Corrosion Resistance and Thermal Conductivity Enhancement of Reduced Graphene Oxide-BaSO4-Epoxy Composites.
The results of studies on the corrosion protectiveness and thermal conductivity of reduced graphene oxide-BaSO4 epoxy composites are reported here. A commercial epoxy resin and reduced graphene oxide (rGO) were blended with a hardening reagent and then mixed with prepared BaSO4-epoxy resin (B-epoxy). The reduced graphene oxide-BaSO4-epoxy composite (rGO-B-epoxy) paste was used to coat the surfaces of Al 7205 alloy and the corrosion and thermal properties were investigated. A corrosion test in a 3.5 wt% synthetic sea water solution showed that the composite coating containing BaSO4 had the best corrosion resistance. Moreover, the rGO-B-epoxy composite showed better protection against corrosion than the epoxy alone. The rGO-B-epoxy composite with 5 wt% BaSO4 had an in-plane coefficient of thermal conductivity of approximately 165.0 W/m K, and the in-plane thermal diffusivity was 71.38 mm2/s. In standard thermal conductivity tests, all three samples had values below 40 W/m K. The rGO-B-epoxy composites showed good surface corrosion protection and in-plane thermal conductivity.


[Comparative assessment of the efficacy of selective and discrete plasmapheresis in combined preoperative preparation of patients with diffuse toxic goiter].
The paper is concerned with comparative assessment of two methods of plasmapheresis (discrete and selective), employed for preoperative preparation of patients with a severe type of thyrotoxicosis. Selective plasmapheresis by its effect on immunity indices, hormonal status, central hemodynamics and clinical symptomatology was shown to be no inferior to the discrete method. At the same time selective plasmapheresis was not accompanied by allergic reactions, excluding the danger of infection and making preoperative preparation cheaper.


Potentiation of thyroxine 5-deiodination by aminotriazole.
Aminotriazole, a goitrogen, in addition to its known inhibitory effects on the thyroid, demonstrated a unique effect on peripheral deiodination of thyroxine (T4). In contrast to the well-known peripheral effects of goitrogens such as propylthiouracil in inhibiting 5'-deiodinase activity, i.e., to effect a decrease in T4 to triiodothyronine (T3) conversion, aminotriazole had no effect on the 5'-deiodinative pathway. Rather, this goitrogen appeared to stimulate the alternative pathway, viz. T4 5-deiodination, resulting in an increased reverse triiodothyronine (rT3) serum concentration. This was shown in comparisons of serum T4, T3 and rT3 concentrations and serum T3/T4 and rT3/T4 ratios between rats treated with aminotriazole and T4, and rats treated with T4 alone. The finding that aminotriazole may specifically enhance T4 5-deiodination, independently of T4 5'-deiodination, is novel, as this has not been observed in the case of other goitrogens. It is of interest that this goitrogen is devoid of sulphur, which is a prominent constituent of thiourylene compounds which have been noted to affect 5'-deiodination. The potentiating effect of aminotriazole on 5-deiodination of T4 was not attributable to dietary factors.


Metformin therapy in women with polycystic ovary syndrome.
To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters. 50 Indian women with PCOS, 25 unmarried and 25 married, infertile women, were enrolled in this prospective clinical study. After a baseline workup, including body mass index (BMI), waist hip ratio (WHR), Ferriman Gallwey hirsutism scoring, menstrual pattern, levels of fasting insulin, lipids, oral glucose tolerance test (OGTT), serum gonadotropins, estradiol (E2), testosterone, androstenedione, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEAS), patients were given 1000 gm of metformin for 6 months and then reevaluated. In 41 of 50 women who completed treatment, significant improvement in BMI, WHR, menstrual cyclicity (80.5%), ovulation rate (66%), and pregnancy rate (28%) was noted. Statistically significant decrease in lutenising hormone (LH) and LH/FSH ratio with an increase in follicle stimulating hormone (FSH) levels were seen. Levels of high-density lipoprotein (HDL) cholesterol (Chol) increased along with a decrease in total cholesterol. Improvement was noted in ovarian volume, stromal thickness, and number of follicles. There was no change in hirsutism, acne, levels of other sex steroid hormones, and lipids. A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS.


The use of post-mortem computed tomography in the investigation of intentional neonatal upper airway obstruction: an illustrated case.
We present a single case report illustrating the diagnostic role of multi-slice computed tomography (MSCT) in the investigation of suspicious child death where mechanical asphyxia is suspected. The case illustrates how radiological findings that may not be observable on conventional plain X-ray were identified by post-mortem MSCT. We illustrate how MSCT can illustrate the position of a foreign body within the upper airway of a neonate without the need for in situ dissection and how the combination of post-mortem MSCT with skeletal survey can provide enhanced diagnostic information in the investigation of not only whether the child was liveborn but also the consideration as to whether or not death has been caused by upper airway obstruction.


A scoping review of the use of exercise-based upper extremity injury prevention programs for industrial workers.
This study is a scoping review. Exercise-based upper extremity injury prevention programs are used by employers to reduce the cost of work-related injuries in the industrial work setting. The purpose of the study was to identify, report, and evaluate all published literature that describes exercise-based upper extremity injury prevention programs used with an industrial workforce. A systematic search of Medline, ProQuest, Pubmed, and Worldcat databases was performed. Data extracted included the type of outcome tool used, the outcome that was measured, the components of the exercise program, and the effectiveness toward reducing injury. 14 studies were included in the final analysis and summary. 12 articles included strengthening (85%) 10 included stretching (71%), 2 included health coaching (14%), and 2 included work simulation (14%). The most prevalent treatment approach was combined stretching and strengthening which accounted for 5 of the 14 studies, or 36%. The intervention period ranged from 4 weeks to 1 year and the program frequency ranged from before every work shift to weekly performance. There were 22 different outcome measures with health condition reported in 12 of 14 studies (86%) and function reported in 7 of 14 studies (50%). Although many of the studies showed positive benefits to the exercise program, there is a wide variance in the current literature regarding the implementation, supervision, and exercise components of an upper extremity injury prevention program in an industrial work setting. Because there is no commonly-accepted exercise program, a conclusion regarding effectiveness cannot be generalized outside of the environment, supervision requirements, frequency, and duration in which the research was performed. There is a need for improved reporting techniques and a preferred program to be replicated across multiple work settings in order to allow generalizability of findings.


