Physicochemical and biological properties of human and canine plasmins.
Three kinds of plasmin were found to be generated when plasminogen or [(125)I]plasminogen was incubated at 32 degrees C for longer than 20 min in urokinase and 50% glycerol. Each plasmin was then separated by G-200 or G-75 Sephadex filtration, and its physicochemical properties were determined. The molecular weights of the three plasmins as determined by G-200 Sephadex filtration were 125,000+/-5,000(SD), 63,000+/-2,000(SD), and 31,500+/-1,000(SD), and those by sodium dodecyl sulfate(SDS)-polyacrylamide electrophoresis were 130,000+/-5,000(SD), 64,000+/-3,000(SD), and 32,000+/-1,500(SD). It was also found that during the incubation of the smallest plasmin in SDS and beta-mercaptoethanol it was further split into two smaller pieces of about 16,000 mol wt and that polymer proteins of 95,000+/-2,000(SD) and 48,000+/-1,500(SD) mol wt were formed. Despite these differences in the molecular size of the three plasmins, the specific activity of each plasmin was closely similar and in case of human plasmins averaged 29+/-0.9(SD) CTA units/mg plasmin and in case of canine plasmins 8.5+/-0.54(SD) CTA units/mg plasmin. Then, using human plasmin of the smallest size (mol wt 31,500), the total plasma antiplasmin capacity was determined in 20 normal human plasma, which averaged 7.8+/-2(SD) CTA units of plasmin per milliliter plasma. Studies were next made of the affinity of human [(125)I]-plasmin of the smallest size with albumin, gamma globulin, alpha(2)-macroglobulin, alpha(1)-antitrypsin, fibrinogen, and fibrin. The results were 0%, 0%, 14.6+/-0.5(SD)%, 17.6+/-0.6(SD)%, 21+/-0.5(SD)%, and 20.5+/-0.6(SD)%, respectively, of [(125)I]plasmin available and were unaltered when the amount of [(125)I]plasmin was increased to twice and four times the original amount. Finally, the plasma disappearance half-life of canine [(125)I]plasmin of the smallest size was studied in five healthy dogs, which averaged 14.2+/-0.63(SD) h. These results support the concept that the combination between plasmin and plasmin inhibitors is reversible and indicate that fibrinogen and fibrin have greater affinities than alpha(2)-macroglobulin or alpha(1)-antitrypsin.


Characteristics of CT Perfusion Parameters of Focal Pancreatic Lesions and Data Comparison of Different Algorithms.
Objective To characterize the CT perfusion parameters of focal pancreatic lesions including pancreatic cancers (PACs) and pancreatic neuroendocrine tumors (pNETs),estimate the confirmity and fungibility of parameters obtained from Deconvolution and Maximum slope+Patlak.Methods From December 2015 to November 2016,22 patients with PACs and 22 patients with pNETs(37 lesions confirmed by surgery and biopsy)underwent preoperative whole-pancreas CT perfusion in our center. The volume perfusion CT of the entire pancreas was performed at 80 kV and 100 mA,using 28 consecutive volume measurements and intravenous injection of 45 ml of iodinated contrast and saline at a flow rate of 5 ml/s. One experienced radiologists measured and recorded the CT perfusion parameters on Siemens post-processing workstation using two mathematical methods:Maximum slope+Patlak analysis versus Deconvolution method.ResultsWilcoxon matched-pairs test revealed significant difference between both pairs of the perfusion measurements by the two methods,PACs(BFM vs. BFD,Z=-3.263,P=0.001;BVD vs. BVP,Z=-3.978,P=0.000); pNETs(BFM vs. BFD,Z=-5.212,P=0.000;BVD vs. BVP,Z=-2.633,P=0.008). Spearman's correlation coefficient showed both pairs of perfusion measurements significantly correlated with each other in PACs (BFM vs. BFD,r=0.845,P=0.000;BVD vs. BVP,r=0.964,P=0.000) and pNETs(BFM vs. BFD,r=0.759,P=0.000),BVD vs. BVP,r=0.683,P=0.000). Geometric mean BFM/BFD ratio in PACs was 0.77 (range:0.61-0.99),while geometric mean BVD/BVP ratio was 1.42 (range:1.13-1.79),within 95% limits of agreement. Geometric mean BFM/BFD ratio in pNETs was 0.66 (range:0.51-0.86),while geometric mean BVD/BVP ratio was 1.15 (range:0.88-1.50),within 95% limits of agreement. Conclusion sSignificantly different CT perfusion values of blood flow and blood volume were obtained by Deconvolution-based and Maximum slope+Patlak-based algorithms in the pNETs and PACs. They correlated significantly with each other. Two perfusion-measuring algorithms are interchangeable because the ranges of the conversion factors are narrow.


Fine structure and mineral components of primary calculi in some human prostates.
The fine structure of prostatic calculi has not been elucidated yet, although the chemical components were reported in detail. We studied the primary or endogenous calculi removed from eight human prostates by secondary scanning electron microscopy, backscattered electron imaging, energy-dispersive X-ray microanalysis and X-ray diffraction. The primary calculi containing Mg, Zn and S, besides Ca and P were basically classified into four stone groups (I-IV) by fine structure and mineral components. Stone I had the core deposits of calcospherites showing concentric rings and the laminated deposits concentrically around the core. Their deposits were identified as apatite. Stone II was occupied with the calcospherite deposits of apatite although the stone growth showed a rough concentric formation. Stone III contained the core of calcospherites and concentric laminated structures, similar to a smaller type of group I, whereas the wider peripheral region was deposited with needle-like structures, identified as calcium oxalates. Stone IV had the core deposits containing small hexahedral structures, identified as whitlockite, which were surrounded with several incompletely concentric laminated bands of apatite. Whitlockite crystals were also found between the fused large calculi. The initial and formative calculi were basically observed as the deposition of mineralizing spherical structures suggesting variously sized corpora amylaceous bodies. Thus, the primary prostatic calculi of stones I-III will begin from the mineralization of amylaceous bodies as a core, while the organic substances, which form stone IV, might be derived from the simple precipitation of prostatic secretion.


Design of low cost gas sensor based on SrTiO3 and BaTiO3 films.
We have prepared SrTiO3/BaTiO3 multilayer film on alumina substrates by a sol-gel technique and investigated their response for sensing ethanol vapor. The surface morphology of the films were characterized by atomic force microscope (AFM) showing that the grain size of the films increase up to 40 nm as the annealing temperature increased to 1000 degrees C. The ethanol sensors based on SrTiO3/BaTiO3 thin films were fabricated by applying interdigitated gold electrodes by sputtering technique. The ethanol sensing characteristics of SrTiO3/BaTiO3 thin films were quantified by the change in resistance of the sensors when they were exposed to ethanol. The optimum operating tempearature of these sensors was found to be 350 degrees C. In addition, the film annealed at 1000 degrees C exhibited p-type gas sensing behavior with the best sensitivity of 30-100 for low ethanol concentration in the range of 100-1000 ppm.


Modifying bis(triflimide) ionic liquids by dissolving early transition metal carbamates.
The authors report the first modification of ionic liquids with metal carbamates. A selection of homoleptic N,N-dialkylcarbamates of group 4 and 5 metals, M(O2CNR2)n, were dissolved in bis(trifluoromethylsulfonyl)imide-based ionic liquids, i.e. [bmim][Tf2N] and [P(oct)4][Tf2N], at 293 K. The resulting solutions were characterized by means of IR, UV and NMR spectroscopy, and the data were compared to those of the respective metal compounds. Notably, the dissolution process did not proceed with the release of any of the original carbamato ligands, thus preserving the intact coordination frame around the metal centre. The solvation process of Ti(O2CNiPr2)4, as a model species, in [bmim][Tf2N] was rationalized by DFT calculations. As a comparative study, solutions of NbF5 and MCl5 (M = Nb, Ta) in [bmim][Tf2N] were also investigated, revealing the possible occurrence of solvent anion coordination to the metal centres.


Transparent and Flexible Triboelectric Sensing Array for Touch Security Applications.
Tactile sensors with large-scale array and high sensitivity is essential for human-machine interaction, smart wearable devices, and mobile networks. Here, a transparent and flexible triboelectric sensing array (TSA) with fingertip-sized pixels is demonstrated by integrating ITO electrodes, FEP film, and signal transmission circuits on an undivided palm-sized polyethylene terephthalate substrate. The sensing pixels can be triggered by the corresponding external contact to induce the electrostatic potential in the transparent electrodes without power consumption, which is individually recognized by the sensor. By testing the response of the pixels, the electrical characterization is systematically investigated. The proposed TSA exhibits excellent durability, independence, and synchronicity, which is able to realize real-time touch sensing, spatial mapping, and motion monitoring. The integrated TSA has great potential for an active tactile system, human-machine interface, wearable electronics, private communication, and advanced security identification.


Small airway disease in asthma: pathophysiological and diagnostic considerations.
The aim of the current review is to summarize the evidence of small airway abnormalities in asthma, the proposed diagnostic tools for small airway abnormalities and the clinical implications of small airway abnormalities in asthma. Pathological abnormalities in the peripheral membranous bronchioles less than 2 mm in diameter (i.e. small airways) can be very frequently detected in asthma patients across severity: from mild to the more severe clinical manifestations of the disease. Interestingly, not only are small airway abnormalities present in asthma, but there is evidence that the magnitude of small airway abnormalities correlates with the severity of the disease. So far no unanimously accepted method and/or algorithm is available for small airway abnormality detection; however, some functional techniques and inflammatory markers have been used as surrogates of small airway dysfunction. Clinicians, and not only researchers, must consider small airways when approaching asthma patients, particularly when dealing with patients with a 'difficult-to-treat phenotype'. The identification of subgroups of asthma patients with prominent small airway disease is not merely speculative, and carries pathophysiological and therapeutic implications.


