Design and optimization of metformin hydrophobic ion pairs for efficient encapsulation in polymeric drug carriers.
Loading small molecular weight hydrophilic drugs into polymeric carriers is a challenging task. Metformin hydrochloride (MET) is a highly soluble oral antidiabetic drug of small size and high cationic charge. Hydrophobic ion pairing (HIP) is an approach for reversible modulation of solubility and hydrophilicity of water-soluble drugs via complexation with oppositely charged molecules. Herein, we prepared MET ion pairs and carefully studied and characterized MET interaction with different ligands, with the aim of increasing MET lipophilicity and loading efficiency. HIP was successful using three hydrophilic anionic ligands; sodium dodecyl sulphate (SDS) Carbopol (CB) and tannic acid (TA). Electrostatic interaction and hydrogen bonding drove the complexation per spectroscopic and thermal studies. Complexation efficiency depended on ligand type and charge ratio. While complexes had varying interaction strengths, the excessive stability of TA/MET resulted in unfavorable poor MET dissociation. Notably, HIP imparted a 450 and tenfold lipophilicity increase for SDS/MET and CB/MET, respectively. The latter showed favorable controlled, yet complete release of MET at pH 6.8 and was loaded into alginate beads. Complex bulkiness and decreased lipophilicity resulted in a dramatic 88% increase of MET loading, demonstrating the success of HIP as a simple, efficient and applicable approach for modulating drug's properties.


Effect of pupil dilation on biometry measurements and intraocular lens power in eyes with high myopia.
The present study sought to evaluate the effects of pupil dilation on ocular parameter measurements and intraocular lens (IOL) power calculation using IOLMaster in highly myopic cataract patients. A total of 233 eyes were included in this prospective study and assigned to four groups based on range of axial length (AL) as follows: group A:26-28 mm, group B:28-30 mm, group C:30-32 mm, and group D:32-36 mm. Flattest and steepest keratometry (K1 and K2), AL, anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WtW) were determined using IOLMaster before and after administration of topical tropicamide. The corresponding IOL powers were calculated using Sanders-Retzlaff-Kraff/theoretical (SRK/T), Haigis, and Barrett Universal II formulas. Variations in AL, K1 and K2 following dilation were not significant (P > 0.05 in all groups). The results showed that ACD increased significantly after dilation (P = 0.000 in all groups), whereas LT decreased significantly after dilation (P = 0.000, 0.000, 0.001, and 0.003). Post-dilation WtW increased significantly in Group A, B, and C (P = 0.001, 0.001, and 0.025) but not in Group D. When IOL power was calculated as a discrete variable, significant differences were observed between pre- and post-dilation IOL power. Pupil dilation in cataract eyes with high myopia does not cause significant changes in AL and K. However, it significantly increases ACD as well as WtW values and significantly decreases the LT value. Surgeons should evaluate the effect of pupil dilation on IOL power prediction as the present findings show extreme cases. Notably, Barrett Universal II formula had the best concordance between different pupil conditions in long eyes.


Trust in the approval process of medicines mediates the effect of an educational intervention on the pain relief induced by a generic analgesic.
Generic medicines have been associated with less efficacy compared to originator products. Educational videos explaining generic medicines can have a positive effect on perceptions of generic drugs and their pain-relieving effect. The central aim of the current study was to examine whether trust in the governmental approval process of medicines mediates the effect of educational video interventions on the pain-relieving effect induced by a generic medicine and whether trust can be built by improving individuals' understanding of generic medication. This is a secondary analysis of a randomized controlled trial where participants with frequent tension headaches were randomly assigned to either watching a video explaining generic drugs (n = 69) or a video informing about headaches (control group: n = 34). After watching the video, participants took an originator and a generic pain analgesic in a randomized order to treat their next two consecutive headaches. Pain severity was measured before and 1 h after taking the medicine. A multiple serial mediator model showed that improving individuals' understanding of generic medicines is associated with increased trust in medicines. Both factors together, understanding and trust, significantly mediated the effect of the video education about generic drugs on the generic's pain-relieving effect (total indirect effect: coefficient: 0.20, 95% CI: 0.42, -0.0001). Results of this study show that improving individuals' understanding of generic medication and trust in the process of approving medicines should be considered as important mechanisms of future educational interventions about generic medicines.


The impact of myocardial fibrosis biomarkers in a heart failure population with atrial fibrillation-The HARVEST-Malmö study.
Several studies suggest that circulating biomarkers of myocardial fibrosis are associated with worse prognosis in subjects with atrial fibrillation (AF). Here, we aimed to explore associations between fibrosis biomarkers, prevalent AF, and left atrial volume (LAV) enlargement in subjects with heart failure (HF). Additionally, we evaluated the prognostic impact of fibrotic biomarkers in HF with co-existing AF. Patients hospitalized for HF (n = 316, mean age 75 years; 30% women) were screened for AF. Seven proteins previously associated with myocardial fibrosis [metalloproteinase inhibitor 4 (TIMP-4), suppression of tumorigenicity 2 (ST-2), galectin-3 (GAL-3), growth/differentiation factor-15 (GDF-15), and matrix metalloproteinase 2, 3, and 9 (MMP-3, MMP-3, and MMP-9, respectively)] were analyzed using a proximity extension assay. Proteins with significant Bonferroni-corrected associations with mortality and re-hospitalization risk were taken forward to multivariable Cox regression analyses. Further, Bonferroni-corrected multivariable logistic regression models were used to study associations between protein plasma levels, prevalent AF, and severely enlarged left atrial volume index (LAVI ≥ 48 ml/m2). Prevalent AF was observed in 194 patients at the hospitalization of whom 178 (92%) were re-hospitalized and 111 (57%) died during the follow-up period. In multivariable logistic regression models, increased plasma levels of TIMP-4, GDF-15, and ST-2 were associated with the prevalence of AF, whereas none of the seven proteins showed any significant association with severely enlarged LAVI. Increased plasma levels of five proteins yielded significant associations with all-cause mortality in patients with co-existing AF; TIMP-4 (HR 1.33; CI95% 1.07-1.66; p = 0.010), GDF-15 (HR 1.30; CI95% 1.05-1.62; p = 0.017), GAL-3 (HR 1.29; CI95% 1.03-1.61; p = 0.029), ST-2 (HR 1.48; CI95% 1.18-1.85; p < 0.001), and MMP-3 (HR 1.33; CI95% 1.09-1.63; p = 0.006). None of the proteins showed any significant association with re-hospitalization risk. In this study, we were able to demonstrate that elevated levels of three plasma proteins previously linked to myocardial fibrosis are associated with prevalent AF in a HF population. Additionally, higher levels of five plasma proteins yielded an increased risk of mortality in the HF population with or without co-existing AF.


Recovery of nickel and preparation of ferronickel alloy from spent petroleum catalyst via cooperative smelting-vitrification process with coal fly ash.
Spent petroleum catalyst (SPC) is a highly toxic material since it contains heavy metals and hazardous substances. A novel recycling technology based on the cooperative smelting-vitrification process by using coal fly ash (CFA) as a fluxing material was proposed. The benefits of employing CFA in this cooperative smelting-vitrification process of SPC have been demonstrated via the results of lab-scale and scale-up experiments. The experimental results indicated that with a collector iron (Fe) addition of 26 wt%, a C/O molar ration of 1.4, and an H3BO3 addition of 14 wt%, the maximum nickel (Ni) recovery was ∼98% by controlling the CFA addition of 40-50 wt%, basicity of 0.4-0.5, smelting temperature of 1550°C, and smelting time of 60 min, respectively. In this process, a ferronickel (Ni-Fe) alloy with a high Ni grade of 10 wt% was successfully obtained, which could be directly further produced stainless steel. Meanwhile, a glass slag with a low Ni content (below 0.12 wt%) was also obtained, and its leaching characteristics further confirmed it is a non-hazardous slag because heavy metals were successfully encapsulated in glass slag, and thereby, this proposed method achieved the transformation from hazardous solid waste to general solid waste. The results of the 10 kg scale-up experiment indicated the possibility of industrialization of this new technology. Therefore, the process proposed in this study is a practical and promising process for Ni recovery from SPC and reutilization of CFA.


Hybrid intravascular imaging: current applications and prospective potential in the study of coronary atherosclerosis.
The miniaturization of medical devices and the progress in image processing have allowed the development of a multitude of intravascular imaging modalities that permit more meticulous examination of coronary pathology. However, these techniques have significant inherent limitations that do not allow a complete and thorough assessment of coronary anatomy. To overcome these drawbacks, fusion of different invasive and noninvasive imaging modalities has been proposed. This integration has provided models that give a more detailed understanding of coronary artery pathology and have proved useful in the study of the atherosclerotic process. In this review, the authors describe the currently available hybrid imaging approaches, discuss the technological innovations and efficient algorithms that have been developed to integrate information provided by different invasive techniques, and stress the advantages of the obtained models and their potential in the study of coronary atherosclerosis.


Percepts evoked by multi-electrode stimulation of human visual cortex.
Direct electrical stimulation of early visual cortex evokes the perception of small spots of light known as phosphenes. Previous studies have examined the location, size, and brightness of phosphenes evoked by stimulation of single electrodes. While it has been envisioned that concurrent stimulation of many electrodes could be used as the basis for a visual cortical prosthesis, the percepts resulting from multi-electrode stimulation have not been fully characterized. To understand the rules governing perception of phosphenes evoked by multi-electrode stimulation of visual cortex. Multi-electrode stimulation was conducted in human epilepsy patients. We examined the number and spatial arrangement of phosphenes evoked by stimulation of individual multi-electrode groups (n = 8), and the ability of subjects to discriminate between the pattern of phosphenes generated by stimulation of different multi-electrode groups (n = 7). Simultaneous stimulation of pairs of electrodes separated by greater than 4 mm tended to produce perception of two distinct phosphenes. Simultaneous stimulation of three electrodes gave rise to a consistent spatial pattern of phosphenes, but with significant variation in the absolute location, size, and orientation of that pattern perceived on each trial. Although multi-electrode stimulation did not produce perception of recognizable forms, subjects could use the pattern of phosphenes evoked by stimulation to perform simple discriminations. The number of phosphenes produced by multi-electrode stimulation can be predicted using a model for spread of activity in early visual cortex, but there are additional subtle effects that must be accounted for.