Loss of sigma-factor of RNA polymerase of Xanthomonas campestris pv. oryzae during phage Xp10 infection.
Ten min after infection of Xanthomonas campestris pv. oryzae by phage Xp10, a sharp decrease in the activity of the host RNA polymerase was observed. Host RNA polymerase from phage-infected and uninfected cells was purified, and their properties were compared. The enzyme from uninfected cells contained four polypeptides with Mr = 155,000, 155,000, 93,000, and 37,000, respectively, and assembled with a stoichiometry of alpha 2 beta beta' sigma. The enzyme from infected cells lacked the sigma-subunit. The enzyme from uninfected cells utilized Xp10 DNA and poly[d(A-T)] as templates, the enzyme from phage-infected cells failed to transcribe Xp10 DNA, but retained the ability to transcribe poly(A-T). The regions of the Xp10 genome transcribed by the two enzymes were also investigated. The enzyme from uninfected cells transcribed the leftmost 25-30% of the Xp10 genome. The enzyme from phage-infected cells also transcribed the same region, but the enzyme activity was very low. Other properties such as (a) the response to RNA polymerase inhibitors, (b) the effect of N-ethylmaleimide, (c) the requirement of Mg2+ and Mn2+, and (d) the optimum temperature and pH of the two enzymes were very similar.


Cycloidal CT with CNN-based sinogram completion and in-scan generation of training data.
In x-ray computed tomography (CT), the achievable image resolution is typically limited by several pre-fixed characteristics of the x-ray source and detector. Structuring the x-ray beam using a mask with alternating opaque and transmitting septa can overcome this limit. However, the use of a mask imposes an undersampling problem: to obtain complete datasets, significant lateral sample stepping is needed in addition to the sample rotation, resulting in high x-ray doses and long acquisition times. Cycloidal CT, an alternative scanning scheme by which the sample is rotated and translated simultaneously, can provide high aperture-driven resolution without sample stepping, resulting in a lower radiation dose and faster scans. However, cycloidal sinograms are incomplete and must be restored before tomographic images can be computed. In this work, we demonstrate that high-quality images can be reconstructed by applying the recently proposed Mixed Scale Dense (MS-D) convolutional neural network (CNN) to this task. We also propose a novel training approach by which training data are acquired as part of each scan, thus removing the need for large sets of pre-existing reference data, the acquisition of which is often not practicable or possible. We present results for both simulated datasets and real-world data, showing that the combination of cycloidal CT and machine learning-based data recovery can lead to accurate high-resolution images at a limited dose.


Cardiac Manifestations of Multisystem Inflammatory Syndrome in Children (MIS-C) Following COVID-19.
To review the spectrum of cardiac manifestations and treatments of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Studies demonstrate that up to 80% of children with MIS-C may have cardiac involvement on a spectrum of severity. Cardiac manifestations include myocarditis, coronary artery aneurysms, conduction abnormalities, and arrhythmias. Current treatments, including inotropic support, immunomodulatory therapy, and anti-coagulation, have been effective at resolving these cardiac findings in the majority of patients. COVID-19 can also cause myocarditis in the acute stage of illness and recent descriptions of COVID-19 vaccine myocarditis have occurred. Cardiac manifestations are common in MIS-C and should be assessed for at presentation and during the clinical course as indicated.


Glutamatergic Signaling a Therapeutic Vulnerability in Melanoma.
Like other cancers, melanomas are associated with the hyperactivation of two major cell signaling cascades, the MAPK and PI3K/AKT pathways. Both pathways are activated by numerous genes implicated in the development and progression of melanomas such as mutated BRAF, RAS, and NF1. Our lab was the first to identify yet another driver of melanoma, Metabotropic Glutamate Receptor 1 (protein: mGluR1, mouse gene: Grm1, human gene: GRM1), upstream of the MAPK and PI3K/AKT pathways. Binding of glutamate, the natural ligand of mGluR1, activates MAPK and PI3K/AKT pathways and sets in motion the deregulated cellular responses in cell growth, cell survival, and cell metastasis. In this review, we will assess the proposed modes of action that mediate the oncogenic properties of mGluR1 in melanoma and possible application of anti-glutamatergic signaling modulator(s) as therapeutic strategy for the treatment of melanomas.


Estimation of the density of sodium entry sites in frog skin epithelium from the uptake of [3H]benzamil.
1. The inhibition of short circuit current in frog skin by benzamil (N-benzyl-amidino-3,5-diamino-6-chloropyrazine carboxamide) was investigated. When skins were bathed on both sides by Ringer solution (pH 7.6) the affinity was 5 x 10(7) M-1. When the sodium concentration was reduced to 1.1 mM and the pH adjusted to 6.5 the affinity increased to 8.5 x 10(8) M-1. 2. A method is described for measuring uptake of [3H]benzamil into the mucosal (outer) surface of pieces of isolated epithelium, 0.95 cm2 in area, under open circuit conditions. 3. The relation of [3H]benzamil uptake at the mucosal surface to its concentration was measured in solutions containing 1.1 mM-sodium and adjusted to pH 6.5. Uptake could be resolved into a linear component (10.2 f-mole nM-1) and a saturable component (21.5 f-mole cm-2) with a half saturating concentration of 1 nM. 4. In the presence of amiloride (1 microM) or unlabelled benzamil (1 microM) uptake was linear with concentration, and was, respectively, 9.2 f-mole nM-1 and 8.8 f-mole nM-1. When the pH was reduced to 3.5 uptake was again linear but reduced to 3.3 f-mole nM-1. 5. The identity of the saturable component of [3H]benzamil uptake to sodium entry sites is discussed. The results suggest a sodium entry site density of around 130 micron-2 of mucosal surface.