Comparison of Ultrasound-Guided Axillary Brachial Plexus Block Properties in Diabetic and Nondiabetic Patients: A Prospective Observational Study.
Patients with diabetes mellitus (DM) type 2 may have subclinical peripheral nerve neuropathy. We performed this study to compare the differences in duration of axillary brachial plexus blocks in patients with type 2 DM and without DM (NODM). Our hypothesis was that the sensory block duration would be prolonged in patients with DM. A total of 71 patients who were scheduled for elective forearm and/or hand surgery were enrolled in this study. Before surgery, they received ultrasound-guided axillary brachial plexus blocks with a mixture of 10 mL lidocaine 2% and 20 mL bupivacaine 0.5%. After surgery, all patients received 1 g paracetamol every 6 hours as needed. The primary end point was sensory block duration. Secondary end points were motor block duration, time until first pain (numeric rating scale [NRS] 4 or greater), highest NRS pain scores, and rescue analgesic consumption (NRS 4 or greater) through the first 2 postoperative days. In all, 67 patients completed the study: 22 in the DM group and 45 in the NODM group. Sensory and motor block durations were longer in the DM group than in the NODM group (mean [range], 773.5 [479-1155] vs 375 [113-900] minutes, and 523 [205-955] vs 300 [110-680] minutes). Time until first pain was 855 (590-1,285) minutes in the DM group and 500 (200-990) minutes in the NODM group. The highest NRS scores were also significantly lower in the DM group at 6 and 12 hours. Paracetamol consumption was lower in the DM group through the first 2 postoperative days. The presence of DM was associated with longer duration of the sensory block after axillary brachial plexus block. Therapeutic II.


Novel hydroxybutyl chitosan nanoparticles for siRNA delivery targeting tissue factor inhibits proliferation and induces apoptosis in human vascular smooth muscle cells.
Chitosan, a polysaccharide isolated from shrimp and other crustacean shells, has been widely investigated for DNA and siRNA delivery. Despite substantial effort having been made to improve chitosan as a non‑viral gene delivery vector, the application is severely limited by its poor solubility under physiological conditions. Hydroxybutyl chitosan (HBC), a modified chitosan, is soluble under neutral conditions. Tissue factor (TF) is involved in the pathogenesis of cardiovascular diseases by promoting thrombus formation and inducing the migration and proliferation of vascular smooth muscle cells. Targeting TF is an attractive therapeutic strategy for cardiovascular diseases. In the present study, the use of HBC for the transfer of TF‑siRNAs into human umbilical vein smooth muscle cells (HUVSMCs) was investigated, and the effects of TF knockdown on cell proliferation and apoptosis were examined. HBC/siRNA nanoparticles were produced by mixing HBC and siRNA solutions with the assistance of tripolyphosphate buffer. The transfection efficiency with these nanoparticles was 74±2.5%, which was determined using a fluorescence‑labeled siRNA under fluorescence microscopy. The delivery of HBC/TF‑siRNA resulted in reductions in the production of cellular and soluble TF protein in HUVMSCs, which were measured using western blotting and enzyme‑linked immunosorbent assay, respectively. TF knockdown led to inhibited cell proliferation, as assessed using a Cell Counting Kit‑8 assay, and increased cell apoptosis, determined using Annexin V‑fluorescein isothiocyanate staining. These findings suggested that HBC may be a promising vector for siRNA delivery, and that in vivo HBC/siRNA nanoparticle delivery targeting TF may be a potential option for the treatment of cardiovascular diseases, which warrants further investigation.


Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto.
Transforming growth factor beta (TGF-beta) signals regulate multiple processes during development and in adult. We recently showed that tomoregulin-1 (TMEFF1), a transmembrane protein, selectively inhibits nodal but not activin in early Xenopus embryos. Here we report that TMEFF1 binds to the nodal coreceptor Cripto, but does not associate with either nodal or the type I ALK (activin receptor-like kinase) 4 receptor in coimmunoprecipitation assays. The inhibition of the nodal signaling by TMEFF1 in Xenopus ectodermal explants is rescued with wild-type but not mutant forms of Cripto. Furthermore, we show that the Cripto-FRL1-Cryptic (CFC) domain in Cripto, which is essential for its binding to ALK4, is also important for its interaction with TMEFF1. Our results demonstrate for the first time that nodal signaling can be regulated by a novel mechanism of blocking the Cripto coreceptor.


A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis.
The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.


Risk factors for recurrent sinus surgery in cystic fibrosis: review of a decade of experience.
Patients with cystic fibrosis (CF) who undergo endoscopic sinus surgery often require multiple revision procedures. Our objective was to identify risk factors for revision sinus surgery in patients with CF, to better identify this subset of patients who might be better suited for alternative interventions at their initial procedure. Patients with CF who presented to our academic tertiary care sinus clinic between 1994 and 2003 were reviewed. Data were collected from CT scans using the Lund-Mackay scale. Data are collected on demographics, comorbidities, CF genotype, number and type of sinus surgeries, and pulmonary function tests. Eighty-one patients met inclusion criteria. Fifty patients were <18 years old at presentation. Forty-one patients were A508 homozygotes, 32 patients were A508 heterozygotes, and 5 patients were non-A508 heterozygotes. Respiratory comorbidities were asthma alone (28%) and aspirin triad (5%). Eighteen (22%) patients either smoked or lived with smokers. The mean Lund-Mackay score before the initial surgery was 16. Twenty patients were treated with medication only; 35 patients underwent 1 surgery; 14 patients underwent 2 surgeries; 8 patients underwent 3 surgeries; 2 patients underwent 4 surgeries; and 2 patients underwent 5 surgeries. Patients with higher Lund-Mackay scores at their initial CT were more likely to undergo repeat surgeries (p < 0.05). CF patients with high Lund-Mackay scores at their initial surgery are more likely to undergo several revision surgeries. These patients should be considered for more alternative initial management of their sinuses.


[Subungual glomus tumors. Apropos of 2 cases].
Glomus tumours are uncommon, though not exceptional, benign growths developed from the constituents of the "neuromyoarterial glomus" initially described by Masson. Two cases of subungual glomus tumours of the hand in middle-aged women are reported. In spite of characteristic symptoms, with paroxysmal episodes of pain triggered off by cold and the most minute traumas, and of the finding in both cases of a violine++ tumour under the nail, the condition was belatedly diagnosed (7 and 27 years respectively after the onset of symptoms). Diagnosis rested not so much on standard radiography, which showed erosion of the distal phalanx in both patients, as on arteriography of the hand which displayed a small vascular pool at the arterial stage. Tumoral excision was successful.


Identification of a specific receptor for plasmin on a group A streptococcus.
Certain group A streptococci demonstrate surface receptors that bind selectively to the key fibrinolytic enzyme, plasmin. These bacteria show no reactivity with the zymogen protein plasminogen or with other serine class proteases, such as trypsin or urokinase. Bacterium-bound plasmin retains its ability to cleave synthetic substrates and its ability to hydrolyze a fibrin clot. The bacterium-bound plasmin is not effectively regulated by its physiological regulator, alpha 2-plasmin inhibitor. This study is the first report of a bacterium-associated receptor for plasmin.


Determining factors for corneal endothelial cell loss by using bimanual microincision phacoemulsification and power modulation.
To determine risk factors for central corneal endothelial cell loss in bimanual microincision cataract surgery by using power modulation. Prospective study: 79 eyes (70 subjects) with uncomplicated bimanual cataract surgery by using power modulation. Cataracts were graded with the LOCS III system. Specular microscopy was performed preoperatively and postoperatively (5 weeks). Endothelial cell density was calculated (CD; cells/square millimeter). Endothelial cell loss (ECL = preoperative CD - postoperative CD; cells/square millimeter) and proportional loss of cells [PLC = (ECL/preoperative CD) x 100; %)] were calculated. Phacoemulsification time (seconds) and average phacoemulsification power in foot position 3 (%) were recorded. Cataracts were moderate to high density, nuclear color = 3.96, and nuclear opalescence = 3.91. Endothelial cell loss = 196 cells/square millimeter (P < 0.0001). Proportional loss of cells = 8.12% (P < 0.0001). Average phacoemulsification power in foot position 3 was low (8.17%). Increased nuclear color and opalescence were correlated with more phacoemulsification time and higher average phacoemulsification power in foot position 3 (P < 0.0001). Endothelial cell loss and proportional loss of cells, respectively, were affected by increased nuclear color (P < 0.004, P < 0.003) and opalescence (P < 0.006, P < 0.004) but were not affected by phacoemulsification time. Average phacoemulsification power in foot position 3 had a mild effect on endothelial cell loss and proportional loss of cells (P = 0.02, P = 0.02). Despite the need for longer phacoemulsification time and increased power to emulsify denser cataracts, the amount of endothelial cell loss was only mildly affected by the average phacoemulsification power in foot position 3 and unaffected by total phacoemulsification time, showing that bimanual phacoemulsification with power modulation is an efficient and effective technique for performing cataract surgery.


Eye movements to yaw, pitch, and roll about vertical and horizontal axes: adaptation and motion sickness.
In the search for parameters to predict motion sickness that can be measured in the laboratory, we performed a longitudinal investigation in aviators. Since the vestibular system is involved in the generation of motion sickness as well as eye movements, vestibulo-ocular reflex (VOR) parameters seemed relevant. We investigated three topics: 1) the effect of axis orientation and its orientation to gravity on the VOR; 2) changes in VOR parameters depending on flight experience; and 3) differences in VOR parameters in aircrew with high and low susceptibility to motion sickness. Nystagmus decay after angular velocity steps would be faster for non-susceptible and trained aviators. We recorded eye movements evoked by angular on-axis velocity steps (+/- 90 degrees x S(-2), to and from 90 degrees x S(-1)) in yaw, pitch, and roll, about both the Earth vertical and Earth horizontal axes in 14 subjects with a low susceptibility to motion sickness. These data were compared with those of 10 subjects with a high susceptibility. Horizontal axis rotations are nauseogenic. We found that during (per) and post-condition, left- and rightward rotation responses were equal, and the orientation with respect to gravity did not alter the basic nystagmus decay, apart from a sinusoidal modulation. Moreover, pitch and roll rotations show equal nystagmus decays, significantly faster than for yaw; yaw and pitch peak velocities were equal and were larger than for roll. With regard to changes in VOR parameters depending on flight experience, we found that repeated vestibular stimulation reduced nystagmus decay as well as the otolith modulation. With respect to the changes in VOR parameters and motion sickness susceptibility, we found that subjects highly susceptible to motion sickness showed a slower decay of nystagmus with a larger peak velocity than less susceptible subjects. Group averages indicate a difference in eye movement parameters, only in yaw, depending on flight experience; and between subjects with low and high susceptibility to motion sickness. The involvement of the velocity storage mechanism as realized by an internal model is given as a plausible explanation.