Stereological analyses of reward system nuclei in maternally deprived/separated alcohol drinking rats.
The experience of early life stress can trigger complex neurochemical cascades that influence emotional and addictive behaviors later in life in both adolescents and adults. Recent evidence suggests that excessive alcohol drinking and drug-seeking behavior, in general, are co-morbid with depressive-like behavior. Both behaviors are reported in humans exposed to early life adversity, and are prominent features recapitulated in animal models of early life stress (ELS) exposure. Currently, little is known about whether or how ELS modulates reward system nuclei. In this study we use operant conditioning of rats to show that the maternal separation stress (MS) model of ELS consumes up to 3-fold greater quantities of 10% vol/vol EtOH in 1-h, consistently over a 3-week period. This was correlated with a significant 22% reduction in the number of dopaminergic-like neurons in the VTA of naïve MS rats, similar to genetically alcohol-preferring (P) rats which show a 35% reduction in tyrosine hydroxylase (TH)-positive dopaminergic neurons in the VTA. MS rats had a significantly higher 2-fold immobility time in the forced swim test (FST) and reduced sucrose drinking compared to controls, indicative of depressive-like symptomology and anhedonia. Consistent with this finding, stereological analysis revealed that amygdala neurons were 25% greater in number at P70 following MS exposure. Our previous examination of the dentate gyrus of hippocampus, a region involved in encoding emotional memory, revealed fewer dentate gyrus neurons after MS, but we now report this reduction in neurons occurs without effect on the number of astrocytes or length of astrocytic fibers. These data indicate that MS animals exhibit neuroanatomical changes in reward centers similar to those reported for high alcohol drinking rats, but aspects of astrocyte morphometry remained unchanged. These data are of high relevance to understand the breadth of neuronal pathology that ensues in reward loci following ELS.


Evaluation of the genotoxicity of the imidazole antifungal climbazole: comparison to published results for other azole compounds.
Climbazole is an imidazole antifungal agent that can provide anti-dandruff benefits when incorporated into a shampoo matrix. A series of genotoxicity studies were performed to support the human safety of this azole antifungal drug. Climbazole was not mutagenic in the Salmonella typhimurium or Escherichia coli Ames assay and did not induce micronuclei in human lymphocytes. In the mouse lymphoma assay (MLA), climbazole was negative (non-mutagenic) with and without metabolic (S9) activation after a 4 h exposure; an increase in small colony mutants was observed without metabolic activation after a 24 h exposure at concentrations of 15 and 17.5 μg/mL. An in vivo mouse micronucleus test was negative up to a maximum tolerated dose (MTD) of 150 mg/kg climbazole administered orally. In the in vivo/in vitro unscheduled DNA synthesis assay, climbazole showed no evidence of DNA damage in the livers of rats at doses up to the MTD of 200 mg/kg orally. A toxicokinetic study was performed in mice with oral administration of [14C]-climbazole (150 mg/kg). Radioactivity (20.42 μg-equiv./g plasma) was detected 15 min after oral administration of [14C]-climbazole, and the peak concentration was 62.96 μg-equiv./g plasma at 8 h after dosing. The measured amounts of radioactivity in plasma, at all sample times from 15 min up to 24 h, exceeded the concentrations that induced increases in mutation frequency after 24 h exposure of mouse lymphoma cells in vitro (15 and 17.5 μg/mL). These observations lend support to the conclusion that climbazole does not present a genotoxic risk in vivo. Furthermore, these data are consistent with the published data for other azole antifungals that work by preventing the synthesis of ergosterol and, as a class, are generally non-genotoxic, except some isolated positive results of questionable significance. Collectively, these data are supportive of the view that climbazole does not present a genotoxic or carcinogenic risk to humans.


The "edge effect" with patch test materials.
A positive "edge effect", i.e., the accumulation on the skin of a chemical solution (such as fluorescein 0.01% in a 50/50 water-ethanol solution) at the periphery of the patch test sites has been demonstrated. It occurs with different test materials (Finn Chamber; Silver Patch Test; Patch Test Chamber). Practical implications are discussed: this observation could be important when discussing results of laboratory investigations. In clinical practice, it could explain the occurrence of "ring-shaped" positive allergic patch test reactions to chemicals used in solution, i.e., Kathon CG or hydrocortisone.


PCR-RFLP analysis of the IGS region of rDNA: a useful tool for the practical discrimination between species of the genus Debaryomyces.
The amplification by PCR of the intergenic spacer region (IGS) of rDNA followed by restriction fragment length polymorphism (RFLP) analysis was evaluated as a potential method for discriminating the 16 species belonging to the genus Debaryomyces. The digestion of this region with some or all the enzymes used in this study (HapII, HhaI and MboI) produced species-specific patterns that permitted differentiation of the species in the genus. With the exception of Debaryomyces vanrijiae, the technique was also efficient for distinguishing the varieties in the species Debaryomyces hansenii (var. hansenii, var. fabryi), Debaryomyces occidentalis (var. occidentalis, var. persoonii) and Debaryomyces polymorphus (var. africanus, var. polymorphus), respectively. PCR-RFLP analysis of the IGS region of rDNA is proposed as a clear and reproducible technique for the practical discrimination of species of the yeast genus Debaryomyces.


Hyaluronic acid-based M1 macrophage targeting and environmental responsive drug releasing nanoparticle for enhanced treatment of rheumatoid arthritis.
Herein, hyaluronic acid (HA) and β-cyclodextrin (β-CD) is used to form targeted drug delivery platform HCPC/DEX NPs with previously prepared carbon dots (CDs) as cross-linker, dexamethasone (DEX) is loaded for rheumatoid arthritis (RA) treatment. The drug loading capacity of β-CD and M1 macrophage targeting of HA were utilized for efficient delivery of DEX to the inflammatory joints. Because of the environmental responsive degradation of HA, DEX can be released in 24 h and inhibit the inflammatory response in M1 macrophages. The drug loading of NPs is 4.79 %. Cellular uptake evaluation confirmed that NPs can specifically target to M1 macrophages via HA ligands, the uptake of M1 macrophages is 3.7 times that of normal macrophages. In vivo experiments revealed that NPs can accumulate in RA joints to alleviate inflammation and accelerate cartilage healing, the accumulation can be observed in 24 h. The cartilage thickness increased to 0.45 mm after HCPC/DEX NPs treatment, indicating its good RA therapeutic effect. Importantly, this study was the first to utilize the potential acid and reactive oxygen species responsiveness of HA to release drug and prepare M1 macrophage targeting nanodrug for RA treatment, which provides a safe and effective RA therapeutic strategy.


Evaluation of practice change in Tanzanian health professionals 12 months after participation in an Infection Prevention and Management Course.
Hospital-acquired infection (HAI) is a problem confronting developing countries. Education programmes have been shown to be effective in increasing awareness and changing practice in health professionals. Practice change in health professionals who completed an Infection Prevention and Management Course in Tanzania was explored via focus group 12 months after completion of the course. Positive changes in infection control practice were found, along with barriers to more widespread change. Providing tailored and continuing education programs to hospital staff, including managers, is recommended.


Opportunities and challenges of translational 3D bioprinting.
3D-printed orthopaedic devices and surgical tools, printed maxillofacial implants and other printed acellular devices have been used in patients. By contrast, bioprinted living cellular constructs face considerable translational challenges. In this Perspective, we first summarize the most recent developments in 3D bioprinting for clinical applications, with a focus on how 3D-printed cartilage, bone and skin can be designed for individual patients and fabricated using the patient's own cells. We then discuss key translational considerations, such as the need to ensure close integration of the living device with the patient's vascular network, the development of biocompatible bioinks and the challenges in deriving a physiologically relevant number of cells. Lastly, we outline untested regulatory pathways, as well as logistical challenges in material sourcing, manufacturing, standardization and transportation.


Decline in the incidence of healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) correlates with deceased antimicrobial consumption at a tertiary care hospital in Taiwan, 2001-2009.
The present study investigated the long-term impact of antibiotic use policy on the rates of consumption (expressed as daily-defined doses/1000 patient-days) of various parenteral antibiotics and on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and the incidence of healthcare-associated MRSA (HA-MRSA) infection at a tertiary care hospital from 2001 to 2009. During this time, consumption of all antimicrobials for systemic use decreased by 33%. This change was driven by a 44% decrease in the consumption of unrestricted antibacterials, which was offset by a 42% increase in the consumption of restricted agents. The trends in MRSA prevalence (number of isolates/1000 patient-days) and HA-MRSA incidence (number of HA-MRSA-infected persons/1000 patient-days) correlated with the trend in overall consumption of antimicrobials. Significant positive correlations were observed between MRSA prevalence and the consumption of extended-spectrum and β-lactamase-resistant penicillins, first-generation cephalosporins, macrolides, lincosamides and streptogramins, aminoglycosides, and glycopeptides. Significant positive correlations were found between the incidence of HA-MRSA infection and the consumption of tetracyclines, extended-spectrum and β-lactamase-resistant penicillins, sulfonamides and trimethoprim, macrolides, lincosamides and streptogramins, and aminoglycosides. In conclusion, we have documented the ongoing successful reduction in total consumption of antimicrobials associated with a decrease in the incidence of HA-MRSA and the prevalence of MRSA over a 9-year period.


UnMICST: Deep learning with real augmentation for robust segmentation of highly multiplexed images of human tissues.
Upcoming technologies enable routine collection of highly multiplexed (20-60 channel), subcellular resolution images of mammalian tissues for research and diagnosis. Extracting single cell data from such images requires accurate image segmentation, a challenging problem commonly tackled with deep learning. In this paper, we report two findings that substantially improve image segmentation of tissues using a range of machine learning architectures. First, we unexpectedly find that the inclusion of intentionally defocused and saturated images in training data substantially improves subsequent image segmentation. Such real augmentation outperforms computational augmentation (Gaussian blurring). In addition, we find that it is practical to image the nuclear envelope in multiple tissues using an antibody cocktail thereby better identifying nuclear outlines and improving segmentation. The two approaches cumulatively and substantially improve segmentation on a wide range of tissue types. We speculate that the use of real augmentations will have applications in image processing outside of microscopy.


[Suggestions for improving the use of halo fixation with a metal construction piece].
An easier application of the halo fixation is obtained when the elbow linking the construction with the head ring is replaced by a double elbow possessing a lateral side length of 3 cm. This allows a better execution of X-ray examination in the lateral ray path.