Improved resolution in two-dimensional 1H NMR spectra of peptides by band-selective, homonuclear decoupling during both the evolution and acquisition periods: application to characterization of the binding of peptides by heparin.
Two-dimensional 1H NMR experiments that achieve band-selective, homonuclear decoupling in both the indirectly detected F1 and directly detected F2 dimensions were used to assign the highly overlapped 1H NMR spectrum of the peptide Ac-SRGKARVRAKVKDQTK-NH2, both free in solution and bound to heparin. Band-selective, homonuclear decoupling during the evolution period was achieved using a double pulsed field gradient spin-echo (DPFGSE) with semi-selective shaped pulses; band-selective, homonuclear decoupling during the acquisition period was achieved by time-shared semi-selective shaped pulse decoupling. Regular TOCSY, ROESY and NOESY spectra and TOCSY, ROESY and NOESY spectra measured with band-selective, homonuclear decoupling in the evolution (F1) dimension (BASHD-TOCSY, ROESY and NOESY spectra) and with band-selective, homonuclear decoupling in both the F1 and F2 dimensions (D-(or Double)-BASHD-TOCSY, ROESY and NOESY spectra) are reported and compared for the peptide and its heparin complex. Complete assignment of the 1H-NMR spectra of the free and heparin-complexed peptide was achieved with the high resolution of the D-BASHD-TOCSY, ROESY and NOESY spectra. Characterization of the heparin-complexed peptide is of interest because of the ability of the peptide to neutralize the anticoagulant activity of heparin.


Inositol phosphosphingolipid phospholipase C1 regulates plasma membrane ATPase (Pma1) stability in Cryptococcus neoformans.
Cryptococcus neoformans is a facultative intracellular pathogen, which can replicate in the acidic environment inside phagolysosomes. Deletion of the enzyme inositol-phosphosphingolipid-phospholipase-C (Isc1) makes C. neoformans hypersensitive to acidic pH likely by inhibiting the function of the proton pump, plasma membrane ATPase (Pma1). In this work, we examined the role of Isc1 on Pma1 transport and oligomerization. Our studies showed that Isc1 deletion did not affect Pma1 synthesis or transport, but significantly inhibited Pma1 oligomerization. Interestingly, Pma1 oligomerization could be restored by supplementing the medium with phytoceramide. These results offer insight into the mechanism of intracellular survival of C. neoformans.


What happens when nothing happens? An investigation of pauses as a compensatory mechanism in early Alzheimer's disease.
Lexical-semantic impairment is one of the earliest symptoms of Alzheimer's disease (AD) and is usually examined by single word processing tasks. During speech production, pauses are often investigated as a hallmark of a patient's lexical-semantic decline. In the current study, we put forward the hypothesis that pauses reflect different processes according to the type of discourse. We believe that lexical and semantic impairment would predict a patient's pause frequency in a picture-based narrative (PBN) while anterograde memory would predict a patient's pause frequency in a memory-based narrative (MBN). To demonstrate this, we recruited 17 early AD patients and 17 matched controls. They underwent a full neuropsychological and language assessment and two narrative production assessments. We compared pause duration and frequency in the AD participants' and healthy controls' PBN and MBN. A multiple regression model was used in each narrative and in each group individually to assess the relationship between cognitive processes and pause frequency. Our results show that participants with AD produced more pauses in the PBN only. The frequency was predicted by semantic fluency performance with which it was positively correlated, contrary to what was expected. In the MBN, pause frequency in the AD participants was positively correlated with and predicted by their memory performance. We then examined the neuroanatomical correlates of pause frequency in the AD participants. Considering the PBN, pause frequency was also positively correlated with the grey matter density of the anterior temporal lobe. These findings suggest that patients use pauses as compensatory mechanisms in the earliest stages of AD. Pauses therefore may reflect the time required for the compensation and the realisation of a weak process depending on the narrative task and should be considered as a positive sign.


Ca2+-dependent membrane bound protein fraction from rabbit gastric mucosa contains a protein whose histidyl residue is phosphorylated.
We found an autophosphorylated protein with a molecular weight of 40 kDa (p40) in the crude annexin fraction of rabbit gastric mucosa, i.e., the materials released by EGTA from the membrane fraction obtained in the presence of Ca2+. This protein was enriched in chief cells in the gastric glands, and also found in the heart and the liver by Western blotting. The protein bound to phenyl-Sepharose in the presence of Ca2+ and showed extremely basic nature. The phosphorylation site of p40 was considered to be histidyl residue based on the stability to the various agents, the synthesizing activity of ATP from ADP, and the results of phosphoamino acid analysis. The autophosphorylation of p40 was augmented several tenth fold by GDP, Ras, myelin basic protein, or H1 histone at micromolar range. The phosphorylated form was rapidly dephosphorylated in the presence of cold ATP, succinate, and CoA, suggesting that p40 has succinyl-CoA synthetase activity. In fact, a peptide fragment from p40 showed a striking homology with the alpha subunits of succinyl-CoA synthetases from Escherichia coli, Dictyostelium discoideum, and rat liver. These results suggest that p40 is extramitochondrial alpha subunit of succinyl-CoA synthetase or its homologue.


Incidence of new pulmonary perfusion defects after routine cardiac catheterization.
The incidence of pulmonary perfusion defects after routine cardiac catheterization was assessed in 57 patients by comparing ventilation-perfusion lung scans obtained before and 1 day after catheterization. Patients were prospectively randomized to two groups, one in which right heart catheterization was performed using an antecubital venous cutdown procedure and one in which the percutaneous femoral vein approach was used. Seven patients (12 percent) had new postcatheterization perfusion defects consistent with pulmonary emboli. These patients did not differ significantly from patients without new defects in clinical characteristics, duration of catheterization, hemodynamic variables or route of right heart catheterization. The data suggest that pulmonary embolism may be a more common complication of routine cardiac catheterization than previously appreciated.


Suicidal urges and attempted suicide at multiple time scales in borderline personality disorder.
There is strong evidence for an enduring suicidal diathesis among individuals with a history of suicide attempts, particularly among people diagnosed with borderline personality disorder (BPD). However, the progression of suicidal crises among people predisposed to suicidal behavior remains poorly understood. Via multilevel structural equation modeling we tested the hypothesis that a history of attempted suicide predicts a stronger dynamic link between affect and impulsivity with suicidal ideation (i.e., suicidal urges) - both moment-to-moment and day-to-day. 153 patients diagnosed with BPD, 105 of whom had a history of medically serious suicide attempts completed a 21-day ecological momentary assessment protocol (17,926 total assessments). Individuals with higher average levels of negative affect reported more suicidal thoughts. Moments characterized by more negative affect, hostility, impulsivity, and less positive affect were also characterized by elevated suicidal ideation. For hostility and positive affect, these significant links generalized to the daily level. At the same time, for negative affect and hostility the within-person coupling was stronger among attempters in comparison to non-attempters, and these effects did not significantly differ across timescales. Follow-up studies replicating our findings of the dysregulation-suicidality nexus in clinically more diverse samples are needed. The diathesis for suicidal behavior manifests in tighter dynamic links between negative affect or hostility and suicidal ideation. Because these within-person links were amplified in attempters compared to non-attempters, differential coupling patterns may index potentially lethal processes that generalize beyond BPD reflecting distinct diathesis components.


