cerebellar infarctions and often leads to good neurological outcome.


Burs with guide pins for standardized tooth preparation.
The aim of this study was to develop and test self-limiting diamond burs to ease precise chamfer preparation and to fulfill the special requirements of computer-aided design/computer-aided manufacturing and all-ceramic restorations. Rounded cylinder (based on ISO 881) and torpedo (based on ISO 879) diamond burs with a polished guide pin, 0.5 mm in length and 0.15 mm in radius, at the front end were developed in cooperation with an industrial partner. The in vitro testing involved a total of 140 human teeth. Experimental variables were the quality of the finish line, the microhardness of the enamel, and the thermal alteration of the dentin. Conventional diamonds served as a control. No mechanical or thermal damage related to the bur design was found in the hard tissues that had potentially been in contact with or in close proximity to the guide pin. Microhardness of the enamel at the finish line was significantly higher when prepared with burs with a guide pin compared to conventional burs. The results of using the guide pin might indicate the beneficial effect of reduced vibration. The guide pins of the self-limiting diamond burs reduce, rather than increase, the risk of hard tissue damage at the preparation margin. No adverse effects were found. Clinical use is justified.


[Cure of cystocele with vaginal patch].
To describe an original technique for transvaginal cystocele repair and to report the anatomical and functional results of the first 47 patients operated by this technique. The operation combines suspension, by six sutures to the tendinous arches of the pelvic fascia, of a vaginal patch measuring 6 to 8 cm long by about 4 cm wide left in contact with the cystocele. The vaginal patch is then buried under the anterior colporraphy suture. Spinal fixation, hysterectomy, levator myorrhaphy or urinary incontinence repair are also performed as necessary. Descriptive retrospective study of 47 patients undergoing transvaginal repair of prolapse between October 1997 and June 1998. All patients presented external prolapse with grade III cystocele, associated with urinary incontinence in 38.3% of cases and hysterocele or vaginal prolapse in 87% of cases. The mean age of the patients was 69 years. The uterus was preserved in two cases, but hysterectomy was performed in the other 45 patients, together with Richter spinal fixation in 44 cases An associated levator myorrhaphy was performed in every case. The mean follow-up was 16.4 months (range: 6 to 26 months) in 46 patients. The cystocele was considered to be cured in 93% of patients, one patient had an asymptomatic grade I cystocele and surgery was unsuccessful in two patients who developed recurrent grade II cystocele. The technique presented here is a curative treatment for grade III cystocele in menopaused women associated with Richter spinal fixation, and prevents the risk of cystocele described after transvaginal treatment of prolapse by spinal fixation alone (10 to 20%). The short-term results are encouraging, but they need to be confirmed by a follow-up of at least 5 years.


Weight gain in pregnancy: can metformin steady the scales?
Metformin has been associated with modest weight reduction in the non-pregnant population. Our hypothesis is that metformin exposure will lead to a higher incidence of appropriate weight gain during pregnancy. This was a retrospective cohort study in a single center between 2009 and 2019. We included all pregnant women with type 2 diabetes or prediabetes. We compared women exposed to metformin in any trimester. The primary outcome was appropriate weight gain defined by the Institute of Medicine guidelines. Secondary outcomes included excessive weight gain, weight loss, suspected fetal growth restriction (FGR), and mean birth weight. Adjusted odds ratios or group differences were calculated using logistic or linear regression, controlling for confounders. Of 41,472 deliveries during the study period, 511 pregnancies met inclusion criteria. 284 pregnancies had no metformin exposure; 227 did have metformin exposure, of which 169 (72.2%) were initiated on metformin in the first trimester. Women exposed to metformin in any trimester were statistically not more likely to have appropriate weight gain (aOR 1.53 (95% CI 1.00-2.34, p = .048), but did have less excess weight gain (aOR 0.45, 95% CI 0.30-0.66, p < .001), and more maternal weight loss (aOR 2.17, 95% CI 1.18-3.98, p = .012) than the unexposed group. Women exposed to metformin in the first trimester of pregnancy were less likely to have excess weight gain (aOR 0.39, 95% CI 0.25-0.61, p < .001) and more likely to have maternal weight loss (aOR 2.56, 95% CI 1.30-5.07, p = .007) than the unexposed cohort. There was no difference in FGR (5.3% vs 2.5% p = .094) or mean birth weight (3235.6 vs 3352.4 gm p = .122) in the metformin exposed group vs non-exposed groups, respectively. Metformin exposure in pregnancy was associated with less excess weight gain and a higher rate of weight loss. There was no difference in FGR or mean birth weight in metformin exposed neonates. This suggests that metformin may help avoid excess weight gain and its associated comorbidities.