Reliability of eccentric isokinetic knee flexion and extension measurements.
This study assessed the test-retest reliability of knee isokinetic eccentric muscle performance in subjects with and without a history of tibio-femoral pathology. Nineteen adults were tested at 60 degrees/sec and 180 degrees/sec on three occasions using a standardized protocol that incorporates a same-session learning phase. Results revealed moderate to excellent reliability for average peak torque test-retest ICC (2,1) = .58 to .96, total work ICC = .63 to .93, and power ICC = .67 to .93. Joint angle at peak torque was unreliable (ICC = .01 to .69) for both muscle groups at both angular velocities. Knee flexion reliability was higher than extension reliability at both 60 degrees/sec and 180 degrees/sec. Subjects with tibio-femoral pathologies had ICC values lower than the healthy subjects. Reliable eccentric isokinetic measurements can be obtained for average peak torque, total work, and power. Clinicians should not assume the same degree of reliability in testing patients as in testing healthy subjects.


Gestational hypertension plasma and human umbilical vein endothelial cells: an in vitro study.
The action of plasma from women affected by gestational hypertension (GH) on nitric oxide synthase (NOS) activity in cultured human umbilical vein endothelial cells (HUVECs) was evaluated in the present study, together with the effect on cytosolic calcium, on Na+, K+-ATPase activity and on membrane fluidity. At 80% confluence, cultured HUVECs were incubated for 3 h at 37 degreesC with fresh culture medium (control samples) or with 20% (v/v) plasma (from five healthy non-pregnant women, five healthy pregnant women and five pregnant women affected by GH). After incubation with GH plasma, we observed a significant reduction in NOS activity, intracellular calcium concentrations and Na+, K+-ATPase activity. The present work gives further support to the hypothesis that a circulating factor in gestational hypertension, possibly produced by the fetoplacental unit, causes dysfunction of the vascular endothelial cells and NO reduction, resulting in a loss of vascular refractoriness to vasoactive agents.


Calculating nectar production rates: residual nectar and optimal foraging.
Bumblebees, when foraging for nectar in flowers of Aconitum columbianum, do not consistently drain them of reward. The amount of residual nectar varies among sites, times and species of bee. At times, residual nectar can be a significant percentage of total 24 h production strongly suggesting that, if nectar secretion rates are to be studied, flowers must have their standing crop of nectar drained by hand; assuming that a recently visited blossom is empty can lead to erroneous nectar production values. The fact that residual nectar exists is consistent with predictions of optimal foraging theory but more detailed work is necessary before it can be concluded that the volumes left behind in A. columbianum flowers are optimal.


Composition of methane-oxidizing bacterial communities as a function of nutrient loading in the Florida everglades.
Agricultural runoff of phosphorus (P) in the northern Florida Everglades has resulted in several ecosystem level changes, including shifts in the microbial ecology of carbon cycling, with significantly higher methane being produced in the nutrient-enriched soils. Little is, however, known of the structure and activities of methane-oxidizing bacteria (MOB) in these environments. To address this, 0 to 10 cm plant-associated soil cores were collected from nutrient-impacted (F1), transition (F4), and unimpacted (U3) areas, sectioned in 2-cm increments, and methane oxidation rates were measured. F1 soils consumed approximately two-fold higher methane than U3 soils; additionally, most probable numbers of methanotrophs were 4-log higher in F1 than U3 soils. Metabolically active MOB containing pmoA sequences were characterized by stable-isotope probing using 10 % (v/v) (13)CH(4). pmoA sequences, encoding the alpha subunit of methane monooxygenase and related to type I methanotrophs, were identified from both impacted and unimpacted soils. Additionally, impacted soils also harbored type II methanotrophs, which have been shown to exhibit preferences for high methane concentrations. Additionally, across all soils, novel pmoA-type sequences were also detected, indicating presence of MOB specific to the Everglades. Multivariate statistical analyses confirmed that eutrophic soils consisted of metabolically distinct MOB community that is likely driven by nutrient enrichment. This study enhances our understanding on the biological fate of methane being produced in productive wetland soils of the Florida Everglades and how nutrient-enrichment affects the composition of methanotroph bacterial communities.


Auxarthron alboluteum related to non-dermatophytic toenail infection in Kurdistan region, Iraq: A case report.
We report a rare case of non-dermatophytic onychomycosis of the big toenail caused by Auxarthron alboluteum in a 63-years old Iraqi female with a history of diabetes. The big toenail showed distal subungual onychomycosis with extensive yellow-white discoloration. Identification of the causative agent was confirmed by morphological and microscopical characteristics in culture and analysis of ITS-rDNA region. To the best of our knowledge, the isolated Auxarthron alboluteum reported here is a new etiologic species of nail infection in Iraq and this is the first case of its kind to be reported in the world.


Postpartum angiopathy and other cerebral vasoconstriction syndromes.
The phenomenon of reversible cerebral arterial segmental vasoconstriction has been associated with several conditions including pregnancy and puerperium ("postpartum angiopathy"), thunderclap headache, and use of vasoconstrictive medications. Patients with cerebral vasoconstriction typically present with sudden, severe, and recurrent ("thunderclap") headaches and can develop strokes. Cerebral vasoconstriction syndromes are under- recognized, are poorly characterized, and are frequently misdiagnosed as primary cerebral vasculitis. This article presents an illustrative case report and reviews the historical aspects, clinical and imaging characteristics, etiology, differential diagnosis, management, and prognosis of cerebral vasoconstriction syndromes.


Technical validation of a new microfluidic device for enrichment of CTCs from large volumes of blood by using buffy coats to mimic diagnostic leukapheresis products.
Diagnostic leukapheresis (DLA) enables to sample larger blood volumes and increases the detection of circulating tumor cells (CTC) significantly. Nevertheless, the high excess of white blood cells (WBC) of DLA products remains a major challenge for further downstream CTC enrichment and detection. To address this problem, we tested the performance of two label-free CTC technologies for processing DLA products. For the testing purposes, we established ficollized buffy coats (BC) with a WBC composition similar to patient-derived DLA products. The mimicking-DLA samples (with up to 400 × 106 WBCs) were spiked with three different tumor cell lines and processed with two versions of a spiral microfluidic chip for label-free CTC enrichment: the commercially available ClearCell FR1 biochip and a customized DLA biochip based on a similar enrichment principle, but designed for higher throughput of cells. While the samples processed with FR1 chip displayed with increasing cell load significantly higher WBC backgrounds and decreasing cell recovery, the recovery rates of the customized DLA chip were stable, even if challenged with up to 400 × 106 WBCs (corresponding to around 120 mL peripheral blood or 10% of a DLA product). These results indicate that the further up-scalable DLA biochip has potential to process complete DLA products from 2.5 L of peripheral blood in an affordable way to enable high-volume CTC-based liquid biopsies.


Molecular species of mitochondrial phosphatidylcholine in rat liver and lung.
The acyl species of mitochondrial phosphatidylcholine from rat liver and lung were analysed by HPLC separation of the 1,2-diacyl-3-naphthylurethane derivatives. Comparison of phosphatidylcholine species patterns in microsomal, mitochondrial and submitochondrial fractions revealed only minor differences, whereas mitochondria from liver and lung differed markedly in the molecular composition of their respective phosphatidylcholine species.


Inhibitory Neuron Transplantation into Adult Visual Cortex Creates a New Critical Period that Rescues Impaired Vision.
The maturation of inhibitory circuits in juvenile visual cortex triggers a critical period in the development of the visual system. Although several manipulations of inhibition can alter the timing of the critical period, none have demonstrated the creation of a new critical period in adulthood. We developed a transplantation method to reactivate critical period plasticity in the adult visual cortex. Transplanted embryonic inhibitory neurons from the medial ganglionic eminence reinstate ocular dominance plasticity in adult recipients. Transplanted inhibitory cells develop cell-type-appropriate molecular characteristics and visually evoked responses. In adult mice impaired by deprivation during the juvenile critical period, transplantation also recovers both visual cortical responses and performance on a behavioral test of visual acuity. Plasticity and recovery are induced when the critical period would have occurred in the donor animal. These results reveal that the focal reactivation of visual cortical plasticity using inhibitory cell transplantation creates a new critical period that restores visual perception after childhood deprivation.


Management of juvenile and aneurysmal bone cysts: a systematic literature review with meta-analysis.
Numerous approaches to the management of juvenile and aneurysmal bone cysts (ABC) are described in the specialist literature together with discussion of the associated healing and recurrence rates. Since there is currently no evidence-based treatment standard for these conditions, the aim of this systematic literature review with meta-analysis was to examine the different management approaches, evaluate the corresponding clinical outcomes and, as appropriate, to formulate a valid treatment recommendation. A systematic search on OVID Medline® based on a pre-existing search strategy returned 1333 publications. Having defined inclusion and exclusion criteria and analysis of the relevant full texts, 167 publications were included in the descriptive analysis and 163 in the meta-analysis. For this purpose, different subgroups were created, based on the type of cyst and the therapeutic procedure. Those subgroups were then analysed in relation to their healing rates, the number of recurrences and complication rates. For aneurysmal bone cysts, both surgical removal and Doxycycline injection lead to excellent outcomes (98% healing) and low recurrence rates (6% and 11% resp.). Curettage (91% healing), including its combination with autologous cancellous bone graft (96% healing), showed very good healing rates but higher recurrence rates (22% and 15%, resp.), which were however improved by preoperative selective arterial embolization. A critical view must be taken of radiotherapy (90% healing) and the injection of alcohol (92% healing) because of their high complication rates (0.43/cyst and 0.42/cyst, resp.). In the management of juvenile bone cysts, surgical interventions like curettage and cancellous bone graft (87% healing) are far superior to non-surgical approaches (51% healing), furthermore, the application of autologous cancellous bone graft reduced the recurrence rate (3% recurrence) compared to curettage alone (20% recurrence). In subgroup analysis, treatment by ESIN was found to produce excellent outcomes (100% healing), though the patient collectives were small. Surgical procedures to treat aneurysmal bone cysts appear to be the method of choice whereby Doxycycline injection may be an alternative. A surgical approach should be preferred in the treatment of juvenile bone cysts.


Effect of light qualities on volatiles metabolism in maize (Zea mays L.) sprouts.
Maize sprouts are currently studied as one of novel nutritional sprout foods with special flavor. This study focused on the influences of light qualities on volatiles accumulation in maize sprouts by integrating transcriptomic and metabolic works. Fatty acid derivatives, including nonadecane and n-hexadecanoic acid were highly existed in maize sprouts. Besides, aldehydes and apocarotenoids were accumulated in light qualities whereas unsaturated fatty acids and sesquiterpenoids were declined by light qualities. The enhancements on fatty acid and phenylpropanoids/benzenoids derivatives of blue light quality were stronger than that of red light quality. In addition, there were nuances between blue and white light qualities, hence blue light quality was supposed to be an alternative energy-saving choice for cultivating maize sprouts. A MYB transcription factor was upregulated in light qualities and might play negative roles on linolenic acid degradation. C2H2 probably involved in the discrepant accumulation of terpenoids in maize sprouts treated by blue and red light qualities. The specific MYBs and bHLHs were correlated with terpenoid biosynthesis while a PL1 gene served as a potential regulator on phenylalanine biosynthesis flux. These findings provided new tactics for volatiles accumulation in maize sprouts as well as new insight into the volatile regulatory mechanism.