Effects of poor bone window on the assessment of cerebral autoregulation with transcranial Doppler sonography - a source of systematic bias and strategies to avoid it.
The consequences of poor insonation conditions on autoregulation parameters assessed with transcranial Doppler (TCD) are unclear. We present two new complementary methods to assess the quality of a TCD signal. Inserting a thin aluminium foil between TCD probe and skin makes a simple model to artificially worsen a good insonation window. Validation studies are presented. We assessed insonation quality and cerebral autoregulation parameters with transfer function analysis and cross correlation in 46 healthy volunteers with and without the aluminium foil model. The same studies were operated on 45 patients with good insonation windows, naïve, after worsening the bone window and during constant infusion of an ultrasound contrast agent. For studying reproducibility, we assessed autoregulation twice in 30 patients with poor bone windows, with and without constant contrast infusion. Both methods to measure insonation quality are valid and reproducible. The aluminium foil model realistically simulates a natural poor bone window, reducing the signal quality (e.g. energy of the signal spectrum from 33.4+/-3.5 to 26.2+/-2.5 dB, p<0.001). Thereby, the autoregulation parameters are systematically biased (e.g. phase difference from 37.3+/-10.1 degrees to 25.9+/-15.1 degrees , p<0.001); while with the use of an ultrasound contrast agent this can be largely compensated (phase difference 35.7+/-10.7 degrees , p<0.001). The reproducibility is significantly improved (ICC from 0.76 to 0.90, p<0.05). Poor bone windows can cause considerable bias in TCD autoregulation parameters. This bias might be avoided by the use of ultrasound contrast agents, which may greatly improve the credibility of TCD autoregulation assessment in elderly patients.


Isolation of novel isoforms of estrogen receptor genes from Xenopus gonad and brain.
We isolated four variants of ER alpha mRNA, two each from the brain and gonad of the Xenopus embryo (brain, bER alpha 1 and bER alpha 2; gonad, gER alpha 1 and gER alpha 2). The N-terminal-domain of ER alpha differed between the brain and gonad. While the C-terminal region downstream of the DNA-binding domain of ER alpha differed between ER alpha 1 and ER alpha 2 in both the brain and gonad, each of ER alpha 1 and ER alpha 2 contained the same sequence sets (bER alpha 1 and gER alpha 1; bER alpha 2 and gER alpha 2) between the brain and gonad. Both bER alpha 1 and gER alpha 1 contained the same full-length, C-terminal estrogen receptor, whereas the C terminus of bER alpha 2 and gER alpha 2 lacked half of the DNA-binding, ligand-binding, and transcriptional activation domain. Although gER alpha was mainly expressed in the gonad, both bER alpha and gER alpha were expressed in the brain of the Xenopus embryo at stage 50. These isoforms might be transcribed by alterative splicing of a single gene. Two gonad ER beta s differing in the length of the N-terminal sequence were isolated from the Xenopus gonad. While ER beta was expressed in the gonad, it was not expressed in the brain of the Xenopus embryo at stage 50.


How Patient Education Influences Utilization of Nonpharmacological Modalities for Persistent Pain Management: An Integrative Review.
Opioid analgesic misuse and abuse has given rise to an epidemic that has added to an increase in opioid-related overdoses and deaths. Adults with persistent noncancer pain (PNCP) are primarily treated with opioid analgesics. Many remain on these medications long term. Most of these patients are unaware of other effective measures for managing PNCP, such as nonpharmacologic modalities (NPMs). This lack of familiarity with NPMs presents a key contributor to the problem of NPM underuse among adult PNCP patients. This integrative review sought to identify key factors that contribute to NPMs underuse and the effect of education on patients' adoption or use for PNCP management. Integrative review. A literature search was conducted using PubMed, CINAHL, Embase, Cochrane, and hand-searching of the literature published between 2002 and November 2017. Systematic screening using the Johns Hopkins Nursing evidence appraisal tools yielded articles that were analyzed and synthesized to identify themes, and patterns. Nineteen research articles were identified with these main themes: NPMs are effective in PNCP management, lack of familiarity with NPMs influences patients' willingness to try them, and access to local NPMs must be addressed to facilitate use. Findings suggest that patient education about NPMs has the potential to motivate patients to try these modalities, which may increase overall use of NPMs for PCNP. Nurses could play a vital role in ensuring evidence-based NPMs are introduced to PNCP patients, which could increase patients' use of these measures and improve outcomes.


A computational microscope focused on the sense of smell.
In this article, we review studies of the protagonists of the perception of smell focusing on Odorant-Binding Proteins and Olfactory Receptors. We notably put forward studies performed by means of molecular modeling, generally combined with experimental data. Those works clearly emphasize that computational approaches are now a force to reckon with. In the future, they will certainly be more and more used, notably in the framework of a computational microscope meant to observe how the laws of physics govern the biomolecular systems originating our sense of smell.


Association between phase angle and functional disability among patients with lumbar spinal stenosis: The SPSS-OK study.
Whether the lower phase angle associated with worse physical function is a result of pain and muscle weakness in patients with lumbar spinal stenosis (LSS) is unclear. To evaluate the association between phase angle and back pain-specific disabilities in patients with LSS. In this single-center, cross-sectional study, 491 participants with LSS were enrolled. The phase angle and back pain-specific disability were measured using bioelectrical impedance analysis and the Oswestry Disability Index, respectively. General linear models were used to examine associations between phase angle and the Oswestry Disability Index with or without adjustment for age, sex, low back and lower limb pain, numbness in the lower extremities, total fat mass, and lower limb muscle mass. The mean (SD) phase angle was 4.4∘ (1.0∘), and the mean Oswestry Disability Index was 36.1 (14.1) points. Greater phase angles were associated with less Oswestry Disability Index points (p= 0.037) independent of fat mass, low back pain, and hip or lower limb pain. A lower phase angle was associated with worse functional disability. Low phase angle may be an indicator of functional impairment due to low back pain associated with LSS.