Low-voltage Driven Graphene Foam Thermoacoustic Speaker.
A low-voltage driven thermoacoustic speaker is fabricated based on three-dimensional graphene foams synthesized by a nickel-template assisted chemical vapor deposition method. The corresponding thermoacoustic performances are found to be related to its microstructure. Graphene foams exhibit low heat-leakage to substrates and feasible tunability in structures and thermoacoustic performances, having great promise for applications in flexible or ultrasonic acoustic devices.


Lymphoid organs function as major reservoirs for human immunodeficiency virus.
The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do not correlate with the progressive immune dysfunction characteristic of HIV infection. In this study, we have determined whether HIV-infected circulating CD4+ T lymphocytes are a correct reflection of the total pool of HIV-infected CD4+ T cells (i.e., HIV burden). To this end, HIV burden has been comparatively analyzed in peripheral blood and lymphoid tissues (lymph nodes, adenoids, and tonsils) from the same patients. The presence of HIV-1 DNA in mononuclear cells isolated simultaneously from peripheral blood and lymphoid tissues of the same patients was determined by polymerase chain reaction amplification. We found that the frequency of HIV-1-infected cells in unfractionated or sorted CD4+ cell populations isolated from lymphoid tissues was significantly higher (0.5-1 log10 unit) than the frequency in peripheral blood. Comparable results were obtained in five HIV seropositive patients in the early stages of disease and in one patient with AIDS. These results demonstrate that a heavy viral load does reside in the lymphoid organs, indicating that they may function as major reservoirs for HIV. In addition, the finding of a heavy viral load in the lymphoid organs of patients in the early stages of disease may explain the progressive depletion of CD4+ T lymphocytes and the immune dysfunction associated with the early stages of HIV infection.


Integrating Intimate Partner Violence Screening and Counseling in a Family Planning Clinic: Evaluation of a Pilot Project in Conakry, Guinea.
Few programs exist to address Intimate Partner Violence (IPV) in Guinea. In 2014, Engender Health, in partnership with the local health authorities in Conakry, Guinea, piloted an integrated approach to IPV screening and counseling, within an existing family planning clinic. This article describes both the process of formulating and implementing this approach, as well as the results of an evaluation of the program. From January to June of 2014, Engender Health staff trained midwives at the Conakry International Planned Parenthood Federation family planning clinic staff in screening and counseling client for IPV. Program evaluators used project records, interview with program staff (n=3), midwives (n=3) and client exit interviews (n=53) to measure the outcomes of this pilot project. Regardless of their IPV status, clients appreciated having a venue in which to discuss IPV. Program staff also felt empowered by the additional training and support for IPV screening. The evaluation yielded valuable suggestions for improvement, including more time for staff training and mock client interview practice, additional skills in counseling, and stronger referral links for women who screen positive for IPV. Integrating IPV screening into family planning services is an important and feasible method for reaching vulnerable women with IPV services.


Clinical potential of eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome.
Diarrhea-predominant irritable bowel syndrome (IBS-D) belongs to the group of functional gastrointestinal disorders and is characterized by abdominal pain in conjunction with diarrhea. The incidence of IBS-D is currently increasing, leading to a heavy economic burden for patients and health care systems worldwide. Recent studies suggest eluxadoline as an attractive new tool for the treatment of patients with IBS-D. Eluxadoline is an orally active μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist, with powerful antidiarrheal and analgesic activity. Eluxadoline is believed to act locally in the enteric nervous system, and has no adverse effects in the central nervous system. In this review, we discuss the most recent findings on the mechanism of action of eluxadoline and the results of the clinical trials in patients with IBS-D. We also discuss possible side effects and analyze the potential of eluxadoline to be used in the treatment of IBS-D.


Developing contents for a digital adherence tool: A formative mixed-methods study among children and adolescents living with HIV in Tanzania.
Optimal adherence (>95%) to antiretroviral treatment (ART) remains a challenge among children and adolescents living with HIV (CALHIV). Digital adherence tools (DAT) with reminder cues have proven feasible among adult people living with HIV (PLHIV), with some concerns about the risk of HIV status disclosure. We aimed to assess the needs, contents and acceptability of an SMS-based DAT among CALHIV. We first conducted a survey to understand potential barriers to using DAT among CALHIV, then tested the DAT intervention among purposively selected participants. The DAT intervention included using the Wisepill device, receiving daily reminder SMS and receiving adherence reports on how they had taken medication in the past month. The content of the reminder SMS differed over time from asking if the medication was taken to a more neutral SMS like "take care". Afterwards, we conducted exit interviews, in-depth interviews, and focus-group discussions. We analysed quantitative findings descriptively and used thematic content analysis for qualitative data. We included 142 children and 142 adolescents in the survey, and 20 of each used the intervention. Eighty-five percent (121/142) of surveyed participants indicated they would like to receive reminder SMS. Most of them (97/121-80%) of children and 94/121(78%) of adolescents would prefer to receive daily reminders. Participants who used the DAT mentioned to be happy to use the device. Ninety percent of them had good experience with receiving reminders and agreed that the SMS made them take medication. However, 25% experienced network problems. Participants preferred neutral reminder SMSs that did not mention the word 'medication', but preserved confidentiality. The provided adherence reports inspired participants to improve their adherence. None of the participants experienced unwanted disclosure or stigmatisation due to DAT. However, 5% of adolescents were concerned about being monitored daily. This study showed that DAT is acceptable and provided insight of the needed SMS content for a customized DAT for CALHIV.


n-3 polyunsaturated fatty acids suppress CD4(+) T cell proliferation by altering phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] organization.
The mechanisms by which n-3 polyunsaturated fatty acids (n-3 PUFA), abundant in fish oil, exert their anti-inflammatory effects have not been rigorously defined. We have previously demonstrated that n-3 PUFA decrease the amount of phosphatidylinositol-(4,5)-bisphosphate, [PI(4,5)P2], in CD4(+) T cells, leading to suppressed actin remodeling upon activation. Since discrete pools of PI(4,5)P2 exist in the plasma membrane, we determined whether n-3 PUFA modulate spatial organization of PI(4,5)P2 relative to raft and non-raft domains. We used Förster resonance energy transfer (FRET) to demonstrate that lipid raft mesodomains in the plasma membrane of CD4(+) T cells enriched in n-3 PUFA display increased co-clustering of Lck(N10) and LAT(ΔCP), markers of lipid rafts. CD4(+) T cells enriched in n-3 PUFA also exhibited a depleted plasma membrane non-raft PI(4,5)P2 pool as detected by decreased co-clustering of Src(N15), a non-raft marker, and PH(PLC-δ), a PI(4,5)P2 reporter. Incubation with exogenous PI(4,5)P2 rescued the effects on the non-raft PI(4,5)P2 pool, and reversed the suppression of T cell proliferation in CD4(+) T cells enriched with n-3 PUFA. Furthermore, CD4(+) T cells isolated from mice fed a 4% docosahexaenoic acid (DHA)-enriched diet exhibited a decrease in the non-raft pool of PI(4,5)P2, and exogenous PI(4,5)P2 reversed the suppression of T cell proliferation. Finally, these effects were not due to changes to post-translational lipidation, since n-3 PUFA did not alter the palmitoylation status of signaling proteins. These data demonstrate that n-3 PUFA suppress T cell proliferation by altering plasma membrane topography and the spatial organization of PI(4,5)P2.


Coherent Microwave-to-Optical Conversion via Six-Wave Mixing in Rydberg Atoms.
We present an experimental demonstration of converting a microwave field to an optical field via frequency mixing in a cloud of cold ^{87}Rb atoms, where the microwave field strongly couples to an electric dipole transition between Rydberg states. We show that the conversion allows the phase information of the microwave field to be coherently transferred to the optical field. With the current energy level scheme and experimental geometry, we achieve a photon-conversion efficiency of ∼0.3% at low microwave intensities and a broad conversion bandwidth of more than 4 MHz. Theoretical simulations agree well with the experimental data, and they indicate that near-unit efficiency is possible in future experiments.


Optimal control of greenhouse gas emissions and system cost for integrated municipal solid waste management with considering a hierarchical structure.
This study presents a synergic optimization of control for greenhouse gas (GHG) emissions and system cost in integrated municipal solid waste (MSW) management on a basis of bi-level programming. The bi-level programming is formulated by integrating minimizations of GHG emissions at the leader level and system cost at the follower level into a general MSW framework. Different from traditional single- or multi-objective approaches, the proposed bi-level programming is capable of not only addressing the tradeoffs but also dealing with the leader-follower relationship between different decision makers, who have dissimilar perspectives interests. GHG emission control is placed at the leader level could emphasize the significant environmental concern in MSW management. A bi-level decision-making process based on satisfactory degree is then suitable for solving highly nonlinear problems with computationally effectiveness. The capabilities and effectiveness of the proposed bi-level programming are illustrated by an application of a MSW management problem in Canada. Results show that the obtained optimal management strategy can bring considerable revenues, approximately from 76 to 97 million dollars. Considering control of GHG emissions, it would give priority to the development of the recycling facility throughout the whole period, especially in latter periods. In terms of capacity, the existing landfill is enough in the future 30 years without development of new landfills, while expansion to the composting and recycling facilities should be paid more attention.


Affordance in Socio-Material Networks: A Mixed Method Study of Researchers' Groups and Analog-Digital Objects.
In this paper, we argue that we can better understand the relationship between social interaction and materiality by linking qualitative analysis of analog and digital practices, adopting Basov's model of socio-material networks. Our research questions turn about the interrogation of how social links distress the usage of analog and digital objects by researchers. We consider scientific networks with the relationship between researchers and their tools as a three-level social material network. It sheds light on how different types of researchers position their engagement with analog and digital materiality over time and its affordance and emotional attachment. This study contributes to the understanding of researchers' practices that involve new and old techniques and specific and not-specific tools.