Molecular analyses of the hemagglutinin genes of H5 influenza viruses: origin of a virulent turkey strain.
Comparative sequence analysis of the hemagglutinin (HA) genes of a highly virulent H5N8 virus isolated from turkeys in Ireland in 1983 and a virus of the same subtype detected simultaneously in healthy ducks showed only four amino acid differences between these strains. Partial sequencing of six of the other genes and antigenic similarity of the neuraminidases established the overall genetic similarity of these two viruses. Comparison of the complete sequence of two H5 gene sequences and partial sequences of other virulent and avirulent H5 viruses provides evidence for at least two different lineages of H5 influenza virus in the world, one in Europe and the other in North America, with virulent and avirulent members in each group. In vivo studies in domestic ducks showed that all of the H5 viruses that are virulent in chickens and turkeys replicate in the internal organs of ducks but did not produce any disease signs. Additionally, both viruses isolated from turkeys and ducks in Ireland were detected in the blood. These studies provide the first conclusive evidence for the possibility that fully virulent influenza viruses in domestic poultry can arise directly from viruses in wild aquatic birds. Studies on the cleavability of the HA of virulent and avirulent H5 viruses showed that the principles established for H7 viruses (F. X. Bosch, M. Orlich, H. D. Klenk, and R. Rott, 1979, Virology 95, 197-207; F. X. Bosch, W. Garten, H. D. Klenk, and R. Rott, 1981, Virology 113, 725-735) also apply to the H5 subtype. These are (1) only the HAs of virulent influenza viruses were cleaved in tissue culture in the absence of trypsin and (2) virulent H5 influenza viruses contain a series of basic amino acids at the cleavage site of the HA, whereas avirulent strains contain only a single arginine with the exception of the avirulent Chicken/Pennsylvania virus. Thus, a series of basic amino acids at the cleavage site probably forms a recognition site for the enzyme(s) responsible for cleavage.


Antioxidant properties of coenzyme Q10-pretreated mouse pre-antral follicles derived from vitrified ovaries.
This study evaluated the antioxidant status of pre-antral follicles derived from vitrified ovaries pretreated with coenzyme Q10 (CoQ10). Mouse pre-antral follicles derived from fresh and vitrified warmed ovarian tissue were cultured with or without CoQ10 (50 μmol/L). Follicular growth, total antioxidant capacity (TAC), malondialdehyde (MDA) level, and superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activity during cultivation were assessed. The growth rate of the fresh pre-antral follicles was higher compared with the vitrified groups, especially in the CoQ10-treated than non-treated groups. MDA increased while TAC decreased at 96 h of the cultivation period. TAC was higher while MDA was lower in the fresh pre-antral follicles than in the vitrified groups. These rates were higher in the CoQ10-treated than non-treated groups. The vitrified and fresh CoQ10-pretreated groups had significantly higher SOD, GPX, and CAT activity compared with the CoQ10 non-treated groups. CoQ10-supplemented maturation medium can increase antioxidant enzyme activity and decrease lipid peroxidation in cultured pre-antral follicles derived from fresh and vitrified mouse ovaries.


Further evidence for multiple tachykinin receptors.
Rank order potency data for substance P (SP), physalaemin and eledoisin have been determined in a variety of assays in vitro. On the guinea-pig field stimulated vas deferens, physalaemin was approximately eight and five times more potent than eledoisin and SP respectively whereas in the rat field-stimulated vas deferens, eledoisin was approximately five times more potent than either physalaemin or SP. It would appear that the guinea-pig preparation has a preponderance of 'P'-receptor subtypes, whereas the rat preparation contains mainly 'E'-receptor subtypes. We have attempted to validate the hypothesis that there are multiple tachykinin receptors. Experiments have been performed with the guinea-pig urinary bladder in vitro, using phenoxybenzamine (20 microM, 30 min) to alkylate receptor sites and using excess eledoisin (0.2-0.4 microM, 30 min) to protect receptors selectively against the effects of this agent. Our results showed that after pretreatment with phenoxybenzamine, the responses to eledoisin were significantly attenuated. Moreover, in the presence of excess eledoisin it was found that phenoxybenzamine was unable to produce any significant reduction of the subsequent responses. This difference between the responses to eledoisin and to other agonists suggests the existence of at least two different receptor subtypes for the tachykinins.


Structure-Activity Relationship Probing of the Natural Marine Antifoulant Barettin.
The sponge derived 2,5-diketopiperazine metabolite barettin is a potent antifouling compound effective against the settlement and metamorphosis of barnacles. Simplified derivatives of barettin have previously been shown to display similar inhibitory properties. The synthetic derivative benzo[g]dipodazine has been reported to display significantly improved antifouling properties in comparison with the native barettin with inhibitory activities as low a 0.034 µM reported against barnacle cyprid settlement. In the current study we report the antifouling activity of 29 synthetic analogs designed and inspired by the potent antifouling effect seen for benzo[g]dipodazine. The library contains mainly not only dipodazine derivatives but also disubstituted diketopiperazines and compounds incorporating alternative heterocyclic cores such as hydantoin, creatinine, and rhodanine. Several of the prepared compounds inhibit the settlement of Amphibalanus improvisus cyprids at low micromolar concentrations, in parity with the natural barettin. While several highly active compounds were prepared by incorporating the benzo[g]indole as hydrophobic substituent, the remarkable antifouling effect reported for benzo[g]dipodazine was not observed when evaluated in our study.


Biochemical characterization of a recombinant Swainsona canescens calcium-dependent protein kinase (ScCPK1).
Calcium-dependent protein kinases (CPKs) constitute a unique family of kinases involved in many physiological responses in plants. Biochemical and kinetic properties of a recombinant Swainsona canescens calcium-dependent protein kinase (ScCPK1) were examined in this study. The optimum pH and temperature for activity were pH 7.5 and 37 °C, respectively. Substrate phosphorylation activity of ScCPK1 was calmodulin (CaM) independent. Yet CaM antagonists, W7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide] and calmidazolium inhibited the activity with IC(50) values of 750 nM and 350 μM, respectively. Both serine and threonine residues were found to be phosphorylated in autophosphorylated ScCPK1 and in histone III-S phosphorylated by ScCPK1. The [Ca(2)(+)] for half maximal activity (K(0.5)) was found to be 0.4 μM for ScCPK1 with histone III-S as substrate. Kinetic analysis showed that K(M) of ScCPK1 for histone III-S was 4.8 μM. These data suggest that ScCPK1 is a functional Ser/Thr kinase, regulated by calcium, and may have a role in Ca(2)(+)-mediated signaling in S. canescens.


Treatment of HBV Cirrhosis with Fuzheng Huayu Tablet () and Entecavir: Design of a Randomized, Double-Blind, Parallel and Multicenter Clinical Trial.
Antiviral therapy can lead to regression of fibrosis in chronic hepatitis B (CHB), but it has a limited effect on cirrhosis. Chinese medicines (CMs), particularly Fuzheng Huayu Tablet (, FZHY), have an antifibrotic effect in patients with CHB. To observe the safety and efficacy of adjunctive FZHY in patients with hepatitis B virus (HBV) cirrhosis, this study was designed as a randomized, placebo-controlled, double-blind, parallel assignment, multicenter trial at 20 centers in China. The total 700 naive patients will be enrolled with compensate cirrhosis due to HBV, and randomly assigned into 2 groups, receiving entecavir (0.5 mg, daily) and FZHY placebo (1.6 g, 3 times a day), or entecavir (0.5 mg, daily) and FZHY (1.6 g, 3 times a day), respectively. The primary endpoint was histological improvement at week 48. The secondary outcome is the decline values of liver fibrosis using the noninvasive methods from baseline to week 48 in each arm of the study. Adverse events such as stomach upset, headache, fatigue, dizziness, nausea will be strictly recorded. Through this study, we hope to generate a solid evidence for the therapeutic strategy of HBV cirrhosis with a combination of anti-viral such as ETV and anti-fibrotic herbal product such as FZHY. Protocol version: Version 1.3, Date: 2014.12.4. NCT02241590.


Single-Domain Antibodies for Intracellular Toxin Neutralization.
Ricin is a plant-derived toxin with a history as a biothreat agent. The toxin's enzymatic subunit, ricin toxin A chain (RTA), is a ribosome-inactivating protein that, when delivered into the cytoplasm of mammalian cells, arrests protein synthesis with extraordinary efficiency. Once within the cytoplasm, RTA is shielded from circulating toxin-neutralizing antibodies. Here, we describe methods we developed to neutralize RTA within the cytoplasm of Vero cells using DNA-based delivery of alpaca-derived single-domain antibodies (VHHs) targeting RTA's active site. We describe the design of the VHH expression vectors, assessment of transient expression of VHHs in Vero cells by enzyme-linked immunosorbent assay and western blotting, and cytotoxicity studies. While the protocols here are specific to ricin, they are easily modified for other toxins or even intracellular pathogens such as viruses.


Goal-directed hemodynamic management in patients undergoing primary debulking gynaecological surgery: A matched-controlled precision medicine study.
Usefulness of intraoperative goal-directed hemodynamic management (GDHM) for patients without comorbidities is debated. After clinical implementation of a pulse contour analysis-guided GDHM protocol, which foresees early vasopressor use for recruiting unstressed volume, we conducted a matched-controlled analysis to explore its impact on the amount of fluids intraoperatively administered to patients without comorbidities who underwent extended abdominal surgery for ovarian cancer. After 1:1 matching accounting for body mass index, oncologic disease severity and intraoperative blood losses, 22 patients treated according to this GDHM protocol were compared to a control group of 22 patients who had been managed according to the clinical decision of attending physicians, taken without advanced monitoring. Results are displayed as median[interquartile range]. All analyzed patients underwent radical hysterectomy, bilateral adnexectomy, bowel resection, peritonectomy and extended pelvic/periaortic lymphadenectomy; median length of surgery was 517[480-605] min in patients receiving GDHM and 507[480-600] min in control group. Intraoperatively, patients undergoing GDHM received less fluids (crystalloids 2950[2700-3300] vs. 5150[4700-6000] mL, p < 0.001; colloids 100[50-200] vs. 750[500-1000] mL, p < 0.001) and showed a trend to more frequent vasopressor administration (32 vs 9%, p = 0.13). Greater intraoperative diuresis (540[480-620] mL vs. 450[400-500] mL, p = 0.007), lower blood lactates at surgery end (1.5[1.1-2] vs. 4.1[3.3-5] mmol/L, p < 0.001), shorter time to bowel function recovery (1 [1, 2] vs. 4 [3-5] days, p < 0.001) and hospital discharge (7 [6-8] vs 12 [9-16] days, p < 0.0001) were detected in patients receiving GDHM. In high-tumor load gynaecological patients without comorbidities who receive radical and prolonged surgery, intraoperative use of this novel GDHM protocol helped limit fluids administration with safety.