Sn2 B5 O9 Cl: A Material with Large Birefringence Enhancement Activated Prepared via Alkaline-Earth-Metal Substitution by Tin.
The excellent birefringent materials are needed for optical systems. Herein, we reported a new compound, the first tin borate chloride, Sn2 B5 O9 Cl (SBOC) with a large birefringence (0.168 at 546 nm) measured by the polarizing microscope. Its birefringence is 16 times that of the isostructural Ba2 B5 O9 Cl (BBOC) compound (0.010@ at 546 nm). The results show that the birefringence enhancement originates mainly from the Sn2+ polyhedra. We propose that the birefringence can be enlarged by substituting the alkaline-earth metal cation by the Sn2+ cation in the isostructural borate with small birefringence. This strategy will guide the discovery of large birefringent materials in the future.


Metabolic labeling and LC-MS/MS-based identification of interleukin-1α-induced secreted proteomes from epithelial cells in the presence or absence of serum.
The unbiased identification of cytokine-induced, secreted proteins from cells cultured in serum-containing medium is challenging. Here, we describe an experimental and bioinformatics workflow to label interleukin-1α-regulated proteins in living cells with the methionine analogue L-homopropargylglycine. We detail their purification and identification by means of CLICK-chemistry-based biotinylation followed by nanoHPLC-MS/MS. A side-by-side comparison of enriched proteins and their ontologies to serum-free conditions demonstrates the sensitivity and specificity of this approach to study the inducible secreted proteomes of epithelial cells.


Meta-analysis of material properties influencing nanoparticle plasma pharmacokinetics.
Thorough characterization of the plasma pharmacokinetics (PK) is a critical step in clinical development of novel therapeutics and is routinely performed for small molecules and biologics. However, there is a paucity of even basic characterization of PK for nanoparticle-based drug delivery systems. This has led to untested generalizations about how nanoparticle properties govern PK. Here, we present a meta-analysis of 100 nanoparticle formulations following IV administration in mice to identify any correlations between four PK parameters derived by non-compartmental analysis (NCA) and four cardinal properties of nanoparticles: PEGylation, zeta potential, size, and material. There was a statistically significant difference between the PK of particles stratified by nanoparticle properties. However, single linear regression between these properties and PK parameters showed poor predictability (r2 < 0.10 for all analyses), while multivariate regressions showed improved predictability (r2 > 0.38, except for t1/2). This suggests that no single nanoparticle property alone is even moderately predictive of PK, while the combination of multiple nanoparticle features does provide moderate predictive power. Improved reporting of nanoparticle properties will enable more accurate comparison between nanoformulations and will enhance our ability to predict in vivo behavior and design optimal nanoparticles.


Effects of Corynebacterium parvum and BCG therapy on immune parameters in patients with disseminated melanoma. A sequential study over 28 days. II. Changes in non-specific (NK, K and T cell) lymphocytoxicity and delayed hypersensitivity skin reactions.
C. parvum and BCG produced significant changes in NK, K and T cell lymphocytotoxicity using a Chang liver target cell. A consistent temporal pattern over 28 days of early depression, recovery, overshoot and then decline was described. This was particularly marked for C. parvum and 'K' cell activity. Skin test reactivity to recall antigens at 28 days was not appreciably different from the pre-immunization reactivity. The importance of using lymphocyte concentration-cytotoxicity titration curves and the linearization of such curves is discussed. An immunotherapy schedule with 3 weekly immunization intervals is proposed as the optimum schedule in patients receiving C. parvum at a dose of 2.0 mg/m2 i.v.


Mechanisms in cochlear hair cell mechano-electrical transduction for acquisition of sound frequency and intensity.
Sound signals are acquired and digitized in the cochlea by the hair cells that further transmit the coded information to the central auditory pathways. Any defect in hair cell function may induce problems in the auditory system and hearing-based brain function. In the past 2 decades, our understanding of auditory transduction has been substantially deepened because of advances in molecular, structural, and functional studies. Results from these experiments can be perfectly embedded in the previously established profile from anatomical, histological, genetic, and biophysical research. This review aims to summarize the progress on the molecular and cellular mechanisms of the mechano-electrical transduction (MET) channel in the cochlear hair cells, which is involved in the acquisition of sound frequency and intensity-the two major parameters of an acoustic cue. We also discuss recent studies on TMC1, the molecule likely to form the MET channel pore.


Relationship of medial arterial calcinosis to autonomic neuropathy and adverse outcomes in a diabetic veteran population.
Medial arterial calcinosis (MAC) is associated with neuropathy, amputation, and mortality through an unknown mechanism. We hypothesized that MAC was a marker of autonomic neuropathy rather than a risk factor and that the outcomes were due to autonomic neuropathy. All subjects in an ongoing prospective study of diabetic foot conditions in a diabetic veteran cohort who received a foot radiograph between 11/7/90 and 11/5/93 were included. Autonomic neuropathy measured as either heart rate variability with timed respiration or postural hypotension. A logistic model predicted the presence of MAC at baseline and Cox proportional models assessed the relative contribution of autonomic neuropathy and traditional risk factors for the outcomes of ulceration, amputation, and death. MAC was identified in 181 subjects, no MAC in 253 subjects, and 39 were excluded due to disagreement between observers. Both measures of autonomic neuropathy were independent predictors of MAC at baseline, even after adjustment for vibration sensation loss in a logistic model. MAC was associated with an increased risk for ulceration (hazards ratio, HR: 2.1, 95% confidence intervals, CI, 1.4-3.1), amputation (HR 3.3, 95% CI 1.5-7.4), and mortality (HR 1.6, 95% CI 1.1-2.2). The addition of either autonomic measure of neuropathy did not change the MAC HR or significantly improved the fit of the model. Our hypothesis that the excess mortality, amputation, and ulceration in persons with MAC could be explained by autonomic neuropathy measured as postural hypotension or heart rate variability with measured respiration was not supported.