APOA5 Ala315>Val, identified in patients with severe hypertriglyceridemia, is a common mutation with no major effects on plasma lipid levels.
The importance of the apolipoprotein A5 (APOA5) gene in determining plasma triglyceride (TG) levels has been demonstrated in transgenic and knockout mice and confirmed by human association studies in different ethnic groups. We screened for nonsynonymous APOA5 mutations in patients with plasma TG levels >10 mmol/L. The coding sequence and promoter region of the APOA5 gene were sequenced in 95 individuals with severe hypertriglyceridemia (HTG). A large population sample of 3,202 individuals was screened by PCR and restriction analysis for presence of detected mutation. In total, three heterozygous carriers of 944C>T (Ala315>Val) were identified in the severe HTG patients, while 22 carriers were identified in the population sample. The rare allele frequency of the Val315 was significantly higher in the HTG sample than in controls (0.016 vs. 0.003, p<0.01, respectively). Most of the control Ala315Val carriers, however, had plasma lipid levels (TGs, total cholesterol and high-density lipoprotein cholesterol) within the usual range detected in the population. APOA5 Ala315>Val does not play any dominant/important role in the genetic determination of plasma TG levels, but the increased frequency in HTG patients compared to controls suggests that it might interact with other gene variants to cause HTG.


Modeling temperature-dependent survival with small datasets: insights from tropical mountain agricultural pests.
Many regions are increasingly threatened by agricultural pests but suffer from a lack of data that hampers the development of adequate population dynamics models that could contribute to pest management strategies. Here, we present a new model relating pest survival to temperature and compare its performance with two published models. We were particularly interested in their ability to simulate the deleterious effect of extreme temperatures even when adjusted to datasets that did not include extreme temperature conditions. We adjusted the models to survival data of three species of potato tuber moth (PTM), some major pests in the Tropical Andes. To evaluate model performance, we considered both goodness-of-fit and robustness. The latter consisted in evaluating their ability to predict the actual altitudinal limits of the species in the Ecuadorian Andes. We found that even though our model did not always provide the best fit to data, it predicted extreme temperature mortality and altitudinal limits accurately and better than the other two models. Our study shows that the ability to accurately represent the physiological limits of species is important to provide robust predictions of invasive pests' potential distribution, particularly in places where temperatures approach lethal extremes. The value of our model lies in its ability to simulate accurate thermal tolerance curves even with small datasets, which is useful in places where adequate pest management is urgent but data are scarce.


Congenital peribronchial myofibroblastic tumor: comparison of fetal and postnatal morphology.
Congenital peribronchial myofibroblastic tumor (CPMT) is a solid pulmonary tumor found in fetuses and neonates with pathology characterized by a proliferation of bland spindled cells with or without irregular cartilaginous islands. It has previously been reported in the literature as a fibrosarcoma, leiomyosarcoma, and hamartoma, among other names. Although complications such as fetal hydrops can occur, the prognosis is generally good if the infant can survive long enough for mass resection. We present a case of a CPMT resected by antenatal fetal surgery at 23 weeks in gestation, with additional tumor resected following birth when the infant was 6 weeks of age. The pathology of this lesion showed a marked increase in the cartilaginous component after birth as well as a decrease in cellularity and mitotic activity. This case presents a unique opportunity to examine the progression of a congenital tumor excised by prenatal and postnatal resections.


Valaciclovir versus aciclovir for the treatment of primary genital herpes simplex: a cost analysis.
The current guidelines for the treatment of primary herpes simplex in the Genito-urinary department in Sheffield Teaching Hospitals NHS Foundation Trust, recommend valaciclovir as a first-line medication. This is a prodrug of aciclovir, which has been used for many years as a treatment for primary herpes simplex virus. The basis of the recommendation largely relates to valaciclovir being more bioavailable than aciclovir. However, there is no evidence to suggest this has an effect on overall outcome with regard to symptom control and viral shedding. The purpose of the service evaluation was to discover if significant cost savings could be made by changing the prescribing policy to make aciclovir the drug of choice for primary herpes simplex virus. Based on 160 patients receiving valaciclovir (500 mg BD) during April 2013 and March 2014, if they had been treated with aciclovir (400 mg TDS) instead, a saving of £828.80 (66% reduction) could have been made.


Associations between Uric Acid Level and 3-Month Functional Outcome in Acute Ischemic Stroke Patients Treated with/without Edaravone.
Uric acid (UA), an antioxidant with neuroprotective effects, favorably affects stroke outcome. However, the effect has not been examined in patients treated with edaravone, a frequently used free radical scavenger. We investigated whether the use of edaravone affected the relationship between UA levels and outcome in acute ischemic stroke. We retrospectively evaluated 1,114 consecutive ischemic stroke patients with premorbid modified Rankin Scale (mRS) scores <2 admitted within 24 h of onset (mean, 74 years; median UA levels, 333 μmol/L). We divided the patients into 2 groups using the median UA value as a cutoff, a low UA group (≤333 μmol/L; n = 566) and a high UA group (>333 μmol/L; n = 548), and compared their clinical characteristics and favorable outcomes (mRS <2) at 90 days. We investigated the associations between UA levels and 90-day stroke outcome in patients with and without edaravone treatment. The high UA group had a higher proportion of men, hypertension, atrial fibrillation, and cardioembolic stroke than the low UA group. The high UA group also had a higher proportion of patients with mRS <2 at 90 days (61.5 vs. 54.1%, p = 0.013), but the significance was diminished in multivariate analysis (OR 1.30, 95% CI 0.94-1.71). In subgroup analysis, the high UA group without edaravone exhibited a higher proportion of patients with mRS <2 at 90 days than the low UA group (OR 2.87, 95% CI 1.20-7.16). The high UA group with edaravone did not exhibit this difference. In acute ischemic stroke, the favorable association between high UA levels and outcome at 90 days was not evident in patients treated with edaravone.


Evaluation and treatment of female stress urinary incontinence after pelvic radiotherapy.
Pelvic radiotherapy is associated with both acute and chronic voiding dysfunction. A review of the success and complications of surgical treatments for female stress urinary incontinence after pelvic radiotherapy has not been summarized in the published literature. A systematic review of female stress urinary incontinence after pelvic radiotherapy was conducted using MeSH terminology (1988-2018). There is limited published literature on the treatment of stress urinary incontinence in women following pelvic radiotherapy. Long term indwelling urethral catheter should be avoided in all women given the risk of iatrogenic hypospadias. Surgical treatments can be classified into those for the intact versus failed outlet. Urethral bulking injections have been studied in a prospective fashion specifically in women with stress urinary incontinence after radiotherapy and although not randomized, have the highest level of evidence. Patients should be screened for a history of prior radiotherapy before considering sling placement. Artificial urinary sphincter is associated with a high rate of erosion after prior radiotherapy. The role of Burch colposuspension in patients with prior radiotherapy is poorly defined. Urinary diversion should be considered for patients with a devastated outlet. Since the long-term effects of radiotherapy on lower urinary tract voiding function are typically irreversible and progressive, further research is needed to mitigate the adverse effects of irradiation and identify more durable treatment options for women with radiation induced bladder dysfunction and stress urinary incontinence.


Evaluation of psycho-social support to parents with an infant born preterm.
The birth of a preterm child is a trauma that causes crisis reactions in parents. The hypothesis was that parents need psycho-social support in order to manage this trauma. Psycho-social support was defined as both medical and social information, processing the emotional feelings, social support and starting the bonding process. The aim of the study was to explore the type and frequency of psycho-social support to parents of preterm children born during 1991, 1994 and 1997 in a Swedish university hospital. 47 parents answered a questionnaire based on previous focus group interviews. The children were born in gestation weeks 23-7. Medical and social information was more frequent during the first period of intensive care than later on during the care process. Contact frequency concerning feelings and emotional reactions was low and decreased over time. All parents were helped to start the bonding process. One-third of the parents reported long-term psychological problems due to the birth of the preterm child, while only a few reported financial (15%), practical (13%) or social (9%) long-term problems. Conclusions were that from a crisis theory perspective psycho-social support, defined as regular medical information also ought to be initiated later on in the care process and that increased emotional support concerning crisis reactions is desirable in order to process the feelings raised by the trauma.


Effects of spatial heterogeneity on the dynamics of a microbial feeding interaction.
A mathematical model for an ideal chemostat in which one microbial population feeds on another and where Monod's model is used for the specific growth rates of both populations predicts a less stable behavior for the system than the one observed experimentally. Various factors have been proposed as being the reason for the increased stability of such systems. In this work, the effect of spatial heterogeneity on the dynamics of the microbial feeding interaction is studied. It is concluded that spatial heterogeneity has a stabilizing effect on the system. This effect combined with other factors could be the reason for the increased stability observed in systems where a microbial feeding interaction occurs.


Acute lymphangitis treated by moxibustion with garlic in 118 cases.
TCM holds that acute lymphangitis is pathogenically caused by the accumulated internal fire and toxicity, and the external skin injury-induced infection, leading to toxicity going upward along the meridians. The treatment should be given to clear away heat and toxin. Blood letting by a three-edged needle may promote qi and blood circulation and remove the toxic heat. Garlic has the function of antagonizing Staphylococcus aureus, Bacillus dysenteriae and various kinds of bacteria. Since the volatile oil in moxa is antagonistic to bacteria, the burning moxa can also promote the local flow of qi and blood, and enhance the antagonistic effect of garlic on bacteria. Therefore, satisfactory curative results can be achieved by the therapy.


[Almindeligt Hospital -- a large and considerable building].
In the year 1769 a newly erected big public institution was inaugurated in Copenhagen. It was built to accommodate 700 paupers. 200 out of these, who were unable to look after themselves, were given full board, while the others had to pay for their meals out of money they gained by doing the odd jobs in or outside the institution. A small infirmary of 16 beds had in 1790 grown to 154 beds and in 1807 to more than 400. In addition to the care of patients with chronic diseases, the public treatment of syphilis and scabies now had to be attended to. In 1808 the infirmary was divided into two units, one medical and one surgical. It was not until 1855 that a department for venerea and skin diseases was established. In 1845 1500 persons lived in the buildings: 110 employees, 1074 paupers and 316 patients. These packed crowds and bad sanitary conditions led to disaster when the cholera epidemic broke out in 1853. Consequently the Copenhagen Municipal Hospital was built and in 1863 most of the patients from the institution were transferred to this hospital. Nevertheless, in 1890, 1700 paupers and disabled patients still remained in the crowded old buildings. In 1892 it was decided that the entire institution whould move to new premises in Nørre Alle, the present Old Peoples Home. The following year the old buildings were demolished.