On-demand and location selective particle assembly via electrophoretic deposition for fabricating structures with particle-to-particle precision.
Programmable positioning of 2 μm polystyrene (PS) beads with single particle precision and location selective, "on-demand", particle deposition was demonstrated by utilizing patterned electrodes and electrophoretic deposition (EPD). An electrode with differently sized hole patterns, from 0.5 to 5 μm, was used to illustrate the discriminatory particle deposition events based on the voltage and particle-to-hole size ratio. With decreasing patterned hole size, a larger electric field was required for a particle deposition event to occur in that hole. For the 5 μm hole, particle deposition began to occur at 10 V/cm where as an electric field of 15 V/cm was required for particles to begin depositing in the 2 μm holes. The likelihood of particle depositions continued to increase for smaller sized holes as the electric field increased. Eventually, a monolayer of particles began to form at approximately 20 V/cm. In essence, a voltage threshold was found for each hole pattern of different sizes, allowing fine adjustments in pattern hole size and voltage to control when a particle deposition event took place, even with the patterns on the same electrode. This phenomenon opens a route toward controlled, multimaterial deposition and assembly onto substrates without repatterning of the electrode or complicated surface modification of the particles. An analytical approach using the theories for electrophoresis and dielectrophoresis found the former to be the dominating force for depositing a particle into a patterned hole. Ebeam lithography was used to pattern spherical holes in precise configurations onto electrode surfaces, where each hole accompanied a polystyrene (PS) particle placement and attachment during EPD. The versatility of e-beam lithography was utilized to create arbitrary pattern configurations to fabricate particle assemblies of limitless configurations, enabling fabrication of unique materials assemblies and interfaces.


[Exploration on acupuncture regulation pathways based on neurovascular coupling].
On the basis of the consensus that acupuncture can regulate functional activities of nerves and blood vessels, we, in the present paper, discussed the physiological significance of the functional interactions between the two, and put forward a suitability between neurovascular coupling and acupuncture research, and held that the neurovascular coupling may be involved in 3 key links of the peripheral afferent process of acupuncture signals, central integration and regulation of target organs. Based on the differences in the expression of neurovascular coupling in different tissues, we proposed a feasibility of study on the diffe-rence of acupoint efficacies from acupoint-neurovascular coupling-acupuncture effect, and stimulationmethods-neurovascular coupling-acupuncture effect.


Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation.
In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR). The trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53-1.00) and 0.88 (95% CI, 0.57-1.35) (Pinteraction=0.078), for mortality were 0.91 (95% CI, 0.74-1.13) and 0.91 (95% CI, 0.71-1.16) (Pinteraction=0.34), and for major bleeding were 0.50 (95% CI, 0.36-0.70) and 0.75 (95% CI, 0.58-0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR. The benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers' and patients' predicted quality of international normalized ratio control.


Ultrasound Biomicroscopic Evaluation of Uveal Effusion in Acute Primary Angle Closure.
The aim of this study was to determine the prevalence of uveal effusion in acute primary angle closure (APAC), chronic primary angle-closure glaucoma (PACG), and primary open-angle glaucoma (POAG). A total of 152 consecutive patients (287 eyes) with APAC, PACG, and POAG were enrolled in this prospective and observational case series study. Intraocular pressure-lowering medications were used and ultrasound biomicroscopy examination was undertaken to determine the presence of uveal effusion and measure anterior chamber parameters. Overall, uveal effusion was evident in 40 of 194 affected eyes (20.6%) and no uveal effusion was seen in their fellow eyes. The prevalence of uveal effusion in APAC, chronic PACG, and POAG was 29.3%, 10.9%, and 3.1%, respectively (χ=226.63, P<0.001). APAC eyes had the highest prevalence of effusion and no effusion in their fellow eyes. In 40 eyes with uveal effusion, grade 1 effusion was seen in 17 eyes (42.5%), grade 2 in 15 eyes (37.5%), and grade 3 in 8 eyes (20%). In APAC eyes, the difference in the mean anterior chamber depth (ACD) among effusion grades 3, 2, and 1 was significant (F=5.425, P=0.017), and the eyes with grade 3 effusion had shallower ACD compared with grade 1 (P=0.031), but the difference was not significant compared with grade 2 (P=0.368). The eyes with APAC are associated with a higher prevalence of uveal effusion compared with PACG and POAG and probably as a result of rapid reduction in intraocular pressure with aggressive hypotensive therapy and inflammatory response to the process of acute attack.


The Groshong catheter as an intraperitoneal access device in the treatment of ovarian cancer patients.
With the development of new intraperitoneal treatments in ovarian cancer, safe and convenient access to the peritoneal cavity is now required. This report reviews the University of Alabama at Birmingham's experience with the Groshong catheter as an intraperitoneal access device. The Groshong was easily inserted intraperitoneally in 20 ovarian cancer patients and used to deliver 81 courses of intraperitoneal therapy over 2310 patient-days. There were no catheter-related complications during treatment and only one exit site infection after catheter removal. Further investigation of the Groshong catheter as a novel intraperitoneal access device appears warranted.