Using Mobile Phones to Improve Vaccination Uptake in 21 Low- and Middle-Income Countries: Systematic Review.
The benefits of vaccination have been comprehensively proven; however, disparities in coverage persist because of poor health system management, limited resources, and parental knowledge and attitudes. Evidence suggests that health interventions that engage local parties in communication strategies improve vaccination uptake. As mobile technology is widely used to improve health communication, mobile health (mHealth) interventions might be used to increase coverage. The aim of this study was to conduct a systematic review of the available literature on the use of mHealth to improve vaccination in low- and middle-income countries with large numbers of unvaccinated children. In February 2017, MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, and Web of Science, as well as three health organization websites-Communication Initiative Network, TechNet-21, and PATH-were searched to identify mHealth intervention studies on vaccination uptake in 21 countries. Ten peer-reviewed studies and 11 studies from white or gray literature were included. Nine took place in India, three in Pakistan, two each in Malawi and Nigeria, and one each in Bangladesh, Zambia, Zimbabwe, and Kenya. Ten peer-reviewed studies and 7 white or gray studies demonstrated improved vaccination uptake after interventions, including appointment reminders, mobile phone apps, and prerecorded messages. Although the potential for mHealth interventions to improve vaccination coverage seems clear, the evidence for such interventions is not. The dearth of studies in countries facing the greatest barriers to immunization impedes the prospects for evidence-based policy and practice in these settings.


Pemphigus foliaceus and oral lichen planus in a patient with systemic lupus erythematosus and thymoma.
A 49-year-old woman with systemic lupus erythematosus, and a history of thymoma and chronic white plaques of the oral mucosa, developed a blistering eruption which was diagnosed as pemphigus foliaceus based on clinical, histological and direct immunofluorescence findings. However, the white plaques had both the clinical and histological features of lichen planus, as well as intercellular antibodies suggestive of pemphigus. Such conditions in combination have been documented previously, but this is believed to be the first report of the coexistence of all four in one individual. The common mechanism underlying these four conditions may well be an immunological disturbance.


Distribution characteristics of low molecular weight organic acids in seawater of the Changjiang Estuary and its adjacent East China Sea: Implications for regional environmental conditions.
In this study, components, concentrations, distribution characteristics and sources of low molecular weight organic acids (LMWOAs) in seawater of the Changjiang Estuary and its adjacent East China Sea were investigated in March 2015. Lactic, acetic and formic acids were identified with their concentration range of 0-16.7, 0-42.7 and 0-6.7 μmol·L-1, respectively. In the surface seawater, high concentrations of LMWOAs appeared in the sea area close to the estuary and along the coast. LMWOAs were important fractions of dissolved organic carbon and acetic acid was dominant component of LMWOAs. Riverine, terrestrial input, phytoplankton and sediment release were important sources for the LMWOAs, and human activities were considered as dominant sources for them in sampling period. The consistency of regions with high concentrations of LMWOAs, eutrophication, seasonal hypoxia and frequent red tide occurrence suggested LMWOAs as potential indicators for evaluating pollution status in coastal areas.


Relevance of Akt phosphorylation in cell transformation induced by Jaagsiekte sheep retrovirus.
Expression of the JSRV envelope (Env) is sufficient to transform immortalized rodent fibroblasts. A putative docking site for the PI3-K kinase (Y(590)-X-X-M(593)) in the cytoplasmic tail of the transmembrane domain of the JSRV Env is a major determinant of viral-induced cell transformation. Akt is constitutively phosphorylated in rodent fibroblasts transformed by the JSRV Env. However, recent data suggest that Y590 and M593 are not necessary for JSRV Env-induced transformation of the immortalized chicken fibroblasts cell line DF-1. In this study we found that JSRV-induced transformation of DF-1 cells is Akt-independent. In addition, a replication-competent avian vector expressing the JSRV Env (RCASBP(A)+JE) was also able to induce transformation of primary chicken embryo fibroblasts (CEF). Vectors expressing JSRV Env Y590 mutants were still able to induce CEF cells transformation but not as efficiently as the vectors expressing the wild-type Env. In CEF cells, as in DF-1 cells, only the expression of the wild-type Env induced constitutive phosphorylation of Akt. Thus, in chicken cells, the degree of transformation induced by the JSRV Env is maximum in the presence of Y590 and Akt phosphorylation. We addressed the significance of Akt phosphorylation in rat 208F cells transformed by the JSRV Env and showed that Akt is indeed activated and shows kinase activity. Inhibitors of the PI-3K/Akt pathway reproducibly decreased the transformation efficiency of the JSRV Env. In vivo, we found phosphorylated Akt only in nasal tumors induced by the enzootic nasal tumor virus (ENTV), a JSRV-related beta-retrovirus. No evidence of Akt phosphorylation was found in lung tumor sections of sheep affected by pulmonary adenocarcinoma. As a whole, these results suggest that the activation of the PI-3K/Akt pathway contributes to the process of JSRV-induced cell transformation but most likely is not the primary determinant both in vitro and in vivo.


Vasculitis Mimics and Other Related Conditions.
The approach to diagnosis of primary systemic vasculitis can be challenging, often requiring consideration of important secondary causes of vasculitis and non-inflammatory mimics. An atypical pattern of vascular involvement and/or atypical features of primary vasculitis (eg, cytopenia, lymphadenopathy) should prompt a more thorough investigation into other diseases. Herein, we review selected mimics organized by the size of blood vessels typically affected.


A prospective 6-month analysis of the naturalistic use of aripiprazole - factors predicting favourable outcome.
To evaluate the effectiveness of aripiprazole in clinical practice. Prospective follow-up of patients consecutively prescribed aripiprazole in an acute mental health unit. Retrospective analysis of outcome from casenotes. Data were available on 228 patients. Fifty-one per cent discontinued aripiprazole over 6-month follow-up. Continuation with treatment was more likely in out-patients [relative risk (RR) 1.50; 95% CI: 1.13-2.00], those never before considered for clozapine treatment (RR 1.61, 95% CI: 1.06-2.44) and older patients [RR 1.05, 95% CI: 1.01-1.09 (per 5-year increase)]. The main reason for early discontinuation was the occurrence of minor adverse effects. Aripiprazole is effective in practice. Outcome is likely to be improved by careful patient selection and by attending to adverse effects experienced early in treatment.


Individualized intravenous thrombolytic strategy for acute ischemic stroke with large vessel occlusion on the era of mechanical thrombectomy: cases report.
Intravenous thrombolysis for acute ischemic stroke within 4.5 h after the onset of symptoms has become a standard therapy that is recommended by many trials and clinical guidelines. As on the era of mechanical thrombectomy for acute ischemic stroke with large vessel occlusions, whether intravenous thrombolysis (IVT) is still necessary, and how to choose the optimal dose are still controversy. Here, we reported two cases of acute ischemic stroke with large vessel occlusions that both achieved complete recanalization after IVT. Then, IVT was terminated in advance, and dynamic surveillance by DSA was performed to achieve individual treatment. However, both of the cases presented with hemorrhagic transformation. We analyzed the probable reasons and put forward thoughts from ourselves.


Hydrogen peroxide enhances iron-induced injury in isolated heart and ventricular cardiomyocyte in rats.
To explore the cardiac effects of iron with or without hydrogen peroxide, the isolated perfused rat heart and enzymatically isolated ventricular cardiomyocyte were used. It was shown that treatment with cell-permeable iron (Fe-HQ) for 10 min reduced the contractile amplitude and velocity and end diastolic cell length in the cardiomyocyte and increased the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and malondialdehyde (MDA) in the myocardium. The left ventricular developed pressure (LVDP), +/-dP/dtmax, and heart rate and coronary flow are showed a biphasic phase, an increase at first followed by a decline. Treatment with hydrogen peroxide for 10 min following Fe-HQ augmented the effect of iron with an increase in coronary LDH and CK release and myocardial MDA content, and decrease in LVDP, +/-dP/dtmax and heart rate. Perfusion of reduced glutathione with hydrogen peroxide counteracted these effects of Fe-HQ and hydrogen peroxide while dimethyl sulfoxide had no effect on the injury induced by Fe-HQ and hydrogen peroxide in the isolated rat heart. This suggests that augmentation of myocardial injury as a result of an increase in intracellular iron by hydrogen peroxide might involve the dysfunction of sulfydryl group containing proteins but not the hydroxyl radicals.


ABCB6 is dispensable for erythropoiesis and specifies the new blood group system Langereis.
The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis, but it is also suspected to contribute to anticancer drug resistance, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the genetic basis of the Lan blood group antigen expressed on red blood cells but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and we established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(-) blood type identified 10 different ABCB6 null mutations. This is the first report of deficient alleles of this human ABC transporter gene. Of note, Lan(-) (ABCB6(-/-)) individuals do not suffer any clinical consequences, although their deficiency in ABCB6 may place them at risk when determining drug dosage.


Structural analysis of a pectic polysaccharide from boat-fruited sterculia seeds.
The chemical structure of a water-soluble pectic polysaccharide (sterculia APS) isolated from boat-fruited sterculia seeds (Semen Sterculiae Lychnophorae) was elucidated using partial acid hydrolysis, methylation analysis and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. The results of partial acid hydrolysis revealed that sterculia APS contained galacturonic acids and rhamnose units in the backbone, and arabinose, galactose and xylose residues in the branched chains. Combined the methylation analysis results with NMR spectroscopy, a possible structure of APS was proposed as follow: the backbone consisted of the homogalacturonan (HG) named "smooth" regions by linear linkage of 1,4-α-D-GalpA, and the rhamnogalacturonan-I (RG-I) called "hairy" ones by the linkage of →4)-α-D-GalpA-(1→2)-α-L-Rhap-(1→partially substituted at O-4 of rhamnose units. The GalpA residues were partially methyl esterified and O-acetylated on C-2 and/or C-3. The side chains were mainly composed of araban and arabinogalactan by the linkages of T-, 1,3-, 1,5-L-Araf and T-, 1,4-, 1,6-, 1,3,6-, 1,3,4-D-Galp, attached to O-4 of the backbone rhamnose units.