Effect of ammonium ion, inorganic phosphate and amino acids on the biosynthesis of protylonolide, a precursor of tylosin aglycone.
The production of tylosin by Streptomyces fradiae KA-427 in a defined medium was inhibited by ammonium ions and by inorganic phosphate. The production of protylonolide, an early lactonic intermediate of tylosin biosynthesis with the same carbon skeleton as tylosin aglycone, by a mutant of strain KA-427 was also reduced by these two kinds of ions. In contrast, the bioconversion of protylonolide to tylosin by another mutant was less susceptible to ammonium ions but was sensitive to inorganic phosphate. The addition of protylonolide to a culture of S. fradiae KA-427 increased the tylosin yield, suggesting that aglycone synthesis is limiting under the conditions used. When L-valine, L-leucine, L-isoleucine, L-threonine, or the corresponding 2-keto acid was added to the culture medium, the protylonolide titer increased. The addition of [14C]valine gave rise to [14C]protylonolide. 13C NMR spectroscopic analysis revealed that iso-butyrate, which is a valine metabolite, was incorporated into protylonolide at the carbons known to originate from propionate and n-butyrate. Taking account of these findings, the regulation of tylosin biosynthesis in S. fradiae by ammonium ion is discussed in relation to amino acid metabolism.


Passive near-field imaging with pseudo-thermal sources.
We demonstrate experimentally that spurious effects caused by interference can be eliminated in passive near-field imaging by implementing a simple random illumination. We show that typical imaging artifacts are effectively eliminated when the radiation emitted by a pseudo-thermal source illuminates the sample and the scattered field is collected by an aperture probe over essentially all angles of incidence. This novel pseudo-thermal source can be easily implemented and significantly enhances the performance of passive near-field imaging.


[Effect of several biologically active substances on the reactivity and immune response of the body].
Experiments were carried out with a total of 140 guinea pigs to study the effect of a tissue emulsion of swine embryos on some of the general defense reactions, the cell and humoral immunity of the organism in the treatment with an intact and a killed (with 3 per cent formalin) vaccine produced with two strains of Salmonella abortus ovis. Investigated were the phagocytic activity of the lung macrophages and the immobile cells of the reticulo-endothelial system in the spleen and the liver, the protein spectrum, the blood serum level of properdine, and the histologic changes in the parenchymal organs of the test animals. It was found that the application of a tissue emulsion simultaneously with the injection of the animals with an anti-Salmonella vaccine raised the unspecific reactivity of the organism. This was expressed with the rise of the gammaglobulin and properdine levels of the blood serum and the change in the immunologic pattern of the organism, an increase in the phagocytic activity of lung macrophages and RES immobile cells from 16 to 25 per cent, and the titer of agglutinins--from 10 to 32 times. Highest agglutinin titers of the blood and most active phagocytic defense were reached with the use of a vaccine having a whole antigen, combined with a tissue emulsion.


Spatially resolved single-shot absorption spectroscopy with x-ray free electron laser pulse.
A new method of spatially resolved single-shot absorption spectroscopy for an x-ray free electron laser (XFEL) pulse has been developed by using a dispersive spectrometer and an elliptical mirror to enhance the spatial resolution. As a demonstration, we performed x-ray absorption near-edge structure measurement of Cu with a pump-probe scheme combining an XFEL pulse and a high-power femtosecond laser pulse. In the experiment, changes of an absorption spectrum in a plasma generated with a laser shot were successfully observed. The method will be a powerful tool for experiments requiring a spatial resolution and/or a single-shot measurement, such as high energy density science using a high-power laser pulse.


[Brain glioma complicated by subdural hematoma].
A case is reported in which chronic subdural haematoma developed in association with a glioma of the left temporal lobe. The stroke-like onset of symptoms one month before surgical intervention, encapsulated liquid subdural haematoma, necrotic cerebral cortex over the tumour and easily bleeding peripheral parts of the tumour suggested a primary haemorrhage into the peripheral part of the tumour followed by penetration of the haematoma into the subdural space.


Role of Dapagliflozin and Liraglutide on Diabetes-Induced Cardiomyopathy in Rats: Implication of Oxidative Stress, Inflammation, and Apoptosis.
The current study aims to assess the protective effects of dapagliflozin (Dapa; a sodium-glucose cotransporter-2 inhibitor) and/or liraglutide (Lira; a glucagon-like peptide 1 agonist) in an experimental model of diabetic cardiomyopathy (DCM). A single dose of streptozotocin (STZ) was administrated to male Sprague-Dawley rats by intraperitoneal injection at a dose of 50 mg/kg to induce diabetes mellitus (DM). Dapa (1 mg/kg, orally), Lira (0.4 mg/kg, s.c.), and Dapa-Lira combination were administrated for 8 weeks once-daily. Blood samples were evaluated for glucose level and biochemical markers of cardiac functions. Cardiac tissue was dissected and assessed for redox homeostasis (malondialdehyde (MDA), glutathione (GSH), and catalase (CAT)), pro-inflammatory mediators (NF-κB and tumor necrosis factor-α (TNF-α)), and apoptotic effectors (caspase-3). Moreover, the effect of treatments on the cardiac cellular structure was studied. Dapa and/or Lira administration resulted in significant improvement of biochemical indices of cardiac function. Additionally, all treatment groups demonstrated restoration of oxidant/antioxidant balance. Moreover, inflammation and apoptosis key elements were markedly downregulated in cardiac tissue. Also, histological studies demonstrated attenuation of diabetes-induced cardiac tissue injury. Interestingly, Dapa-Lira combination treatment produced a more favorable protective effect as compared to a single treatment. These data demonstrated that Dapa, Lira, and their combination therapy could be useful in protection against DM-accompanied cardiac tissue injury, shedding the light on their possible utilization as adjuvant therapy for the management of DM patients.


Unsupervised method for extracting machine understandable medical knowledge from a large free text collection.
Definitions of medical concepts (e.g diseases, drugs) are essential background knowledge for researchers, clinicians and health care consumers. However, the rapid growth of biomedical research requires that such knowledge continually needs updating. To address this problem, we have developed an unsupervised pattern learning approach that extracts disease and drug definitions from automatically structured randomized clinical trial (RCT) abstracts. In addition, each extracted definition is semantically classified without relying on external medical knowledge. When used to identify definitions from 100 manually annotated RCT abstracts, our medical definition knowledge base has precision of 0.97, recall of 0.93, F1 of 0.94 and semantic classification accuracy of 0.96.


Histiocytosis X of the hypothalamus.
An 18-year-old woman presented with visual disturbance and endocrine dysfunction (diabetes insipidus, delayed puberty, hypothyroidism, hypoadrenalism, and hyperprolactinemia). Computed tomography and enhanced cisternography showed a single hypothalamic mass, which proved at biopsy to be histiocytosis X. Further studies showed the disease to be restricted to the hypothalamus. The patient was treated with hormonal replacement therapy, but her visual acuity continued to worsen. Visual acuity improved after low-dose irradiation of the pituitary fossa and hypothalamus, which also led to disappearance of the mass. This case shows that localized hypothalamic histiocytosis X can be diagnosed and treated successfully before other systems become involved.


Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells.
Leukotrienes (LTs) are potent lipid mediators involved in the control of host defense. LTB(4) induces leukocyte accumulation, enhances phagocytosis and bacterial clearance, and increases NO synthesis. LTB(4) is also important in early effector T cell recruitment that is mediated by LTB(4) receptor 1, the high-affinity receptor for LTB(4). The aims of this study were to evaluate whether LTs are involved in the secondary immune response to vaccination in a murine model of Histoplasma capsulatum infection. Our results demonstrate that protection of wild-type mice immunized with cell-free Ags from H. capsulatum against histoplasmosis was associated with increased LTB(4) and IFN-gamma production as well as recruitment of memory T cells into the lungs. In contrast, cell-free Ag-immunized mice lacking 5-lipoxygenase(-/-), a critical enzyme involved in LT synthesis, displayed a marked decrease on recruitment of memory T cells to the lungs associated with increased synthesis of TGF-beta as well as IL-10. Strikingly, these effects were associated with increased mortality to 5-lipoxygenase(-/-)-infected mice. These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis.


Synthesis and exchange reactions of Ni-dimine-COD, acetylene and olefin complexes.
The complexes MesDADNi(COD) (1), DippDADNi(COD) (2), DippDABNiCOD (3) and DippBIANNi(COD) (5) were readily prepared from Ni(COD)(2). The analogous reaction of the ligand MesBIAN afforded (MesBIAN)(2)Ni (4). The related Ni alkyne complexes DADNi(PhC[triple bond]CPh) (6), DippDABNi(PhC[triple bond]CPh) (7) and DippBIANNi(PhC[triple bond]CPh) (8) are readily prepared by addition of alkyne to solutions of the COD species. The analogous reactions employing tBuDAD ligand with either Ni(COD)(2) alone or Ni(COD)(2) and PhC[triple bond]CPh led only to the known bis-ligand Ni complex, although tBuDADNi(MeCO(2)C[triple bond]CCO(2)Me) (9) is readily prepared. In a similar fashion, the species DippDADNi(MeCO(2)C[triple bond]CCO(2)Me) (10), DippDABNi(Me(3)SiC[triple bond]CSiMe(3)) (11), DippDABNi(MeCO(2)C[triple bond]CCO(2)Me) (12) and DippBIANNi(MeCO(2)C[triple bond]CCO(2)Me) (13) were prepared. Reactions with olefins afforded DippDABNi(MeCO(2)CH=CHCO(2)Me) (14), DippDABNi(MeCO(2)CH=CHPh) (15). Employing isolated (3) or (15) in exchange reactions afforded (7), (11) (14) and (15). Similarly (6) served as a precursor to (10) while (11) reacts with PhC[triple bond]CPh to give (7). The solid state structures of (1), (3)-(7), (9), (11) and (15) are reported.