Creatine feeding increases GLUT4 expression in rat skeletal muscle.
The purpose of this study was to investigate the potential role of creatine in GLUT4 gene expression in rat skeletal muscle. Female Wistar rats were fed normal rat chow (controls) or chow containing 2% creatine monohydrate ad libitum for 3 wk. GLUT4 protein levels of creatine-fed rats were significantly increased in extensor digitorum longus (EDL), triceps, and epitrochlearis muscles compared with muscles from controls (P < 0.05), and triceps GLUT4 mRNA levels were approximately 100% greater in triceps muscles from creatine-fed rats than in muscles from controls (P < 0.05). In epitrochlearis muscles from creatine-fed animals, glycogen content was approximately 40% greater (P < 0.05), and insulin-stimulated glucose transport rates were higher (P < 0.05) than in epitrochlearis muscles from controls. Despite no changes in [ATP], [creatine], [phosphocreatine], or [AMP], creatine feeding increased AMP-activated protein kinase (AMPK) phosphorylation by 50% in rat EDL muscle (P < 0.05). Creatinine content of EDL muscle was almost twofold higher for creatine-fed animals than for controls (P < 0.05). Creatine feeding increased protein levels of myocyte enhancer factor 2 (MEF2) isoforms MEF2A ( approximately 70%, P < 0.05), MEF2C ( approximately 60%, P < 0.05), and MEF2D ( approximately 90%, P < 0.05), which are transcription factors that regulate GLUT4 expression, in creatine-fed rat EDL muscle nuclear extracts. Electrophoretic mobility shift assay showed that DNA binding activity of MEF2 was increased by approximately 40% (P < 0.05) in creatine-fed rat EDL compared with controls. Our data suggest that creatine feeding enhances the nuclear content and DNA binding activity of MEF2 isoforms, which is concomitant with an increase in GLUT4 gene expression.


A case of idiopathic fibrosing pancreatitis.
We experienced a case of chronic fibrosing pancreatitis in an 18/12-year-old girl, which was idiopathic because there were no familial back ground, no cystic fibrosis of pancrease, no ductal anomalies and obstruction. The patient presented intermittent colicky abdominal pain and progressive obstructive jaundice, but T-tube drainage and removal of the lymph nodes around the common bile duct relieved her symptoms and disease process. This seems to be the first case reported in a Korean child. Idiopathic fibrosing pancreatitis should be considered in the differential diagnosis of abdominal pain with obstructive jaundice in children.


A High Throughput and Unbiased Machine Learning Approach for Classification of Graphene Dispersions.
Significant research to define and standardize terminologies for describing stacks of atomic layers in bulk graphene materials has been undertaken. Most methods to measure the stacking characteristics are time consuming and are not suited for obtaining information by directly imaging dispersions. Conventional optical microscopy has difficulty in identifying the size and thickness of a few layers of graphene stacks due to their low photon absorption capacity. Utilizing a contrast based on anisotropic refractive index in 2D materials, it is shown that localized thickness-specific information can be captured in birefringence images of graphene dispersions. Coupling pixel-by-pixel information from brightfield and birefringence images and using unsupervised statistical learning algorithms, three unique data clusters representing flakes (unexfoliated), nanoplatelets (partially exfoliated), and 2D sheets (well-exfoliated) species in various laboratory-based and commercial dispersions of graphene and graphene oxide are identified. The high-throughput, multitasking capability of the approach to classify stacking at sub-nanometer to micrometer scale and measure the size, thickness, and concentration of exfoliated-species in generic dispersions of graphene/graphene oxide are demonstrated. The method, at its current stage, requires less than half an hour to quantitatively assess one sample of graphene/graphene oxide dispersion.


Cold plasma inactivates Salmonella Stanley and Escherichia coli O157:H7 inoculated on golden delicious apples.
Cold plasma generated in a gliding arc was applied to outbreak strains of Escherichia coli O157:H7 and Salmonella Stanley on agar plates and inoculated onto the surfaces of Golden Delicious apples. This novel sanitizing technology inactivated both pathogens on agar plates, with higher flow rate (40 liters/min) observed to be more efficacious than were lower flow rates (20 liters/min), irrespective of treatment time (1 or 2 min). Golden Delicious apples were treated with various flow rates (10, 20, 30, or 40 liters/min) of cold plasma for various times (1, 2, or 3 min), applied to dried spot inoculations. All treatments resulted in significant (P < 0.05) reductions from the untreated control, with 40 liters/min more effective than were lower flow rates. Inactivation of Salmonella Stanley followed a time-dependent reduction for all flow rates. Reductions after 3 min ranged from 2.9 to 3.7 log CFU/ml, close to the limit of detection. For E. coli O157:H7, 40 liters/min gave similar reductions for all treatment times, 3.4 to 3.6 log CFU/ml. At lower flow rates, inactivation was related to exposure time, with 3 min resulting in reductions of 2.6 to 3 log CFU/ml. Temperature increase of the treated apples was related to exposure time for all flow rates. The maximum temperature of any plasma-treated apple was 50.8 degrees C (28 degrees C above ambient), after 20 liters/min for 3 min, indicating that antimicrobial effects were not the result of heat. These results indicate that cold plasma is a nonthermal process that can effectively reduce human pathogens inoculated onto fresh produce.