Mutation spectra in fragile X syndrome induced by deletions of CGG*CCG repeats.
The fragile X syndrome results from expansions as well as deletions of the repeating CGG.CCG DNA sequence in the 5'-untranslated region of the FMR1 gene on the X chromosome. The relative frequency of disease cases promoted by these two types of mutations cannot be ascertained at present because the routine clinical assay monitors only expansions. At least 30 articles have been reviewed that document the involvement of deletions of part or all of the CGG.CCG repeats along with varying extents of DNA flanking regions as well as very small mutations including single base pair changes. Studies of deletion mutants of CGG.CCG tracts in Escherichia coli plasmids revealed a similar spectrum of mutagenic products. The triplet repeat tract in a non-B conformation is the mutagen, not the sequence per se in the right-handed B helix. Hence, molecular investigations in a simple model organism may generate useful initial information toward therapeutic strategies for this disease.


Comparative Study of Teachers in Regular Schools and Teachers in Specialized Schools in France, Working with Students with an Autism Spectrum Disorder: Stress, Social Support, Coping Strategies and Burnout.
The inclusion of students with Autism Spectrum Disorder (ASD) in schools is a source of stress for teachers. Specialized teachers have, in theory, received special training. To compare the experiences of teachers dealing with students with ASD in different classroom environments. A total of 245 teachers filled out four self-report questionnaires measuring perceived stress, social support, coping strategies, and burnout. Specialized teachers perceive their teaching as a challenge, can count on receiving help from colleagues, use more problem-focused coping strategies and social support seeking behavior, and are less emotionally exhausted than teachers in regular classes. This study highlights that teachers in specialized schools and classes have better adjustment, probably due to their training, experience, and tailored classroom conditions.


Nervous System Deletion of Mammalian INDY in Mice Mimics Dietary Restriction-Induced Memory Enhancement.
Reduced expression of the Indy (I'm Not Dead Yet) gene extends life span in Caenorhabditis elegans and Drosophila melanogaster and improves the metabolic heath of Mus musculus through inducing a physiological status akin to dietary restriction (DR). Although the function of Indy in aging and hepatic metabolism has been extensively studied, its role in the mouse nervous system remains unclear. Here, we explore the effect of mammalian Indy (mIndy, SLC13A5) gene deletion on murine cognitive function. Similar to what is seen in DR animals, systemic deletion of the mIndy gene (mIndy knockout [KO]) significantly improves memory performance and motor coordination of mice. Both DR and mIndy KO mice act normally in other behavioral tasks, including emotional, social, and food-seeking behaviors. Moreover, we find that tissue-specific deletion of mIndy in the nervous system is sufficient to improve memory performance, while liver-specific deletion has no effect on memory, and results in tests of motor coordination show no changes in either mutant. Mice with systemic or nervous system deletion of mIndy also exhibit increased hippocampal neurogenesis and dendritic spine formation in dentate granule cells; these changes are well-documented contributors to enhanced memory performance. Together, our studies demonstrate a critical role for brain-derived mIndy expression in the regulation of memory function in animals.


Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1).
Identification, synthesis and structure-activity relationship of small-molecule VIPR1 antagonists encompassing two chemical series are described.


Recombinant equine herpesvirus 1 (EHV-1) vaccine protects pigs against challenge with influenza A(H1N1)pmd09.
Swine influenza virus (SIV) is not only an important respiratory pathogen in pigs but also a threat to human health. The pandemic influenza A(H1N1)pdm09 virus likely originated in swine through reassortment between a North American triple reassortant and Eurasian avian-like SIV. The North American triple reassortant virus harbors genes from avian, human and swine influenza viruses. An effective vaccine may protect the pork industry from economic losses and curb the development of new virus variants that may threaten public health. In the present study, we evaluated the efficacy of a recombinant equine herpesvirus type 1 (EHV-1) vaccine (rH_H1) expressing the hemagglutinin H1 of A(H1N1)pdm09 in the natural host. Our data shows that the engineered rH_H1 vaccine induces influenza virus-specific antibody responses in pigs and is able to protect at least partially against challenge infection: no clinical signs of disease were detected and virus replication was reduced as evidenced by decreased nasal virus shedding and faster virus clearance. Taken together, our results indicate that recombinant EHV-1 encoding H1 of A(H1N1)pdm09 may be a promising alternative for protection of pigs against infection with A(H1N1)pdm09 or other influenza viruses.


A Worksite Weight Loss Program: An Innovative Way to Improve Obesity.
Obesity rates have continued to increase throughout the United States. Traditional healthcare settings have been unsuccessful at slowing down the epidemic. Finding innovative ways to improve obesity is critical. This article discusses a worksite weight loss program that utilized a group visit format to help participants lose weight, decrease waist circumferences, increase physical activity levels, and empower patients for change. A total of 18 participants completed the 6-week comprehensive weight loss program, which provided education and support on nutrition, physical activity, meal-planning, stress reduction, and goal setting. Participants in the worksite weight loss program showed improvements in several measured variables, including 100% of the participants achieving weight loss. In addition, 89% of the participants had a decrease in waist circumference, 53% improved their activity level, and 61% improved their level of readiness to change. Non-traditional settings, like worksites, as well as group-visit formats, can be successful in improving obesity rates in communities.


New Type of Aromatic π-Systems for Anion Recognition: Strong Anion-π and C-H⋅⋅⋅Anion Interactions Between Halides and Aromatic Ligands in Half-Sandwich Compounds.
Half-sandwich compounds of benzene, cyclopentadienyl, pentamethylcyclopentadienyl, and indenyl were studied as a new type of aromatic π-systems for interactions with halide anions. Although uncoordinated benzene forms only C-H⋅⋅⋅anion interactions, and hexafluorobenzene forms only anion-π interactions, aromatic ligands in half-sandwich compounds can form both types of interactions, because their entire electrostatic potential surface is positive. These aromatic ligands can form stronger anion-π interactions than organic aromatic molecules, as a consequence of more pronounced dispersion and induction energy components. Moreover, C-H⋅⋅⋅anion interactions of aromatic ligands are stronger than anion-π interactions, and significantly stronger than C-H⋅⋅⋅anion interactions of benzene. Our study shows that transition-metal coordination can make aromatic moieties suitable for strong interactions with anions, and gives insight into the design of new anion receptors.


Strategies for establishing organ transplant programs in developing countries: the Latin America and Caribbean experience.
The Latin America and Caribbean region is composed of 39 countries. It is remarkable the progress of transplantation in the region in despite of the low economic resources when compared to other regions. The criteria for brain death are well established and culturally accepted. The consent for retrieval is based on required family consent in most countries. The regulations for living donors are also well established, with restrictions to unrelated donors and prohibition of any kind of commerce. The access to transplant is limited by the model of public financing by each country, and those with public universal coverage have no financial restrictions to cover the costs for any citizen; in countries with restricted coverage, the access is restricted to the employment status. There is a progressive increment in the annual number of solid organ transplants in Latin America, reaching near 10,000 in 2004, accomplished by adequate legislation that is also concerned with the prohibition of organ commerce.


Use of Fillers in Rhinoplasty.
Surgical rhinoplasty is the one of the most common cosmetic procedures in Asians. But there are limitations, such as down time, high cost, and a steep learning curve. Most complications are implant related. A safer and less invasive procedure is rhinoplasty using fillers. Good knowledge of the nasal anatomy is essential for rhinoplasty using fillers. Knowledge of nerves, blood supply, and injection plane allows avoiding complications. There are several planes in the nose. The deep fatty layer is recommended for injection, because it is wide and loose and there are less important neurovascular structures. Botulinum toxin also can be used for noninvasive rhinoplasty.


SRSF1 regulates exosome microRNA enrichment in human cancer cells.
Exosomes are extracellular vesicles containing a variety of biological molecules including microRNAs (miRNAs). We have recently demonstrated that certain miRNA species are selectively and highly enriched in pancreatic cancer exosomes with miR-1246 being the most abundant. Exosome miRNAs have been shown to mediate intercellular communication in the tumor microenvironment and promote cancer progression. Therefore, understanding how exosomes selectively enrich specific miRNAs to initiate exosome miRNA signaling in cancer cells is critical to advancing cancer exosome biology. The aim of this study was to identify RNA binding proteins responsible for selective enrichment of exosome miRNAs in cancer cells. A biotin-labeled miR-1246 probe was used to capture RNA binding proteins (RBPs) from PANC-1 cells. Among the RBPs identified through proteomic analysis, SRSF1, EIF3B and TIA1 were highly associated with the miR-1246 probe. RNA immunoprecipitation (RIP) and electrophoretic mobility shift assay (EMSA) confirmed the binding of SRSF1 to miR-1246. Lentivirus shRNA knockdown of SRSF1 in pancreatic cancer cells selectively reduced exosome miRNA enrichment whereas GFP-SRSF1 overexpression enhanced the enrichment as analyzed by next generation small RNA sequencing and qRT-PCR. miRNA sequence motif analysis identified a common motif shared by 36/45 of SRSF1-associated exosome miRNAs. EMSA confirmed that shared motif decoys inhibit the binding of SRSF1 to the miR-1246 sequence. We conclude that SRSF1 mediates selective exosome miRNA enrichment in pancreatic cancer cells by binding to a commonly shared miRNA sequence motif. Video Abstract.


Congenital anomalies of the kidney and urinary tract (CAKUT): a current review of cell signaling processes in ureteral development.
The objective of this review is to present a concise summary of the genetic signaling processes involved in abnormal mouse Wolffian development and their correlation to those abnormalities affecting ureteral development in children. We performed an extensive review of the current literature pertaining to mouse Wolffian duct development and combined these findings with our own data. This article reviews embryological findings in mice with ureteral abnormalities and draws connections between the mouse anomaly and what is seen in children. A review of the current literature has led to the identification of a number of genes which may prove to be important in understanding the causes of these anomalies.