Na+/K(+)-ATPase in rat brain and erythrocytes as a possible target and marker, respectively, for neurotoxicity: studies with chlordecone, organotins and mercury compounds.
Due to the inaccessibility of human nerve tissue for direct biochemical evaluation, there appears to be a need to identify peripheral markers which will reflect toxicity to the central nervous system by relatively non-invasive means. The aim of this study was to investigate whether the enzyme Na+/K(+)-ATPase in erythrocytes could be used as a marker for effects on the same enzyme in brain tissue. The compounds chosen to test this hypothesis were the pesticide chlordecone, the organotin compounds triethyltin and tributyltin, mercuric chloride and methyl mercury. All compounds were found to inhibit in vitro Na+/K(+)-ATPase activity in rat brain (IC50s = 0.9-56 microM) and in rat erythrocytes (IC50s = 1.2-66 microM) with similar potencies. However, administration of these compounds in vivo at high doses produced no significant inhibition of either brain or erythrocyte Na+/K(+)-ATPase activity, despite observed symptoms of neurotoxicity. Dialysis experiments indicated that dissociation of the compounds by dilution during tissue preparation was not responsible for the lack of detectable in vivo inhibition. Measurements of metal concentrations in brain by atomic absorption spectrometry after in vivo administration of triethyltin, mercuric chloride and methyl mercury indicated that levels of these compounds were too low to inhibit significantly NA+/K(+)-ATPase activity. These results suggest that inhibition of Na+/K(+)-ATPase activity might not represent the mechanism responsible for the neurotoxicity of these compounds, and that erythrocyte Na+/K(+)-ATPase activity is not a useful marker for neurotoxicity following acute exposures.


Crustacean-acanthocephalan interaction and host cell-mediated immunity: parasite encapsulation and melanization.
Host-parasite interactions of Pomphorhynchus laevis (Müller, 1776) in naturally infected amphipod, Echinogammarus stammeri (Karaman), from the Brenta River (northern Italy) are described. A fully developed acanthocephalan larva occupies a large portion of an amphipod's haemocoelic space; thus, the parasite frequently induces displacement of host digestive tract and other internal organs. However, no apparent damage to the host's internal structures was observed. Within the haemocoel of E. stammeri, each larva of P. laevis is surrounded with a membranous layer, formed by microvilli, which maintains intimate contact with the amphipod's internal organs and haemocytes. Three types of circulatory haemocytes were identified based upon their distinct appearance: hyaline cell, semi-granular cell and granular cell. Echinogammarus stammeri haemocytes surrounded acanthocephalan larvae and in some instances a partially and/or totally melanized P. laevis larva was noticed. Interestingly, no melanized larvae were found in E. stammeri parasitized with other acanthocephalans namely Echinorhynchus truttae (Schrank, 1788), Polymorphus minutus (Goeze, 1782) and Acanthocephalus clavula (Dujardin, 1845).


Soft Wetting: Droplet Receding Contact Angles on Soft Superhydrophobic Surfaces.
Despite intensive investigations on the droplet receding contact angle on superhydrophobic surfaces, i.e., a key parameter characterizing surface wettability and adhesion, the quantitative correlation between the surface structure mechanical properties (softness) and the droplet receding contact angles remains vague. By systematically varying the geometric dimensions and mechanical properties of soft pillar arrays, we find that the droplet receding contact angles decrease with the decrease in the pillar spring constant. Most surprisingly, the densely packed pillar arrays may result in larger receding contact angles than those on sparsely packed pillars, opposing the understanding of rigid pillar arrays, where the receding contact angles increase with a decrease in the packing density of pillars. This is attributed to the collective effects of capillarity and elasticity, where the energy consumed by the sliding contact line, the energy stored in the distorted liquid-vapor interface, and the energy stored in the deflected pillar contribute to the droplet depinning characteristics. We develop an analytical model to predict the droplet receding contact angles on soft superhydrophobic pillar arrays with knowledge of the material intrinsic receding contact angle, the pillar geometry, and the pillar mechanical properties. The predictions are corroborated by the experimental data measured in this and prior studies.


The Utility of the HSAB Principle via the Fukui Function in Biological Systems.
The hard/soft acid-base principle has long been known to be an excellent predictor of chemical reactivity. The Fukui function, a reactivity descriptor from conceptual density functional theory, has been shown to be related to the local softness of a system. The usefulness of the Fukui function is explored and demonstrated herein for three common biological problems: ligand docking, active site detection, and protein folding. In each type of study, a scoring function is developed based on the local HSAB principle using atomic Fukui indices. Even with necessary approximations for its use in large systems, the Fukui function remains a useful descriptor for predicting chemical reactivity and understanding chemical systems.


Position of Correct Option and Distractors Impacts Responses to Multiple-Choice Items: Evidence From a National Test.
Even though the impact of the position of response options on answers to multiple-choice items has been investigated for decades, it remains debated. Research on this topic is inconclusive, perhaps because too few studies have obtained experimental data from large-sized samples in a real-world context and have manipulated the position of both correct response and distractors. Since multiple-choice tests' outcomes can be strikingly consequential and option position effects constitute a potential source of measurement error, these effects should be clarified. In this study, two experiments in which the position of correct response and distractors was carefully manipulated were performed within a Chilean national high-stakes standardized test, responded by 195,715 examinees. Results show small but clear and systematic effects of options position on examinees' responses in both experiments. They consistently indicate that a five-option item is slightly easier when the correct response is in A rather than E and when the most attractive distractor is after and far away from the correct response. They clarify and extend previous findings, showing that the appeal of all options is influenced by position. The existence and nature of a potential interference phenomenon between the options' processing are discussed, and implications for test development are considered.


Steroid injection in lateral epicondylar pain.
What is the evidence for using steroid injection to treat lateral epicondylar pain in the general practice setting? In reviewing four randomised controlled trials, this article concludes that steroid injection is indicated if rapid pain relief is desired in the short term. The evidence for steroid injection in the long term is less clear.


Molecular data reveal a tropical freshwater origin of Naidinae (Annelida, Clitellata, Naididae).
The phylogenetic relationships within Naidinae (Annelida, Clitellata, Naididae) were investigated, using six molecular markers, both mitochondrial (12S rDNA, 16S rDNA, the COI gene) and nuclear (18S rDNA, 28S rDNA, the ITS region). Thirty-seven nominal species, representing 16 of the 22 genera recognized in the subfamily, were included, and the Nais communis/variabilis species complex was represented by six different morphotypes. Ten other species of Naididae were selected as outgroups. The data were analysed by Bayesian inference and Maximum Likelihood. The phylogeny corroborates monophyly of the Naidinae, and the separate status of the genus Pristina (Pristininae) and the Opistocystinae. Relationships within Naidinae are largely well supported, but in some parts unexpected: (1) A clade containing the largely tropical genera Dero and Branchiodrilus is sister to the rest of the subfamily, and together with a third tropical genus, Allonais, they form a basal paraphyly. All these genera show morphological adaptations to environmental hypoxia, leading to the conclusion that Naidinae originated in tropical freshwaters. (2) The genera Dero, Nais and Piguetiella are paraphyletic. (3) At least Branchiodrilus, Paranais, Chaetogaster, Nais, Stylaria appear to contain cryptic species. Morphological characters, especially those associated with chaetae, are to a great extent homoplastic within Naidinae, which certainly has contributed to the overall taxonomic confusion of this subfamily.


Intradiscal electrothermal therapy (IDET): a viable alternative to surgery for low back pain in workers' compensation patients?
This prospective study was conducted to evaluate improvements in pain and disability in a series of 53 consecutive worker's compensation patients with discogenic low back pain following treatment with the intradiscal electrothermal therapy (IDET) procedure. Between 2002 and 2004, a total of 53 consecutive patients, who were claimants of worker's compensation, were treated using IDET for their discogenic low back pain. The outcomes of these patients were analyzed statistically for the current study by physical exam and self-assessment questionnaires of pain and disability at baseline and at 24-months post-procedure. Pain and disability outcomes were assessed by visual analog pain score (VAS) on a 0-100 mm scale and Oswestry Disability Index respectively. The mean patient age was 41.83 years (range 20 to 61 years). Caucasians (53 %), African-Americans (30%), and Hispanics (17%) formed the majority of population. Forty-nine percent were using narcotic pain medications at the time of initial assessment. The first definitive end point was considered at 24 months after the procedure. Median follow-up period was 56 months (range 29-72 months). A mean reduction (p < 0.001) of 63% in the VAS score and 70% in the Oswestry scores was noted after IDET. The patient's initial VAS and Oswestry scores (p < 0.05) significantly affected the final outcomes. Forty-seven percent of the patients returned to some degree of economic productivity and only seven (initial 26) consumed narcotic analgesics. IDET procedure can be a useful, safe and cost-effective option in the management of carefully selected workers' compensation claimants with chronic low back pain of discogenic etiology.


Regulation of luteinizing hormone subunit biosynthesis in cultured male anterior pituitary cells: effects of gonadotropin-releasing hormone and testosterone.
The purpose of this study was to evaluate the direct effects of testosterone (T) on LH subunit apoprotein synthesis, glycosylation, and release by the male pituitary. Cells from 1-week castrate rats were cultured for 48 h in steroid-free medium, followed by 48 h in medium with or without 10 nM T. The cells were then incubated for 2, 4, 6, 8, or 12 h in medium containing [35S]methionine (35S-Met) or [3H]glucosamine (3H-Gln), with or without 1 nM GnRH (Exp 1) or in medium containing precursors with or without 10 nM T and/or 1 nM GnRH (Exp 2). Radiolabeled precursor incorporation into LH subunits was determined by immunoprecipitation, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In Exp 1, precursor incorporation into total protein (TP) and LH subunits increased linearly over time for at least 8 h. GnRH did not affect precursor incorporation into total protein or 35S-Met labeling of LH subunits, but stimulated a linear time-dependent accumulation of 3H-Gln into total (cells plus media) LH subunits and release of radioimmunoassayable LH into the medium. Based on these results, the effects of T on LH subunit biosynthesis (with or without GnRH) were studied during an 8-h incubation. In Exp 2, GnRH enhanced total 3H-Gln (but not 35S-Met) incorporation into both LH subunits. GnRH stimulated the release of 35S-Met LH alpha and 3H-Gln LH subunits and increased the relative glycosylation of secreted LH subunits without altering the relative glycosylation of intracellular LH subunits. T inhibited radioimmunoassayable LH release and incorporation of both precursors into total and secreted LH subunits (with or without GnRH). However, only the relative glycosylation of secreted LH alpha was reduced by T (with or without GnRH). These data indicate that T acts directly at the pituitary to inhibit LH subunit apoprotein synthesis and selectively inhibit LH alpha glycosylation. Further, these data support the hypothesis that changes in LH glycosylation may be one of the ways by which GnRH and T regulate LH release.