Heatwave hit phase shifted coral reefs: Zoantharian mass mortality record.
Phase shift is characterized by an abrupt change in the structure of a community in response to a disturbance that can break its resistance, displacing it from its natural variation. This phenomenon has been recognized in several ecosystems and often points to human activities as the main cause. However, reactions of shifted communities to anthropogenic impacts have been less studied. In recent decades, heatwaves resulting from climate change have strongly affected coral reefs. Mass coral bleaching events are recognized as the main cause of coral reef phase shifts on a global scale. In 2019, an unprecedented heatwave hit the southwest Atlantic Ocean causing mass coral bleaching in non-degraded and phase-shifted reefs of Todos os Santos Bay, at an intensity never recorded in a 34-year historical series. We analyzed the effects of this event on the resistance of phase-shifted reefs, dominated by the zoantharian Palythoa cf. variabilis. Using benthic coverage data from 2003, 2007, 2011, 2017, and 2019, we analyzed three non-degraded reefs and three phase-shifted reefs. We estimated the coverage and bleaching of corals and P. cf. variabilis on each reef. There was a reduction in coral coverage in non-degraded reefs before the 2019 mass bleaching event (i.e., heatwave). However, there was no significant coral coverage variation after the event and the structure of non-degraded reef communities did not change. In phase-shifted reefs the coverage of zoantharians did not change significantly before the 2019 event, however, after the mass bleaching, there was a significant reduction in the coverage of these organisms. Here we revealed that the resistance of the shifted community was broken, and its structure was altered, indicating that reefs in this condition were more susceptible to bleaching disturbance than non-degraded reefs.


Proximal radio-ulnar synostosis treated by interpositional silicone arthroplasty. A case report.
A case of post-traumatic proximal radio-ulnar synostosis in a young adult is described. Treatment was by excision of 1 cm of the shaft just below the synostosis and interposition of a radial head silicone implant. The functional result was excellent after 10 years.


A simple method for estimating activation energies using the fragmentation yield: collision-induced dissociation of iron(II)-phenanthroline complexes in an electrospray ionization mass spectrometer.
The gas-phase stabilities of Fe(Phi)3(2+) complexes, where Phi represents the 1,10-phenanthroline, 5-chloro-1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, and 4,7-diphenyl-1,10-phenanthroline ligands were investigated by collision-induced dissociation (CID) in the capillary-first skimmer region upon changing the voltage difference between the capillary and the skimmer. The loss of only one ligand from the Fe(Phi)3(2+) complexes was observed with each of the phenanthroline ligands studied. An increase in the voltage difference between the capillary and the skimmer resulted in a higher fragmentation yield as calculated from the intensity of the precursor and the fragment ion. The fragmentation yield versus capillary-skimmer voltage difference plots were evaluated by means of the Arrhenius and the Rice-Ramsperger-Kassel (RRK) model by fitting the model parameters to the experimental data. Both models yielded practically the same results. In addition, if the internal energy gained through the capillary-skimmer region is estimated correctly, the approximate value of the critical energy (activation energy) for fragmentation can be extracted from the fragmentation yield versus capillary-skimmer voltage difference plots. It was found that the gas-phase stabilities of the Fe(Phi)3(2+) complexes are nearly identical except for the more stable Fe(II)-4,7-diphenyl-1,10-phenanthroline complex. The critical energy for fragmentation was estimated to be approximately 1.2 and 0.9 eV for the Fe(II)- 4,7-diphenyl-1,10-phenanthroline, and the other complexes, respectively.


The NF-ĸB p50 subunit generated by KPC1-mediated ubiquitination and limited proteasomal processing, suppresses tumor growth.
Nuclear factor-ĸB (NF-ĸB) is an important transcriptional regulator of key cellular processes, including cell cycle, immune response, and malignant transformation. We found that the ubiquitin ligase Kip1 ubiquitination-promoting complex subunit 1 (KPC1; also known as Ring finger protein 123 - RNF123) stimulates ubiquitination and limited proteasomal processing of the p105 NF-ĸB precursor to generate p50, the active subunit of the heterodimeric transcription factor. KPC1 binds to the ankyrin repeats' (AR) domain of NF-ĸB p105 via a short binding site of 7 amino acids-968-WILVRLW-974. Though mature NF-ĸB is overexpressed and constitutively active in different tumors, we found that overexpression of the p50 subunit, exerts a strong tumor suppressive effect. Furthermore, excess of KPC1 that stimulates generation of p50 from the p105 precursor, also results in a similar effect. Analysis of transcripts of glioblastoma and breast tumors revealed that excess of p50 stimulates expression of many NF-ĸB-regulated tumor suppressive genes. Using human xenograft tumor models in different immune compromised mice, we demonstrated that the immune system plays a significant role in the tumor suppressive activity of p50:p50 homodimer stimulating the expression of the pro-inflammatory cytokines CCL3, CCL4, and CCL5 in both cultured cells and in the xenografts. Expression of these cytokines leads to recruitment of macrophages and NK cells, which restrict tumor growth. Finally, p50 inhibits the expression of the programmed cell death-ligand 1 (PDL1), establishing an additional level of a strong tumor suppressive response mediated by the immune system.


Interleukin 1 alpha mRNA in virus-transformed T and B cells.
IL-1 alpha cDNA clone was isolated from a T cell line infected by the human T lymphotropic retrovirus type-I (HTLV-I/ATLV). We found significant amounts of mRNA hybridizing to IL-1 alpha cDNA not only in HTLV-I-transformed T cells but also in Epstein-Barr Virus-transformed B cells. A part of IL-2 receptor inducing activity in Adult T cell leukemia (ATL) cell line seems to be due to IL-1 alpha.


Making research a requirement of treatment: why we should sometimes let doctors pressure patients to participate in research.
When a patient could be offered one of multiple established treatments, doctors should be able to offer treatment only if the patient agrees to participate in research aimed at determining which of the treatments is most effective. Making treatment conditional on research participation will help researchers complete badly needed studies.