[The optimal stimulation parameters of the free-field auditory steady-state responses].
Studies of the recent years are devoted to using the auditory steady-state responses (ASSR) as an evaluation method of amplification outcomes. In this case stimulation is performed in the sound field via loudspeaker with a hearing aid (HA) in patient's ear. Estimation the optimal stimulation parameters of ASSR in free field, which provide maximum correlation with behavioral thresholds. 26 subjects were included in the study: 10 with normal hearing (4 adults and 6 children) and 16 children (1-16 years old) with sensorineural hearing loss (SNHL). Aided and unaided ASSR thresholds were compared with corresponding behavioral thresholds (BT). All recordings were conducted in free sound field. We used mono-frequency stimulation method at 500-4000 Hz career frequencies. Modulation frequency was set as 40 Hz. Types of stimuli modulation: AM/FM modulation, exponential modulation (AM2), three carrier frequencies and modulated Chirp-tone (Chirp). In normal hearing subjects the difference between ASSR and BT varied from 0 dB to 35 dB, and the significant correlation between them was observed (p<0.05). The maximum difference between ASSR and BT in children with SNHL was at 500 Hz (15.6±4.3 dB), minimum - at 2 and 4 kHz (8±2.9 dB and 7±3 dB respectively). In aided condition maximum difference was detected at 500 Hz (10.2±3.8 dB), minimum - at 1 and 2 kHz (7.8±2.8 and 7.3±3.1 dB respectively). We got significantly less difference between ASSR and BT in all test conditions using following types of stimuli: at 500 Hz and 1000 Hz - AM2 (p<0.01); at 2 and 4 kHz - Chirp (p<0.05 and p<0.01 respectively). Thereby, free field ASSR might be used as an objective method of evaluation the amplification outcomes in children with SNHL.


Cytogenetic manifestations of multiple myeloma heterogeneity.
To investigate the genetic basis of the great heterogeneity observed in the clinical behavior of multiple myeloma (MM), a combined approach of G-banding, interphase fluorescence in situ hybridization (FISH), and multicolor FISH (M-FISH) was employed to analyze 70 samples from 53 patients with MM. G-banding revealed abnormal karyotypes in 77% of the cases. The origin of 31 chromosome markers was identified or revised by M-FISH. Combined metaphase karyotypic data and interphase FISH findings, using the immunoglobulin heavy-chain (IGH), IGH/cyclin D1 gene (CCND1), and D13S319 probes, revealed chromosome abnormalities in all evaluated patients and marked inter- and intratumor cytogenetic heterogeneity in the investigated MM samples. Cytogenetically unrelated clones were detected in 26% of the cases, mostly MM evaluated at diagnosis, whereas cytogenetic clonal evolution, manifested as related clones in 20% of the cases, was associated with disease progression. Among the 14q32 rearrangements, present in 66% of the cases, at least three cytogenetic subsets could be identified: one with t(11;14), usually without 13q14 deletion; another with other IGH changes, often 13q14 deletion, and hypodiploid modal chromosome number; and a third without changes in 14q32 but with abnormalities of chromosome 17. The correlation found between cytogenetic and clinicopathologic characteristics provided support for the concept that general genomic features in conjunction with specific chromosome rearrangements define the malignant phenotype in the various subsets of MM.


Evaluation of the boron tolerant grass, Puccinellia distans, as an initial vegetative cover for the Phytorestoration of a boron-contaminated mining site in Southern California.
Land damaged by boron (B) mining should be restored to its natural state with a zero net impact on biodiversity. In an earlier study (Environ. Sci. Technol.2010,44, 7089-7095), we characterized a Turkish ecotype of the grass, Puccinellia distans, which exhibited extreme tolerance to B. Here we evaluated the use of a US ecotype of P. distans as an initial vegetative cover for the phytorestoration of a B mine in southern California. Hydroponic studies revealed that this P. distans ecotype tolerated B concentrations >100 mg B/L and could be germinated and grown in B-contaminated soils taken from the sites to be restored. P. distans grew well in moderately B-contaminated soil (∼88 mg B/L saturated extract) amended with added organic matter (peat moss); other soil treatments such as gypsum addition or pH correction were not needed. P. distans also grew in severely B-contaminated soil (∼1506 mg B/L) provided that toxic levels of soil B were diluted by the addition of sand and/or organic matter. Our results provide evidence in support of the concept of using the US ecotype of P. distans as an initial vegetative cover for the phytorestoration of B-contaminated soil.


Long-term Results of Hemorrhoidal Artery Ligation.
Aim of this study is to assess the efficacy, safety, and long-term results of doppler-guided hemorrhoidal artery ligation procedure with a 7-year follow-up period for treatment of grade II and III degree hemorrhoidal diseases. The procedure was performed by a specially designed proctoscope to locate and ligate all terminal branches of superior rectal artery. Patients were followed up at postoperative 1st week and 3rd, 12th, and 24th months by physical examination and 7th year by phone questionnaire using Short Form-36. Between November 2006 and May 2007, 50 patients (29 females, mean age = 38.2) underwent this procedure. All patients discharged at operation day and mean return to work was 2.5 days. There were no major complications and mean postoperative Visual Analogous Scale at first week was 1.72. At 24th month, 44 (88%) and 38 (76%) patients at 7th year were symptom free. Doppler-guided hemorrhoidal artery ligation is a safe, effective, and outpatient procedure, which can be the treatment of choice for second- and third-degree hemorrhoidal diseases with satisfactory long-term results.