L-carnitine treatment in the hyperlipidemic rabbit.
A study was designed to examine the hypolipidemic effect of L-carnitine treatment (4 weeks, 170 mg/kg/d) in rabbits fed a high fat diet (5% corn oil/0.5% cholesterol, w/w). Eight weeks of exposure to the high fat diet significantly increased plasma total cholesterol and triglycerides. VLDL associated triglycerides, cholesterol, apo-B, and total protein were also significantly increased with the diet. There was no change in HDL-cholesterol levels. Plasma concentration of carnitine (free, acyl, and total) all increased significantly with the high fat diet. The content of free, short-chain, and total carnitine were decreased in the liver whereas the content of long-chain acylcarnitines was increased. The diet generated a significant steatosis within the livers of these animals. Four weeks of treatment of L-carnitine reduced the extent of the liver steatosis and significantly decreased plasma total cholesterol, triglycerides, VLDL associated triglycerides, cholesterol, and total protein. HDL-cholesterol levels were unaffected by the treatment. All plasma fractions of carnitine (free, acetyl, acyl, and total) were significantly increased above those levels seen after 8 weeks of the high fat diet alone. The content of liver carnitine and its esters was normalized following treatment. The high fat diet decreased liver HMG-CoA reductase activity and increased the activities of 7-alpha-hydroxylase and acylcholesterol acyltransferase (ACAT). L-Carnitine treatment blunted the magnitude of the diet induced increase in 7 alpha-hydroxylase activity, yet overall the activity still remained elevated relative to controls. ACAT activity increased (1.5 times) with the high fat diet and increased further (4.5 times) following carnitine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


The Impacts of COVID-19 on Mental Health and Training in US Professional Endurance Athletes.
We examined how professional athletes are affected by COVID-19. Our primary aim was to assess changes in mental health that occurred after COVID-19 restrictions, and our secondary aim was to assess changes in exercise volume and intensity. Cross-sectional study. United States. Strava professional endurance athletes. Participants completed a survey, and a subset of participants consented to have their activity data analyzed. The survey included questions on COVID-19 symptoms, exercise, and mental health, as measured by a modified Patient Health Questionnaire. Participants were asked about 2 periods in 2020: before COVID-19 (January 1-March 14) and during COVID-19 (March 15-August 25), and activity data from both periods were downloaded. Activity data consisted of Global Positioning System and self-reported uploads. One hundred thirty-one male and female Strava athletes were enrolled, and a subset of athletes (n = 114) consented to have their activity data analyzed. During COVID-19 restrictions, 22.2% of participants reported feeling down or depressed and 27.4% of participants reported feeling nervous or anxious at least half the days in a week compared with 3.8% and 4.6% before COVID-19 restrictions, respectively (P < 0.0001). Activity data revealed a significant increase (P < 0.0001) in exercise minutes per day during COVID-19 (mean = 103.00, SD = 42.1) compared with before COVID-19 restrictions (mean = 92.4, SD = 41.3), with no significant changes in intensity. Athletes reported significant increases in feeling down or depressed and nervous or anxious despite an increase in exercise duration during COVID-19. Future research should assess how to support athletes with mental health resources.


Retracted: Dynamic Performance Analysis of STEP System in Internet of Vehicles Based on Queuing Theory.
[This retracts the article DOI: 10.1155/2022/8322029.].


In vitro differentiation of embryonic stem cells into the pancreatic lineage.
Embryonic stem (ES) cells represent a potential source of transplantable cells for the treatment of diabetes because of their almost unlimited proliferation capacity and the potential to differentiate into insulin-producing cells. The differentiation conditions significantly affect the development of pancreatic cells from ES cells in vitro. Here, we describe an efficient strategy for the in vitro generation of insulin-producing cells. The protocol includes the spontaneous generation of multilineage progenitor cells and their differentiation induction by growth and extracellular matrix factors into C-peptide/insulin-positive islet-like clusters. The differentiated cells release insulin in response to high glucose concentrations. No specific selection for nestin-positive cells is performed at any time of ES cell differentiation.


Validation of the 6-Item Cognitive Impairment Test and the 4AT test for combined delirium and dementia screening in older Emergency Department attendees.
screening for cognitive impairment in Emergency Department (ED) requires short, reliable tools. to validate the 4AT and 6-Item Cognitive Impairment Test (6-CIT) for ED dementia and delirium screening. diagnostic accuracy study. attendees aged ≥70 years in a tertiary care hospital's ED. trained researchers assessed participants using the Standardised Mini Mental State Examination, Delirium Rating Scale-Revised 98 and Informant Questionnaire on Cognitive Decline in the Elderly, informing ultimate expert diagnosis using Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for dementia and delirium (reference standards). Another researcher blindly screened each participant, within 3 h, using index tests 4AT and 6-CIT. of 419 participants (median age 77 years), 15.2% had delirium and 21.5% had dementia. For delirium detection, 4AT had positive predictive value (PPV) 0.68 (95% confidence intervals: 0.58-0.79) and negative predictive value (NPV) 0.99 (0.97-1.00). At a pre-specified 9/10 cut-off (9 is normal), 6-CIT had PPV 0.35 (0.27-0.44) and NPV 0.98 (0.95-0.99). Importantly, 52% of participants had no family present. A novel algorithm for scoring 4AT item 4 where collateral history is unavailable (score 4 if items 2-3 score ≥1; score 0 if items 1-3 score is 0) proved reliable; PPV 0.65 (0.54-0.76) and NPV 0.99 (0.97-1.00). For dementia detection, 4AT had PPV 0.39 (0.32-0.46) and NPV 0.94 (0.89-0.96); 6-CIT had PPV 0.46 (0.37-0.55) and NPV 0.94 (0.90-0.97). 6-CIT and 4AT accurately exclude delirium and dementia in older ED attendees. 6-CIT does not require collateral history but has lower PPV for delirium.


Colorectal carcinoma in the elderly: a geriatric and surgical practice compared.
Two hundred and eighty-eight patients with colorectal cancer over the age of 65 years admitted to either the geriatric unit or a surgical unit have been compared. Significant differences in presentation and outcome were found and are discussed. Despite adverse factors, acceptable results were obtained for surgical treatment in the geriatric group.


Regeneration of the ureter and the renal pelvis in dogs from transversely transected and anastomosed strips of the ureteral wall. Influence of long administration of azathioprine and prednisone on the newly formed wall. I. Experimental.
Regeneration of the ureter and renal pelvis from a transected and anastomosed strip of the ureteral wall was examined in 20 dogs. The latter were divided into two groups: group A, dogs operated without receiving any drug, and group B, dogs which received 1.5 mg prednisone and 1.5 azathioprine/kg body weight/day before the operation and throughout the postoperative period. Provided the ureteral splint was maintained for at least 28 days, good results were obtained in both groups. Long-term administration of the drugs thus had no adverse effects on the regeneration. Microscopic examination of the newly formed wall, showed more numerous and better arranged muscular fibers and less connective tissues in group B.


Direct imaging of transvenous radiofrequency cardiac ablation using a steerable fiberoptic infrared endoscope.
Direct imaging through blood has been achieved in vivo using fiberoptics and infrared wavelength technology. The purpose of this study was to determine the feasibility of using a percutaneous, steerable, fiberoptic infrared endoscope to identify and characterize the electrode-tissue interface during transvenous cardiac ablation. Infrared endoscopy was performed during 24 catheter ablation attempts in 10 mongrel dogs. Infrared imaging was performed through a transparent dome located at the tip of a 7Fr steerable endoscope using an imaging wavelength of 1,620 nm. Radiofrequency ablation was performed using a 4-mm-tip electrode catheter. Attempts were made to identify the electrode-endocardial interface at each ablation site and to characterize any signal changes during ablation. The electrode-tissue interface could be identified at 19 of the 24 ablation sites. Changes at the electrode-tissue interface were observed during ablation at 14 sites, which included a gradual increase in the tissue signal intensity at 12 sites. Small lucencies near the ablation electrode were observed at six sites. There was no interference during energy delivery. Endocardial features identified by endoscopy correlated with the postmortem appearance. Direct imaging of intracardiac structures and the electrode-tissue interface can be achieved through blood during transvenous catheter ablation with infrared endoscopy using a steerable, fiberoptic, infrared endoscopic catheter. Ablation lesion formation can be seen as a gradual increase in signal intensity. Fiberoptic infrared endoscopy appears to be a promising new tool for guiding catheter ablation.


Cancer risk of sulfonylureas in patients with type 2 diabetes mellitus: A systematic review.
Increasing evidence suggests that oral hypoglycemic agents used in type 2 diabetes mellitus (T2DM) may affect cancer risk. Sulfonylureas (SUs) are the most frequently used antidiabetic medications for T2DM. Whether using SUs has any effect on cancer has received considerable attention. The aim of this study was to assess the effects of SUs on cancer risk in T2DM patients. Published studies were identified in PubMed, EMBASE, and the Cochrane Register of Clinical Studies, and ClinicalTrials.gov was searched for additional information to identify randomized controlled trials (RCTs), cohort studies, and case-control studies. The abstracts and full text were screened, data collected, and the risk of bias assessed for each individual study. Seventy-seven studies (33 RCTs, 27 cohort studies, and 17 case-control studies) were analyzed. The RCTs did not report a difference in the risk of malignant tumor between SU-treated T2DM patients and controls (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.78-1.18); cohort studies showed that cancer risk was higher in patients using SUs than metformin (relative risk 1.60 [95%CI 1.37-1.87]; adjusted hazard ratio 1.13 [95%CI 1.06-1.19]), and case-control studies suggested a trend for increased cancer risk in those using SUs compared with non-SU users (adjusted OR 1.13; 95%CI 0.93-1.37). The available evidence clearly shows that SUs can significantly increase the risk of cancer compared with metformin. Although the evidence suggests the possibility that SU users may have a higher risk of cancer than those using alternative medications in addition to metformin, it remains inadequate to enable definitive conclusions to be drawn.


Preparation of colloidal polydopamine/Au hollow spheres for enhanced ultrasound contrast imaging and photothermal therapy.
Development of functional theranostic platform for systemic contrast-enhanced diagnostic imaging and therapy is of great necessity in nanomedicine. However, synthesizing the biocompatible theranostic agents with enhanced merits in imaging and therapy via a facile and green way is still highly challenged. Here, we report a novel theranostic agent based on colloidal polydopamine/Au (PDA/Au) hollow spheres, which are synthesized with combined use of PDA chemistry and sacrificial template techniques. Colloidal polystyrene (PS) spheres serve as the templates with coatings of a PDA shell and Au nanoparticles in sequence, which are subsequently removed with trichloromethane, giving rise to colloidal PDA/Au hollow spheres. Colloidal PDA/Au hollow spheres exhibit excellent contrast enhancement for ultrasound imaging, and can serve as the near-infrared (NIR) photoabsorbers for the effective photothermal ablation of 4 T1 breast cancer cells in vitro with minor cytotoxicity to living cells. This method suggests a novel avenue for theranostic treatment in oncology.