3-4 Cycles vs 6 Cycles NACT in Advanced Stage Epithelial Ovarian Cancer: Survival is not Determined by the Number of NACT Cycles.
The aim of this study was to compare the disease-free survival (DFS) and overall survival (OS) of patients who underwent interval cytoreductive surgery after 3-4 cycles or 6 cycles of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer patients. Out of 219 patients with advanced epithelial ovarian cancer,123 patients received 3-4 cycles and 96 patients received 6 cycles of platinum-based NACT. Afterwards, laparotomy was performed for interval cytoreductive surgery. No statistically significant difference was found for DFS and OS of the patients who received 3-4 cycles and those who received 6 cycles of NACT (HR:1.047,95.0%CI [0.779-1.407]; p:0.746 for DFS, and HR:1.181,95.0% CI [0.818-1.707]; p:0.368 for OS). Evaluating 123 patients who received 3-4 cycles of NACT;87 patients (70.7%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS compared to 36 patients(29.3%) with any residual tumor (HR:1.830,95.0% CI [1.194-2.806]; p:0.003 for DFS, and HR:1.946,95.0% CI [1.166-3.250]; p:0.009 for OS).96 patients who received 6 courses of NACT were evaluated;63 patients (65.6%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS than 33 patients (34.4%) with any residual tumor (HR:1.716,95.0% CI [1.092-2.697];p:0.010 for DFS, and HR:1.921,95.0%CI [1.125-3.282]; p:0.013 for OS). In patients with advanced ovarian cancer,there is no significant difference in DFS and OS between 3-4 cycles or 6 cycles of NACT.The most important factor determining survival is whether macroscopic residual tumor tissue remains after interval cytoreductive surgery following NACT.


Hypothermic machine perfusion in liver transplantation.
Dynamic preservation strategies are a promising option to improve graft quality before transplantation, and to extend preservation time for either logistic or treatment reasons. In contrast to normothermic oxygenated perfusion, which intends to mimic physiological conditions in the human body, with subsequent clinical application for up to 24 hrs, hypothermic perfusion is mainly used for a relatively short period with protection of mitochondria and subsequent reduction of oxidative injury upon implantation. The results from two randomized controlled trials, where recruitment has finished are expected this year. Both ex situ perfusion techniques are increasingly applied in clinical transplantation including recent reports on viability assessment, which could open the door for an increased liver utilization in the future.


Grape seed proanthocyanidin extract promotes skeletal muscle fiber type transformation via AMPK signaling pathway.
Transformation of skeletal muscle fiber type from fast twitch to slow twitch has significances for sustained contractile and stretchable events, energy homeostasis and antifatigue ability. However, the regulation of skeletal muscle fiber type transformation through nutritional intervention is still not fully spelled out. Grape seed proanthocyanidin extract (GSPE) has been widely reported to play a broader role in many aspects of diseases with its various pharmacological and health-promoting effects. In this study, we found that GSPE significantly improved the fatigue resistance in mice. GSPE up-regulated slow myosin heavy chain (MyHC) and down-regulated fast MyHC, accompanied by increases in activities of succinic dehydrogenase and malate dehydrogenase and by decreased lactate dehydrogenase activity in muscle of mice and in C2C12 myotubes. The AMP-activated protein kinase (AMPK) signaling can be activated by GSPE. Several upstream and downstream factors of AMPK signaling such as liver kinase B1, nuclear respiratory factor 1, calcium calmodulin-dependent protein kinase kinase β, sirtuin1 and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) were also up-regulated by GSPE. Specific inhibition of AMPK signaling by AMPK inhibitor compound C or by AMPKα1 siRNA significantly abolished the GSPE-induced the activation of AMPK and the increase of PGC-1α, and attenuated the GSPE-induced increase of slow MyHC and decrease of fast MyHC in C2C12 myotubes. Taken together, we revealed that GSPE promotes skeletal muscle fiber type transformation from fast twitch to slow twitch through AMPK signaling pathway, and this GSPE-induced fiber type transformation may contribute to increased fatigue resistance.


A possible role for deoxyribonucleotide pool imbalances in carcinogenesis.
Thymine nucleotide pool alterations, produced by attack on non-DNA primary targets, induce a variety of chromosome and chromatid aberrations. Specifically, in lower eukaryotes, thymidylate deprivation and excess are recombinagenic and dTMP depletion also produces DNA strand breakage. In higher eukaryotes, imbalances in thymine nucleotide pools provoke chromosome breaks and rearrangements, and inhibition of thymidylate biosynthesis causes morphological and oncogenic transformation in vitro. Thus, chromosomal rearrangements induced by dTMP deprivation may be the critical changes that lead to oncogenic transformation in response to thymine nucleotide depletion.


[Results of FDG-PET scanning in the pre-operative staging of broncho-pulmonary tumors].
Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) has recently established itself as an important imaging strategy in the management of respectable non-small cell bronchial carcinoma (NSCLC). In this study we report our experience of the impact of FDG-PET in the pre-operative assessment of NSCLC. In a single centre retrospective study between 01 January 2000 and 31 Dec 2002, 108 FDGPET scans were performed during the preoperative assessment of histologically proven or strongly suspected NSCLC. The sensitivity, specificity and accuracy of FDG-PET for the characterization of a parenchymatous opacity were 96%, 71% and 92% respectively (4 false negatives, 5 false positives). The sensitivity, specificity and accuracy for mediastinal node involvement were 62%, 94% and 84% respectively (10 false negatives and 4 false positives). The sensitivity, specificity and accuracy for the characterization of adrenal nodules were 88%, 100% and 97% (1 false negative) and for satellite pulmonary nodules 50%, 75% and 64% (2 false negatives and 3 false positives). FDG-PET is a useful imaging modality in the pre-operative management of NSCLC but is limited particularly in the characterization of lesions less than 10 mm in diameter and in the evaluation of mediastinal lymph nodes.


Diuretic therapies in low renin and normal renin essential hypertension.
This study was designed to compare the effectiveness of spironolactone, hydrochlorothiazide, and combined spironolactone-hydrochlorothiazide therapy in patients with low renin and those with normal renin essential hypertension. Patients with low renin hypertension had a greater hypotensive response to each regimen (p less than 0.001). Low renin patients responded equally to both spironolactone and to hydrochlorothiazide, and in low renin but not in normal renin patients reduction of blood pressure correlated with weight loss. These results suggest that a volume factor, not specifically related to increased mineralocorticoid production, contributes to the pathogenesis of low renin essential hypertension.


A New Mexican Species of Orizabus Fairmaire (Coleoptera: Scarabaeidae: Dynastinae: Pentodontini), with a Key to the Species of the Genus.
A new Orizabus species is described from Chilapa de Álvarez in the state of Guerrero (Mexico). The new species is similar to Orizabus rawlinsi Dechambre Bull Soc Entomol Fr 98:342, 1993, which is known from the state of Oaxaca but differs in the pygidial punctation, and the shape of the marginal pronotal bead and the parameres. A revised identification key to Orizabus species is provided.