Effectiveness of the LigaSure Small Jaw Vessel-Sealing System in Hepatic Resection.
In hepatic resection for liver tumors, reducing operation time and blood loss are important for postsurgical complication prevention. This study aimed to compare the safety and efficacy of the LigaSure Small Jaw (Covidien, Boulder, CO) with those of the Cavitation Ultrasonic Surgical Aspirator (CUSA) system (Integra Life Sciences, Plainsboro, NJ) in hepatic surgery. We enrolled 102 patients with liver tumors, of whom 51 underwent liver resection with the CUSA (CUSA group) between March 2004 and April 2011. Another 51 underwent resection with the LigaSure Small Jaw (LS group) between June 2011 and July 2012. We stratified patients by time period depending on the instrument used, and compared operative duration; intraoperative bleeding; and postoperative liver function and complication rate. Total operation time (mean ± SD) was significantly shorter in the LS group than in the CUSA group (358.8 ± 91.7 versus 460.6 ± 146.1 min, P < 0.001). Blood loss was not significantly different between the 2 groups. Frequency of postoperative complications was lower, but not significantly, in the LS group. The LigaSure Small Jaw may allow a shorter total operative duration than the CUSA device.


Quantitative Analysis of Human Corneal Lenticule Surface Microstructure Irregularity with 3D Optical Profiler Using White Light Interferometry.
To quantitatively evaluate the cutting quality of small incision lenticule extraction (SMILE) by measuring human corneal lenticule surface roughness in different areas with white light interferometer. A white light interferometer was used to quantitatively measure the corneal lenticule surface roughness in different areas. Sixty-three myopic patients (102 eyes) who underwent SMILE surgery were recruited. The surface roughness of the central, pericentral, and peripheral parts of the corneal lenticule surface was measured in both the anterior and posterior planes. Differences in corneal lenticule surface roughness were analyzed between different myopic groups. The surface roughness of the anterior plane of the corneal lenticule was lower than the posterior plane in various areas (central, pericentral, and peripheral parts) (P < .01). Surface roughness gradually increased from the center to the periphery, in both the anterior and posterior planes (P < .01). There were no significant differences in the surface roughness of the central part in both the anterior and posterior planes between the low and high myopic groups. The surface roughness of the high myopic group was higher than that of the low myopic group in the peripheral part (P < .01). There were no significant differences among the three cylinder-specific groups. There was no significant correlation between two paired eyes. A positive correlation between posterior central surface roughness and the percentage tissue altered score (PTA) was found (r = 0.248, P = .012). The cutting surface of the corneal lenticule performed by femtosecond laser was evaluated with a white light interferometer and displayed inhomogeneity. Deeper cutting with higher myopia and some intraoperative complications, such as suction loss, may result in larger irregularities.


Prevalence of falls in elderly in Brazil: a countrywide analysis.
We conducted a cross-sectional study of a sample of 6,616 elderly living in urban areas of 100 municipalities in 23 Brazilian states, who responded to questions on the occurrence of falls in the 12 months prior to the interview, and occurrence of fractures due to the falls. The prevalence of falls among the elderly was 27.6% (95%CI: 26.5-28.7). Among those reporting falls, 11% had suffered fractures as a result. Of the elderly, 36% had received guidance about the precautions necessary to prevent falls, and about 1% had required surgery. Falls were associated with female gender, older age, low socioeconomic status, obesity and sedentary lifestyles. The prevalence of falls differed significantly between the North and other regions of Brazil. The study shows a high prevalence of falls, and underlines the need for preventive strategies targeting modifiable risk factors.


Sonography of the anterior abdominal wall.
The improved penetrating power of high frequency, high resolution transducers has made possible routine examination of the anterior abdominal wall. Over 2 years, 79 abdominal wall examinations were performed and the results compared with anatomic findings at surgery. The abdominal wall may be divided into three sonographically distinct regions: the midline, the paramedian, and the inguinal regions. Normal structures can be seen in relation to constant landmarks, and disruption of normal architecture identified.