Ruthenium Metallotherapeutics: Novel Approaches to Combatting Parasitic Infections.
Human parasitic infections cause a combined global mortality rate of over one million people per annum and represent some of the most challenging diseases for medical intervention. Current chemotherapeutic strategies often require prolonged treatment, coupled with subsequent drug-induced cytotoxic morbidity to the host, while resistance generation is also a major concern. Metals have been used extensively throughout the history of medicine, with more recent applications as anticancer and antimicrobial agents. Ruthenium metallotherapeutic antiparasitic agents are highly effective at targeting a range of key parasites, including the causative agents of malaria, trypanosomiasis, leishmaniasis, amoebiasis, toxoplasmosis and other orphan diseases, while demonstrating lower cytotoxicity profiles than current treatment strategies. Generally, such compounds also demonstrate activity against multiple cellular target sites within parasites, including inhibition of enzyme function, cell membrane perturbation, and alterations to metabolic pathways, therefore reducing the opportunity for resistance generation. This review provides a comprehensive and subjective analysis of the rapidly developing area of ruthenium metal- based antiparasitic chemotherapeutics, in the context of rational drug design and potential clinical approaches to combatting human parasitic infections.


Recent advances in optical imaging through deep tissue: imaging probes and techniques.
Optical imaging has been essential for scientific observations to date, however its biomedical applications has been restricted due to its poor penetration through tissues. In living tissue, signal attenuation and limited imaging depth caused by the wave distortion occur because of scattering and absorption of light by various molecules including hemoglobin, pigments, and water. To overcome this, methodologies have been proposed in the various fields, which can be mainly categorized into two stategies: developing new imaging probes and optical techniques. For example, imaging probes with long wavelength like NIR-II region are advantageous in tissue penetration. Bioluminescence and chemiluminescence can generate light without excitation, minimizing background signals. Afterglow imaging also has high a signal-to-background ratio because excitation light is off during imaging. Methodologies of adaptive optics (AO) and studies of complex media have been established and have produced various techniques such as direct wavefront sensing to rapidly measure and correct the wave distortion and indirect wavefront sensing involving modal and zonal methods to correct complex aberrations. Matrix-based approaches have been used to correct the high-order optical modes by numerical post-processing without any hardware feedback. These newly developed imaging probes and optical techniques enable successful optical imaging through deep tissue. In this review, we discuss recent advances for multi-scale optical imaging within deep tissue, which can provide reseachers multi-disciplinary understanding and broad perspectives in diverse fields including biophotonics for the purpose of translational medicine and convergence science. Methodologies for multi-scale optical imaging within deep tissues are discussed in diverse fields including biophotonics for the purpose of translational medicine and convergence science. Recent imaging probes have tried deep tissue imaging by NIR-II imaging, bioluminescence, chemiluminescence, and afterglow imaging. Optical techniques including direct/indirect and coherence-gated wavefront sensing also can increase imaging depth.


Effect of Abrupt Discontinuation of Antidepressants in Critically Ill Hospitalized Adults.
To determine whether discontinuation of chronic antidepressant therapy is associated with a higher risk of antidepressant discontinuation syndrome (ADS) symptoms in patients admitted to the intensive care unit (ICU) when compared with those who were continued on therapy and to identify factors associated with increased risk of ADS in this population. Single-center retrospective observational cohort study. ICUs in a tertiary care hospital. A total of 106 adult patients, admitted to the ICU between September 2013 and August 2014, who had a length of stay of 72 hours or longer and who were receiving chronic selective serotonin inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) before admission. Patients were classified as continued or discontinued from therapy based on initiation of home SSRI/SNRI therapy within 48 hours of admission. The primary end point was incidence of ADS symptoms. Type of symptoms, receipt of symptom-related therapies, and length of stay were also assessed. Sequential logistic regression analysis was used to determine the impact of discontinuation while controlling for other risk factors. Therapy was discontinued in 38.7% of patients. The risk of developing ADS symptoms was higher in discontinued patients (unadjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.12-6.07, p=0.024). After adjusting for covariates, the odds of ADS increased (adjusted OR 3.8, 95% CI 1.3-11.7, p=0.018). Female sex was associated with an increase in risk of ADS (OR 3.4, 95% CI 1.2-10.0, p=0.026). Affective symptoms were the most prevalent type reported (34.1% vs 10.8%, p=0.005). Use of symptom-related therapies and length of stay did not differ between groups. Abrupt discontinuation of SSRI/SNRI therapy increases the risk of ADS symptoms in critically ill patients, particularly in females. These results underscore the importance of continuation of home antidepressant therapy even in the setting of critical illness.


Measuring patient-reported outcomes: moving beyond misplaced common sense to hard science.
Interest in the patient's views of his or her illness and treatment has increased dramatically. However, our ability to appropriately measure such issues lags far behind the level of interest and need. Too often such measurement is considered to be a simple and trivial activity that merely requires the application of common sense. However, good quality measurement of patient-reported outcomes is a complex activity requiring considerable expertise and experience. This review considers the most important issues related to such measurement in the context of chronic disease and details how instruments should be developed, validated and adapted for use in additional languages. While there is often consensus on how best to undertake these activities, there is generally little evidence to support such accord. The present article questions these orthodox views and suggests alternative approaches that have been shown to be effective.


News in diabetology 2022.
The use of new antidiabetic drugs in clinical practice in the last two decades has completely changed the Type 2 diabetes management. Following the results of new clinical trials, international recommendations for the treatment of diabetes were regularly modified. In the field of Type 1 diabetes, new technologies have appeared, such as smart insulin pens. We can await once weekly insulins and dual GLP-1 and GIP analogues in the near future.


Influence of adult role modeling on child/adolescent helmet use in recreational sledging: an observational study.
During recreational sledging (tobogganing), the head represents the most frequent injured body region with approximately one-third of all sledging injuries among children and adolescents. Whether children are wearing a helmet or not might be influenced on parental encouragement and role modeling of helmet use. Therefore, the aim of this study was to evaluate the impact of adult helmet use on child/adolescent helmet use in recreational sledging. More than 500 adults sitting together with another adult or child/adolescent on a two-seater sledge were interviewed during two winter seasons at the bottom of six sledging tracks on demographics, mean frequency of sledging per season, self-estimated skill level, risk-taking behavior, and the use of a helmet. Total helmet use of all observed persons was 41.0 %. Helmet use among interviewed adults significantly increased with increasing age up to 45 years, frequency of sledging, and skill level, respectively. Helmet use of interviewed adults was 46.5 % if a child/adolescent was sitting on the same sledge and 29.8 % (odds ratios (OR): 2.1, 95 % confidence intervals (CI): 1.4-2.9, p < 0.001) when sledging together with another adult. Helmet use was 71.3 % among children/adolescents and 26.7 % among adults (OR: 6.8, 95 % CI: 4.6-10.1, p < 0.001) sitting on the same sledge as the interviewed person, respectively. Adults were wearing more often a helmet during recreational sledging when sitting together with a child/adolescent on the sledge. However, helmet use during sledging is clearly below 50 %. Thus, more intense educational campaigns on helmet use are urgently needed for tobogganists.


The MRCGP Clinical Skills Assessment: an integrative review of evidence.
Background Successful completion of all three components of the Membership of the Royal College of General Practitioners UK (MRCGP) is required for a doctor to practise independently as a general practitioner (GP). One component, the Clinical Skills Assessment (CSA), is a high fidelity, high stakes examination designed to provide an objective external assessment of clinical skills. Aim The aim of this integrative review was to identify, critically appraise and synthesise published empirical evidence on the CSA to identify areas for further inquiry or future collaboration. Design and setting An integrative review of empirical literature focused on the MRCGP CSA. Method A search strategy was developed to conduct an integrative review of empirical published literature. The quality of studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Results 11 of the 31 records reviewed were included. Studies were heterogeneous looking at the use of simulated patients, child actors and mock CSAs. Variables contributing to performance on the CSA, with a particular emphasis on the International Medical Graduate, were identified. Conclusion A small pool of published evidence regarding the CSA exists, focused on factors influencing CSA performance. Future research could explore the effectiveness of interventions to improve performance on the CSA and use robust measures to consider candidates' experience of the CSA.


High magnetoelectric coupling of Metglas and P(VDF-TrFE) laminates.
Magnetoelectric (magnetic/piezoelectric) heterostructures bring new functionalities to develop novel transducer devices such as (wireless) sensors or energy harvesters and thus have been attracting research interest in the last years. We have studied the magnetoelectric coupling between Metglas films (2826 MB) and poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) in a laminate structure. The metallic Metglas film itself served as bottom electrode and as top electrode we used an electrically conductive polymer, poly(3,4-ethylene-dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS). Besides a direct electrical wiring via a graphite ink, a novel contactless readout method is presented using a capacitive coupling between the PEDOT:PSS layer and an electrode not in contact with the PEDOT:PSS layer. From the experimental result we determined a magnetoelectric coupling of 1445 V/(cm·Oe) at the magnetoelastic resonance of the structure, which is among the highest reported values for laminate structures of a magnetostrictive and a piezoelectric polymer layer. With the noncontact readout method, a magnetoelectric coupling of about 950 V/(cm·Oe) could be achieved, which surpasses previously reported values for the case of direct sample contacting. 2D laser Doppler vibrometer measurements in combination with FE simulations were applied to reveal the complex vibration pattern resulting in the strong resonant response.