Relation between degree of weight loss after bariatric surgery and reduction in albuminuria and C-reactive protein.
Bariatric surgery achieves long-term weight loss in obese adults with amelioration of diabetes and hypertension. Improvement in albuminuria and high-sensitivity C-reactive protein (hs-CRP) has also been reported. We investigated, at a weight control center in a community hospital setting, the relation between degree of surgical weight loss and reduction in the cardiovascular risk markers, albuminuria and hs-CRP. We performed a retrospective study of 62 obese adults who had undergone Roux-en-Y gastric bypass surgery and had a median follow-up of 15 months. The baseline (preoperative) mean age was 46 years, 82% were women, 26 had a blood pressure of > or =140/90 mm Hg, and 25 had type 2 diabetes. During follow-up (postoperative), a decrease occurred in the body mass index (mean +/- standard deviation 49.2 +/- 8.7 kg/m(2) to 34.1 +/- 8.1 kg/m(2); P <.0001), excess body weight (mean +/- SD 76.1 +/- 23.6 kg to 34.9 +/- 21.7 kg; P <.0001), hemoglobin A1c (mean +/- SD 6.5% +/- 1.3% to 5.6% +/- 0.8%; P <.0001), systolic blood pressure (mean +/- SD 133.7 +/- 14.3 mm Hg to 112.9 +/- 14.6 mm Hg; P < .0001), urine albumin creatinine ratio (from a median of 8.0 mg/g [interquartile range 5.0-29.3] to a median of 6.0 mg/g [interquartile range 3.3-11.5]; P <.0001), and hs-CRP (mean +/- SD 11.2 +/- 9.8 mg/L to 4.7 +/- 5.9 mg/L; P <.0001). The study sample was divided into tertiles of the percentage of excess body weight loss; the mean percentage of excess body weight loss was -37.1% +/- 5.5% in the first tertile, -54.3% +/- 6.8% in the second tertile, and -75.8% +/- 10.9% in the third tertile. The median percentage of change in albuminuria was greatest (median -52.8%, interquartile range -79.1% to -17.5%) in the third tertile, intermediate (median -45.5%, interquartile range -72.4% to 0%) in the second tertile, and lowest (-42.6%, interquartile range -80.5% to 16.7%) in the first tertile (P = .953). The mean percentage of change in hs-CRP was greatest (-72.4% +/- 30.4%) in the third tertile, intermediate (-55.4% +/- 31.9%) in the second tertile, and lowest (-44.8% +/- 30.6%) in the first tertile (P = .037). The results of our study have shown that obese adults experience a reduction in albuminuria and hs-CRP after bariatric surgery, with a greater reduction in hs-CRP observed with more surgical weight loss.


Antilipid a monoclonal antibody HA-1A: immune complex clearance of endotoxin reduces TNF-alpha, IL-1 beta and IL-6 production.
HA-1A is a human monoclonal IgM antibody which recognizes the lipid A component of lipopolysaccharide (LPS). This antibody has reduced mortality in the septic shock syndrome resulting from Gram negative bacteria, in which many of the manifestations are considered to be due to cellular activation and secretion of cytokines, most notably TNF-alpha. However HA-1A does not directly neutralize LPS effectively in vitro, and studies reported to date have not defined its mechanism of action. Here we demonstrate that HA-1A, which in the presence of complement promotes immune adherence, may inhibit LPS action by facilitating its sequestration on red blood cells and clearance to an extent that cytokine production is reduced. Incubation of LPS at clinically significant (pg/ml) does with HA-1A at therapeutic levels (e.g. 10 micrograms/ml) and complement resulted in LPS association with erythrocyte CR1 receptors. This reduced the ability of the residual, free LPS by 50-70% to induce the secretion of TNF-alpha, IL-1 beta and IL-6 from normal blood mononuclear cells. This mechanism is likely to be operative in vivo, and could account for the protective effect of HA-1A, and its reduction of TNF-alpha production in vivo.


Is Usual Dietary Pattern Related to the Risk of Developing Breast Cancer?
Dietary patterns capture total diet providing a more comprehensive understanding of the effect of diet on chronic disease risk. Dietary patterns have been associated with several chronic diseases, including cardiovascular disease and selected cancers; however, the association with breast cancer remains unclear. The objective of this review was to examine critically the most recent literature on dietary patterns and breast cancer and report on current results, new developments, and future directions. Seven case-control and cohort studies from multiple countries have been published during the previous year (2011-2012). Many have analyzed a posteriori dietary patterns via factor and principal component analysis. Whereas results remain mixed, the majority of studies indicate healthier patterns decrease breast cancer risk, although patterns higher in meat and alcohol increase risk. Future studies that examine the associations between diet and tumor subtypes and collect dietary data at younger ages and, if possible, longitudinally would be beneficial.


Activity limitations before and after surgical carpal tunnel release among patients with and without diabetes.
To evaluate activity limitations before and after carpal tunnel release among patients with and without diabetes, to explore differences between genders and the influence of grip strength on activity limitations. Prospective case-control study. Thirty-three patients with diabetes and carpal tunnel syndrome (CTS) were age and gender matched with 30 patients without diabetes having idiopathic CTS. Activity limitations were assessed pre-operatively, 3 and 12 months after surgery, with the self-administered Evaluation of Daily Activities Questionnaire (EDAQ) containing 102 activity items in 11 dimensions and 3 additional male-activity-oriented dimensions including 22 items. For all dimensions the mean score was higher for patients with diabetes compared with patients without diabetes. This indicates a more pronounced activity limitation for patients with diabetes. However, no statistical differences between the two groups could be demonstrated. In general, females have significantly higher activity limitation scores than males. CTS creates a broad variety of activity limitations for affected patients. After carpal tunnel release a significant alleviation of these limitations occurs within the first 3 months. Activity limitations seem not to be related to diabetes, but were more pronounced in women than in men, probably due to reduced grip strength.


Exploring the absolute yield curve of secondary electrons using machine learning methods.
Knowledge of absolute secondary electron yield (δ) is important for various applications of electron emission materials. Besides, it is also crucial to know the dependence of δ on primary electron energy Ep and material properties like atomic number Z. The available experimental database of δ reveals a large discrepancy among the measurement data, while the oversimplified semi-empirical theories of secondary electron emission can only present the general shape of the yield curve but not the absolute yield value. This limits not only the validation of a Monte Carlo model for theoretical simulations but also presents large uncertainties in the applications of different materials for various purposes. In applications, it is highly desirable to have the knowledge of the absolute yield of a material. Therefore, it is highly desirable to establish the relationship of the absolute yield with material and electron energy based on the available experimental data. Recently, machine learning (ML) methods have been increasingly used for the prediction of material properties mainly based on the atomistic calculations with the first-principles theory. We propose here the application of ML models to a material property study, starting with experimental observations and unfolding the relationship of δ with basic material properties and primary electron energy. Our ML models are able to predict δ(Ep)-curve covering a wide energy range of 10 eV-30 keV for unknown elements within the uncertainty range of the experimental data and can suggest more reliable data among the scattered experimental data.


Visual field change in low-tension glaucoma over a five-year follow-up.
There is some evidence that the nature and progression of disease in low-tension glaucoma may be distinct from other open-angle glaucomas. The authors assessed visual field change by retrospective case review of all patients treated for low-tension glaucoma by the Glaucoma Service, Wills Eye Hospital, for at least 5 years. Sixty-two glaucomatous eyes of 36 patients were identified. All eyes were treated medically and 40 (65%) underwent at least one surgical procedure. Twenty-eight eyes (47%) had initial field loss confined to a single hemi-field and in the remainder both hemi-fields were involved. Thirty of 57 eyes (53%) showed progression at 3 years and 38 (62%) of 57 had progressed by 5 years. A dense scotoma extending from the nasal periphery toward fixation was the most common visual field defect. The rate of field change in this population is significantly greater than in a cohort of primary open-angle glaucoma patients also seen at Wills Eye Hospital, but who had elevated intraocular pressures. Patterns of field loss and rate of progression in this low-tension glaucoma population suggest that the natural history of low-tension glaucoma differs from high-tension open-angle glaucoma.


Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial.
Despite initial response to chemotherapy, at least 50% of ovarian cancer patients will relapse within 18 months. Progression-free survival is related to tumour infiltration with cytotoxic T lymphocytes (CTL). We recently demonstrated that CD8+ T cell responses to recall antigens improve following tumour response to chemotherapy. Vaccination designed to expand CTL, specific for tumour-associated antigens, may be a means of improving outcome. We are planning a clinical trial in advanced ovarian cancer patients undergoing chemotherapy using a combination of a Toll-like receptor 3 (TLR3) agonist and tumour-associated ascites-derived exosomes. Tumour-derived exosomes are a potential source of tumour antigens able to induce CD8+ T cell responses when loaded on mature dendritic cells (DC). DC maturation can be achieved with Toll-like receptor (TLR) agonists, such as the GMP-grade synthetic double stranded RNA, poly[I]:poly[C12U] (Ampligen) which is a TLR-3 agonist. Here, we describe the development of a method suitable for the preparation of GMP-grade exosomes from the ascites fluid of ovarian cancer patients, and the methods used for the molecular and immunological characterisation of these exosomes preceding their use in a clinical trial.


Carbon Dots with Blue-to-Near-Infrared Lasing for Colorful Speckle-Free Laser Imaging and Dynamical Holographic Display.
As a new solution-processable laser material, carbon dots (CDs) offer advantages of non-toxicity, low-cost, and high-stability, which are conducive to the sustainable development of miniaturized lasers. Full-color CDs (FC-CDs) with bright-blue, green, yellow, red, deep-red, and near-infrared (NIR) fluorescence are prepared. Their photoluminescence emission ranges from 431 to 714 nm. The FC-CDs show narrow full widths at half maximum in the range of 44-76 nm, with concurrent high radiative transition rates (KR ) of 0.54-1.74 × 108 s-1 ; their performance is comparable to that of organic laser dyes, indicating their good gain potential for lasers. Laser pumping of the FC-CDs gives laser outputs at 467.3, 533.5, 577.4, 616.3, 653.5, and 705.1 nm, spanning from blue to NIR region, and covering 140% of the NTSC color gamut. The FC-CDs show high Q-factors (2000-5500), appreciable gain coefficients (9-21.5 cm-1 ), and better stability (≈100%@4-7 h) than commercial laser dyes. These excellent properties make them suitable for high-quality, colorful, speckle-free laser imaging and dynamic holographic display. The findings will be helpful in promoting the practical applications and development of solution-processable CD-based lasers.