Reliable pre-eclampsia pathways based on multiple independent microarray data sets.
Pre-eclampsia is a multifactorial disorder characterized by heterogeneous clinical manifestations. Gene expression profiling of preeclamptic placenta have provided different and even opposite results, partly due to data compromised by various experimental artefacts. Here we aimed to identify reliable pre-eclampsia-specific pathways using multiple independent microarray data sets. Gene expression data of control and preeclamptic placentas were obtained from Gene Expression Omnibus. Single-sample gene-set enrichment analysis was performed to generate gene-set activation scores of 9707 pathways obtained from the Molecular Signatures Database. Candidate pathways were identified by t-test-based screening using data sets, GSE10588, GSE14722 and GSE25906. Additionally, recursive feature elimination was applied to arrive at a further reduced set of pathways. To assess the validity of the pre-eclampsia pathways, a statistically-validated protocol was executed using five data sets including two independent other validation data sets, GSE30186, GSE44711. Quantitative real-time PCR was performed for genes in a panel of potential pre-eclampsia pathways using placentas of 20 women with normal or severe preeclamptic singleton pregnancies (n = 10, respectively). A panel of ten pathways were found to discriminate women with pre-eclampsia from controls with high accuracy. Among these were pathways not previously associated with pre-eclampsia, such as the GABA receptor pathway, as well as pathways that have already been linked to pre-eclampsia, such as the glutathione and CDKN1C pathways. mRNA expression of GABRA3 (GABA receptor pathway), GCLC and GCLM (glutathione metabolic pathway), and CDKN1C was significantly reduced in the preeclamptic placentas. In conclusion, ten accurate and reliable pre-eclampsia pathways were identified based on multiple independent microarray data sets. A pathway-based classification may be a worthwhile approach to elucidate the pathogenesis of pre-eclampsia.


CCL21-induced calcium transients and proliferation in primary mouse astrocytes: CXCR3-dependent and independent responses.
CCL21 is a homeostatic chemokine that is expressed constitutively in secondary lymph nodes and attracts immune cells via chemokine receptor CCR7. In the brain however, CCL21 is inducibly expressed in damaged neurons both in vitro and in vivo and has been shown to activate microglia in vitro, albeit not through CCR7 but through chemokine receptor CXCR3. Therefore, a role for CCL21 in CXCR3-mediated neuron-microglia signaling has been proposed. It is well established that human and mouse astrocytes, like microglia, express CXCR3. However, effects of CCL21 on astrocytes have not been investigated yet. In this study, we have examined the effects of CCL21 on calcium transients and proliferation in primary mouse astrocytes. We show that similar to CXCR3-ligand CXCL10, CCL21 (10(-9) M and 10(-8) M) induced calcium transients in astrocytes, which were mediated through CXCR3. However, in response to high concentrations of CCL21 (10(-7) M) calcium transients persisted in CXCR3-deficient astrocytes, whereas CXCL10 did not have any effect in these cells. Furthermore, prolonged exposure to CXCL10 or CCL21 promoted proliferation of wild type astrocytes. Although CXCL10-induced proliferation was absent in CXCR3-deficient astrocytes, CCL21-induced proliferation of these cells did not significantly differ from wild type conditions. It is therefore suggested that primary mouse astrocytes express an additional (chemokine-) receptor, which is activated at high CCL21 concentrations.


Pharmacological modulation of functional connectivity: α2-adrenergic receptor agonist alters synchrony but not neural activation.
Correlative low frequency fluctuations in functional MRI (fMRI) signals across brain regions at rest have been taken as a measure of functional connectivity to map large-scale neural networks; however, the neural origin is still not clear. Receptor-targeted pharmacological manipulation could elucidate the role of neuroreceptor systems in resting-state functional connectivity to provide another perspective on the mechanism. In this study, the dose-dependent effects of an α(2)-adrenergic receptor agonist, medetomidine, on brain activation and functional connectivity were investigated. Forepaw stimulation-induced activation and resting-state fluctuation in the rat somatosensory cortices and caudate putamen were measured using the blood oxygenation level dependent (BOLD) fMRI. The results showed significant dose-dependent suppression of inter-hemispheric correlation but not the amplitude in the somatosensory areas, while the stimulation-induced activation in the same areas remained unchanged. To clarify the potential change in the hemodynamic response caused by the vasoconstrictive effect of medetomidine, the resting perfusion fluctuation was studied by arterial spin labeling and showed similar results as the BOLD. This suggests that the oxygen metabolic rate and hence the neural activity may not be affected by medetomidine but only the synchrony between brain regions was suppressed. Furthermore, no change in functional connectivity with medetomidine dosages was seen in the caudate putamen, a region with much lower α(2)-receptor density. These results indicate that resting-state signal correlation may reflect underlying neuroreceptor activity and a potential role of the adrenergic system in the functional connectivity.


[Late symptoms among patients surgically treated for breast cancer. A questionnaire in the county of Southern Jutland].
The 1989 protocol of the Danish Breast Cancer Cooperative Group implied a more extensive axillary dissection and reduced frequency of regional lymphnode irradiation. A questionnaire concerning late symptoms was sent to all women operated from 1989 to 1993. The rate of response among women treated with modified radical mastectomy was 82%. Of 163 patients, 79% had one or more late symptoms. Most troublesome was pain in the neck, shoulder and arm or scar-related pain. Other symptoms were lymphoedema, paraesthesia of the arm and impaired shoulder function; each symptom occurring among 29-47% of the women. Most symptoms began three to four weeks postoperatively. The frequency of late symptoms corresponded with number of lymphnodes removed, number of tumourpositive nodes and irradiation of the scar. Thirty-five women were treated with tumourectomy and they experienced similar late symptoms with a similar degree of distress. It is concluded that late symptoms among women treated for breast cancer still occur frequently.