Image analysis and diagnostic classification of hepatocellular carcinoma using neural networks and multivariate discriminant functions.
Hepatocellular carcinoma (HCC) is often difficult to diagnose in cytologic material and small tissue biopsies since histomorphologic information is minimal or absent. The potential for misdiagnosis is greatest in attempting to discriminate well-differentiated HCC from dysplastic hepatocytes in cirrhosis. We investigated the feasibility of developing artificial intelligence classification methods based on nuclear image analysis data for use as adjuncts to the morphologic diagnosis of HCC. Ninety hematoxylin-eosin stained histologic slides including 56 with well- to poorly differentiated HCC and 34 showing a morphologic continuum from normal to markedly dysplastic benign hepatocytes were assembled from four laboratories. A relatively inexpensive PC-based image analysis system was used to measure 35 nuclear morphometric and densitometric parameters of 100 nuclei in each specimen. The data were randomized into classification training and testing sets containing equal numbers of benign and HCC samples. Objective diagnostic classification criteria for HCC based on neural networks and multivariate discriminant functions (DFs) were developed for the most discriminatory subsets of morphometric, densitometric, and combined morphometric/densitometric variables as selected by stepwise discriminant analysis of training data. Morphometric parameters provided the best results with the following testing data positive and negative predictive values (PV+ and PV-) for HCC classification: 86.2% PV+ and 81.3% PV- for a linear DF, 85.7% PV+ and 76.5% PV- for a quadratic DF and 100% PV+ and 85.0% PV- for a neural network. Our results demonstrate that nuclear image analysis-based objective classification criteria for HCC can be developed using artificial intelligence methods and that histologic material prepared at different institutions can be reliably classified. Neural networks for HCC classification were superior to linear and quadratic DFs. Morphometric data yielded the best results compared with densitometric or combined morphometric/densitometric data.


A uniform stable P-type graphene doping method with a gold etching process.
Graphene is one of the materials with the most potential for post-silicon electronics because of its outstanding electrical, optical, and mechanical properties. However, the lack of a uniform stable doping method extremely limits the various possible applications of graphene. Here, we developed a uniform and stable graphene efficient p-doping method. Through etching a thin gold film on graphene with a KI/I2 solution, iodine complexes are produced as the dopant absorbing on the graphene surface, and induce extra holes in graphene. Utilizing this method, the graphene film can be effectively doped to p-type without producing undesirable defects, and the roughness of the graphene surface can still be maintained at an ultra-low nanoscale (RMS roughness ∼0.739 nm). The doping effectiveness can be clearly verified by the changes in the Raman spectrum, and the Dirac point shift of the graphene-based transistor, and the reduction of sheet resistance (∼27.2%). Furthermore, the substantially coincident transfer curves after 45 days reveal the long-term stable doping effects. Therefore, this doping method can exploit a way for various graphene-based applications, such as phototransistors, sensors, and organic thin-film transistors.


New benzimidazole derivatives with potential cytotoxic activity--study of their stability by RP-HPLC.
Obtained benzimidazole derivatives, our next synthesized heterocyclic compounds, belong to a new group of chemical bondings with potential anticancer properties (Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2006, J Liguid Chrom Rel Tech 29: 2367-2385; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2008, Wiad Chem 62: 11-12, in Polish; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2011, J Liguid Chrom Rel Tech 34: 1901-1912). We used HPLC analysis to determine stability of these compounds in 0.2% DMSO (dimethyl sulfoxide). Optimisation of the chromatographic system and validation of the established analytical method were performed. Reversed phases (RP-18) and a 1:1 mixture of acetate buffer (pH 4.5) and acetonitrile as a mobile phase were used for all the analysed compounds at a flow rate 1.0 mL/min. The eluted compounds were monitored using a UV detector, the wavelength was specific for compounds 6 and 9 and compounds 7 and 10. The retention time was specific for all four compounds. The used method was found to have linearity in the concentration range of (0.1 mg/mL-0.1 μg/mL) with a correlation coefficient not less than r(2)=0.9995. Statistical validation of the method proved it to be a simple, highly precise and accurate way to determine the stability of benzimidazole derivatives in 0.2% DMSO. The recoveries of all four compounds examined were in the range 99.24-100.00%. The developed HPLC analysis revealed that the compounds studied remain homogeneous in 0.2% DMSO for up to 96 h and that the analysed N-oxide benzimidazole derivatives do not disintegrate into their analogues - benzimidazole derivatives. Compounds 8, 6 and 9 exhibit the best cytotoxic properties under normoxic conditions when tested against cells of human malignant melanoma WM 115.


Eigenfunction analysis of stochastic backscatter for characterization of acoustic aberration in medical ultrasound imaging.
Presented here is a characterization of aberration in medical ultrasound imaging. The characterization is optimal in the sense of maximizing the expected energy in a modified beamformer output of the received acoustic backscatter. Aberration correction based on this characterization takes the form of an aberration correction filter. The situation considered is frequently found in applications when imaging organs through a body wall: aberration is introduced in a layer close to the transducer, and acoustic backscatter from a scattering region behind the body wall is measured at the transducer surface. The scattering region consists of scatterers randomly distributed with very short correlation length compared to the acoustic wavelength of the transmit pulse. The scatterer distribution is therefore assumed to be delta correlated. This paper shows how maximizing the expected energy in a modified beamformer output signal naturally leads to eigenfunctions of a Fredholm integral operator, where the associated kernel function is a spatial correlation function of the received stochastic signal. Aberration characterization and aberration correction are presented for simulated data constructed to mimic aberration introduced by the abdominal wall. The results compare well with what is obtainable using data from a simulated point source.


Optimisation and Benchmarking of Targeted Amplicon Sequencing for Mycobiome Analysis of Respiratory Specimens.
(1) Background: Firm consensus has yet to be established in relation to taxonomic classification and primer choice in targeted amplicon sequencing of the mycobiome. While the nuclear ribosomal internal transcribed spacer (ITS) region are recognized as the formal fungal taxonomic barcode, appraisal of different ITS sub-regions and the influence of DNA extraction methods have not been comprehensively undertaken using human respiratory specimens. (2) Methods: We performed ITS analysis of respiratory (sputum) samples by assessing (a) the effect of alternate DNA extraction techniques and (b) an evaluation of four different ITS primer pairs (ITS1F and ITS2; ITS1-30F and ITS1-217R; gITS7ngs and ITS4ng; and Fseq and Rseq) on the mycobiome profiles generated for mock fungal communities and their respective clinical (airway) specimens. (3) Results: Primer pairs varied in their resulting ITS mycobiome profiles, suggesting that particular pairs may be more relevant for analysis of respiratory samples compared to others. Assessment of DNA extraction methods highlighted lower final DNA concentrations achieved by mechanical disruption compared to enzymatic lysis. However, despite lower yields, DNA liberated by mechanical lysis more readily yielded ITS bands with highest success in combination with the Fseq and Rseq primers. (4) Conclusion: Choice of extraction method, primers used, and sequencing approach are all important considerations in sequencing the mycobiome and should be tailored to sample type. A standardization of approach to mycobiome studies using respiratory specimens will permit more reliable comparisons between studies and improve our understanding of the role of fungi in the human airway.


A Case of Primary Systemic Amyloidosis Involving the Sinonasal Tract.
We present a case of primary systemic amyloidosis diagnosed by endoscopic sinus surgery. A 75-year-old woman had blurred vision in her left eye; computed tomography and magnetic resonance imaging showed shadows of the bilateral paranasal sinuses. Endoscopic sinus surgery was performed, and amyloidosis was diagnosed by histopathology. She had previously been diagnosed with amyloidosis of the stomach, and therefore, she was diagnosed with primary systemic amyloidosis. A systemic workup for additional amyloid deposits revealed no evidence of other diseases. The patient remained under follow-up without further treatment, as no further amyloid deposition or progression of the lesions was seen. Amyloidosis is a rare condition characterized by the deposition of abnormal protein filaments in the extracellular tissue. Generally, systemic amyloidosis does not involve the head and neck region, and the presence of amyloid in the nasal and paranasal sinus mucosa is more likely to be indicative of a localized process. However, in our patient, the lesions were located in both the sinonasal tract and the stomach, indicating systemic amyloidosis. To our knowledge, there have been no previous reports of systemic amyloidosis involving the sinonasal tract, and therefore, we consider this case to be extremely rare.


Contemporary Management of Thyroid Nodules.
Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance.


The ethics of funding embryonic stem cell research: a Catholic viewpoint.
Stem cell research that requires the destruction of human embryos is incompatible with Catholic moral principles, and with any ethic that gives serious weight to the moral status of the human embryo. Moreover, because there are promising and morally acceptable alternative approaches to the repair and regeneration of human tissues, and because treatments that rely on destruction of human embryos would be morally offensive to many patients, embryonic stem cell research may play a far less significant role in medical progress than proponents believe.


Reversal of bilateral rosette cataracts with glycemic control.
This case describes a diabetic with blood glucose levels in the 400s for 3 weeks with severe loss of visual acuity over the past 2 weeks. The exam showed only feather-shaped opacities in her lens, consistent with a cataract. With insulin and fluids alone, her visual acuity dramatically improved and her cataract reversed within 2 weeks. Glycemic control is effective and preferred to surgical intervention for acute hyperglycemia-induced cataracts.


Patterning ITO by Template-Assisted Colloidal-Lithography for Enhancing Power Conversion Efficiency in Organic Photovoltaic.
Highly structured interfaces are very desirable in organic photovoltaic solar cells (OPVs), in order to enhance power conversion efficiency (PCE) by decreasing of the transport path for excited charge carriers in the absorber and increasing the optical path length for photon absorption. Many complicated, high-cost lithographic methods have been attempted to modify the surface of the absorber or substrate. However, solution-based colloidal-lithography processes are scalable and cost-effective, but generally result in non-uniform structured surfaces. In this report, we demonstrated an optimized silica-templated colloidal lithographical approach to create a well-defined and controlled transparent ITO layer for enhancing power conversion efficiency (PCE). Additionally, morphological effects of the patterned ITO on optical properties and PCE were analyzed in detail.