Retinoic acid restores the levels of cellular cholesterol in Leishmania donovani infected macrophages by increasing npc1 and npc2 expressions.
Visceral leishmaniasis (VL) is a fatal form among all forms of leishmaniasis and is caused by visceralization of the Leishmania donovani (Ld) parasite to the critical organs. Mild to severe malnutrition is common in VL patients and the deficiency of retinoic acid (RA), an important micronutrient, results in a compromised state of immune response in macrophages (mφ) leading to the increased parasite load. In the continuation of our earlier work, we observed loss of cellular cholesterol in infected mφ in the absence of RA i.e., upon inhibition of RALDH pathway. Moreover, the Leishmania utilizes host cholesterol for the establishment of infection and causes a decrease in the expressions of Niemann-Pick C2 (npc2) and Niemann-Pick C1 (npc1) genes involved in the uptake of extracellular cholesterol. This results in reduced levels of cellular cholesterol in infected mφ. Intrigued by this, as the first sign of our hypothesis, we investigated the presence of RA Response Element (RARE) sequences in the upstream of npc1 and npc2 genes. To functionally confirm this, we measured their expressions and the levels of cellular cholesterol in Ld infected mφ in the absence (i.e., using an inhibitor of RALDH pathway) and presence of RA. We found restoration of the levels of cellular cholesterol in infected mφ under the supplementation of RA resulting in the decreased parasite load. Hence, the supplementation of RA with the standard therapy and/or preventive use of RA could be potentially an advancement in the treatment and cure of VL patients.


Predicting expressive vocabulary acquisition in children with intellectual disabilities: a 2-year longitudinal study.
This study's objectives were to describe expressive vocabulary acquisition in children with intellectual disabilities (ID) and to examine specific pre- and early linguistic behaviors used to request and comment, chronological age, cognitive skills, and vocabulary comprehension as predictors of expressive vocabulary. This study included 36 children with ID, age 3;00 (years;months) to 6;05, with an average initial expressive vocabulary of 67 words. Expressive vocabulary acquisition was longitudinally followed over a 2-year period based on 4-monthly administrations of the Dutch version of the MacArthur Communicative Development Inventory/Words and Gestures (I. Zink & M. Lejaegere, 2002). Specific pre- and early linguistic behaviors used to request and comment as well as cognitive skills and vocabulary comprehension were measured at baseline. Individual growth modeling indicated that vocabulary comprehension was the only unique predictor of initial expressive vocabulary. Subsequent vocabulary growth was uniquely predicted by proportion of bimodal gesture + vocalization comments, chronological age, and cognitive skills. The results of this study underscore the great heterogeneity in expressive vocabulary skills in children with ID. The importance of prelinguistic communication, chronological age, cognitive skills, and vocabulary comprehension for explaining differences in expressive vocabulary skills is discussed.


[A case of pathologic (F63.0) or dangerous (Z72.6) gambling?].
The authors recapitulate the term of pathological gambling in different classifications incl. the 10th revision of the ICD. It is a new concept which involves certain obscure points also from the linguistic aspect. They demonstrate on a forensic expert opinion elaborated by the Faculty why the statement of the accused that he committed extensive property offenses as a result of pathological gambling was not accepted by experts.


"Early" apoplexy due to traumatic intracranial aneurysm--case report.
A 76-year-old man presented with a traumatic aneurysm of the left internal carotid artery which caused repeated subarachnoid hemorrhages within 20 hours of a fall from a height. Early computed tomography (CT) detected no brain abnormalities, but repeat CT found subarachnoid hemorrhage. Internal carotid angiography detected a pseudoaneurysm, which was not treated because of his poor clinical condition. He died of multiple organ failure. Early detection of a traumatic intracranial aneurysm is important for the prevention of aneurysmal rupture, or "delayed" apoplexy. Review of 171 cases with traumatic aneurysms from the literature found that false negative angiography occurred only in three cases on post-trauma day 7 and thereafter. Early diagnostic angiography within a week of the initial trauma is indicated if traumatic aneurysm is suspected to detect early signs of irregularity, spasm, and narrowing of the arterial wall. Repeat angiography is indicated if aneurysmal formation is still highly suspected in spite of negative initial angiography.


Diagnostic and prognostic value of the peripheral natural killer cell levels in gastric cancer.
Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3+, CD4+ and CD8+ T lymphocytes, B cells (CD19+), regulatory T cells (Tregs; CD4+CD25+CD127-) and natural killer (NK) cells (CD3-CDl6+CD56+) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56+) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC.


Resistance to chloroquine therapy in pregnant women with malaria parasitemia.
The objective of the study was to determine the efficacy of chloroquine in pregnant women with Plasmodium falciparum parasitemia at therapeutic doses of 25 mg/kg body weight divided over 3 days. Three-hundred pregnant women in Kilifi Hospital at the coast of Kenya were screened for malaria parasitemia using Giemsa stained thick blood smears. In vivo and in vitro parasite sensitivity to chloroquine was determined. P. falciparum infections were present in 65 (22%) of 300 pregnant women. The in vivo tests showed that 46% of all the P. falciparum infections were resistant to chloroquine predominantly at RI and RII levels. The in vitro tests showed a resistance rate of 35%. A large proportion of pregnant women with malaria do not respond to chloroquine therapy and alternative drugs are required.


Conservation of energy, uncertainty reduction, and swift utilization of medical care among the elderly: study II.
This study examined age differences in the timing of the decision to seek medical care. The data were obtained from a longitudinal study of 366 community dwelling adults aged 45 to 93 years. Subjects were paired for age, gender, and health status, and both members of a pair were interviewed when either one initiated a medical visit for a new problem. This allowed the authors to examine delay in care-seeking for individuals with new symptoms who did not seek care as well as those who did. Survival analysis was used to test hypotheses respecting age differences for total delay (the time from first noticing symptoms until calling for care) and its two constituent phases: appraisal delay (symptom onset until deciding one was ill) and illness delay (decision one was ill until calling for care). Older persons were expected to be more avoidant of uncertainty and conserving of physical and psychic resources and thus quicker to seek care. The results and findings on reasons for delay support the uncertainly avoidance hypothesis but did not replicate signs of higher levels of avoidance behavior by middle-aged subjects than by older subjects.


Effect of macromolecular crowding on DNA:Au nanoparticle bioconjugate assembly.
DNA:Au nanosphere bioconjugates have applications in biosensing and in the bottom-up assembly of materials. These bioconjugates can be selectively assembled into three-dimensional aggregates upon addition of complementary DNA oligonucleotides and can be dissociated by heating above a melting transition temperature at which the DNA duplexes are denatured. Herein we describe the impact of polymeric solutes on the thermal denaturation behavior of DNA:Au nanoparticle bioconjugate assemblies. Polymeric solutes can dramatically impact biochemical reactions via macromolecular crowding. Poly(ethylene glycol)s (PEGs) and dextrans of varying molecular weights were used as crowding reagents. While both PEG and dextran increased the stability of DNA:Au aggregates, melting transition temperatures in the presence of PEG were impacted more significantly. Polymer molecular weight was less important than polymer chemistry and weight percent in solution. For a high (15%) weight percent of PEG, aggregation was observed even in the absence of complementary oligonucleotides. These results underscore the importance of polymer chemistry in addition to physical volume exclusion in macromolecular crowding and point to the importance of understanding these effects when designing biorecognition-based nanoparticle assembly schemes in complex matrixes (i.e., any involving polymeric solutes).


Effects of chronic metabolic acidosis on splanchnic protein turnover and oxygen consumption in human beings.
Although metabolic acidosis stimulates protein catabolism, its effects on splanchnic protein turnover and energy expenditure have not been measured in human beings. We investigated the effects of chronic metabolic acidosis (CMA) on splanchnic protein dynamics and oxygen consumption in human beings by using a leucine tracer and mass-balance techniques. Five subjects were studied after 6 days of HCl-, CaCl(2)-, and NH(4)Cl-induced acidosis; 8 subjects served as controls. Blood samples were collected from the radial artery and the hepatic veins. Measurements were performed on plasma and whole-blood samples. Based on plasma measurements, subjects who had undergone CMA had lower rates of splanchnic proteolysis (-35%) and protein synthesis (-50%; P < .05) than controls, as well as a negative leucine kinetic balance (-6.81 +/- 2.48 micromol/kg/min/1.73 m(2) body surface [BS](-1)), compared with the neutral balance in control plasma samples (0.76 +/- 2.11 micromol/kg/min/1.73; P < .05 between groups). Based on measurements from whole blood, splanchnic proteolysis and protein synthesis did not differ significantly between CMA and control samples, and the net leucine kinetic balance was neutral in both groups (CMA, -0.69 +/- 1.57; controls, -0.74 +/- 3.45 micromol/kg/min/1.73). In CMA whole-blood measurements, splanchnic oxygen consumption (44.8 +/- 4.3 mL/min/1.73 m(2) BS) was slightly lower than in controls (57.5 +/- 8.4 mL/min/1.73 m(2) BS; P = NS). Splanchnic protein synthesis correlated with oxygen consumption (r = 0.82; P < .001). CMA reduces splanchnic protein turnover and results in a negative leucine balance--an effect that apparently is offset by the contribution of blood cells to organ leucine (and protein) dynamics. Protein synthesis is a major contributor (about 67%) to energy expenditure in splanchnic organs.


Computation of ionic distributions around charged biomolecular structures: results for right-handed and left-handed DNA.
We introduce an efficient computational methodology employing the potentials of mean force approach for estimating the detailed three-dimensional ionic distributions around arbitrarily complex charged biomolecular structures for all monovalent salt concentrations of practical interest (e.g., 0.1-5.0 M NaCl). Such distributions are required for specifying thermodynamic and structure-specific features of ion-mediated interactions of charged proteins, DNA and RNA, membranes, and macromolecular assemblies. As a first application, we present results for distributions around the B and ZI conformers of the DNA oligomer d(C-G)18.d(C-G)18. The ionic microenvironment depends strongly on the DNA conformation, sequence, and bulk salt concentrations.