Lack of association between XPD Lys751Gln and Asp312Asn polymorphisms and colorectal cancer risk: a meta-analysis of case-control studies.
The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln and Asp312Asn polymorphisms and colorectal cancer remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A comprehensive literature search was conducted to identify all case-control studies of Lys751Gln and Asp312Asn polymorphisms on the susceptibility of different tumor site of colorectal cancer (colon, rectum, and colon/rectum cancer). A total of 22 eligible studies were selected for this meta-analysis, including 3,042 cases and 4,627 controls for Lys751Gln and 1,581 cases and 2,846 controls for Asp312Asn. Overall, no significantly elevated colorectal cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (for Lys751Gln polymorphism: Lys/Gln vs. Lys/Lys, OR = 1.01, 95% CI = 0.90-1.14; Gln/Gln vs. Lys/Lys, OR = 1.04, 95% CI = 0.85-1.26; dominant model, OR = 1.03, 95% CI = 0.93-1.15; recessive model, OR = 1.04, 95% CI = 0.87-1.25; and for Asp312Asn polymorphism: Asp/Asn vs. Asp/Asp, OR = 1.11, 95% CI = 0.91-1.35; Asn/Asn vs. Asp/Asp, OR = 1.13, 95% CI = 0.87-1.47; dominant model, OR = 1.09, 95% CI = 0.94-1.26; recessive model, OR = 1.11, 95% CI = 0.88-1.41). And for the additive model, individuals carrying the 751Gln or 312Asn allele were not significantly associated with increased risk to colorectal cancer (OR = 1.02, 95% CI = 0.94-1.11, OR = 1.07, 95% CI = 0.95-1.20). This meta-analysis suggests that XPD Lys751Gln and Asp312Asn polymorphisms may not be associated with colorectal cancer development.


Cardiovascular and sympathetic nerve responses induced by intracerebroventricular injections of prostacyclin in rats.
Intracerebroventricular (ICV) injections of prostacyclin (PGI2) produced biphasic blood pressure responses consisting of an initial hypotensive phase followed by a sustained pressor phase in awake rats. Heart rate increased following such injections in either awake or anesthetized rats. PGI2, 1 microgram, produced biphasic responses and, 10 micrograms, purely vasodepressor responses in anesthetized rats, but abdominal sympathetic nerve firing recorded was consistently increased. Hypophysectomy did not affect the hypotensive phase of the responses. These results indicate that the initial hypotension can not be explained by centrally-induced changes in sympathetic nerve activity or vasopressin release, but may be due to peripheral effects of PGI2 leaking from the injection site.


The intracellular pH of tunicate blood cells: Ascidia ceratodes whole blood, morula cells, vacuoles and cytoplasm.
The intracellular pH of blood cells of the tunicate Ascidia ceratodes has been measured by equilibration of radioactively labeled markers between intra- and extracellular media. Labeled acid, 5,5-dimethyloxazolidine-2,4-dione (DMO), and base, methylamine (MA), have been used in the range of extracellular pH (pHm) of 4.5-7. For unsorted blood cells MA is less sensitive to the transmembrane pH gradient (delta pH) than is DMO in the pHm of 6.3-7. The data measured by DMO yield an intracellular pH value of 6.98 +/- 0.15. Ficoll density gradients separated 86.4% pure morula cells. Other experiments show that morula cells contain significant amounts of vanadium and most of the free tunichrome. Using both MA and DMO with morula cells yields pH values of 5.0 +/- 0.2 for the vacuoles and 7.1 +/- 0.2 for the cytoplasm. If vanadium is accumulated in the intravacuolar solution space, then this mildly acidic pH indicates that the aquo V3+ ion, which is only stable below pH 3, is stabilized by some factor other than high hydrogen ion concentration. This factor may be chelation by tunichrome. It is also possible that accumulated vanadium(III) is sequestered in hydrophobic regions of the vacuolar or cellular membranes.


Beyond simultaneity: Temporal interdependence of behavior is key to affiliative effects of interpersonal synchrony in children.
Interpersonal synchrony (IPS) is the temporal coordination of behavior during social interactions. IPS acts as a social cue signifying affiliation both when children witness IPS between others and when they experience it themselves. However, it is unclear which temporal qualities of IPS produce these effects and why. We hypothesized that both the simultaneity and temporal regularity of partners' actions would influence affiliation judgments and that subjective perceptions of IPS ("togetherness") would play a role in mediating these relations. In two online tasks, children aged 4 to 11 years listened to a pair of children tapping (witnessed IPS; n = 68) or themselves tapped with another child (experienced IPS; n = 63). Tapping partners were presented as real, but the sounds attributed to them were computer generated so that their temporal relations could be experimentally manipulated. The simultaneity and regularity of their tapping was systematically manipulated across trials. For witnessed IPS, both the simultaneity and regularity of partners' tapping significantly positively affected the perceived degree of affiliation between them. These effects were mediated by the perceived togetherness of the tapping. No affiliative effects of IPS were found in the experienced IPS condition. Our findings suggest that both the simultaneity and regularity of partners' actions influence children's affiliation judgments when witnessing IPS via elicited perceptions of togetherness. We conclude that temporal interdependence-which includes but is not limited to simultaneity of action-is responsible for inducing perceptions of affiliation during witnessed IPS.


Alpha 2-adrenergic receptor function in patients with unipolar and bipolar affective disorders.
Alpha 2-adrenergic receptor function was measured in platelets from unipolar (UP) depressed, bipolar (BP) depressed, and bipolar euthymic patients and normal control subjects. Only the platelets from UP depressed patients were different from control in having an increased number of alpha 2-receptors, a decreased percent norepinephrine inhibition of prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) production, and a decrease in PGE1 stimulation of cAMP production. Platelets from BP patients, depressed or euthymic, were not significantly different from control subjects. These preliminary data suggest that alpha 2-adrenergic receptor function and PGE1 stimulation of cAMP production are diminished in UP patients.


An improved method of gene synthesis based on DNA works software and overlap extension PCR.
A bottleneck in recent gene synthesis technologies is the high cost of oligonucleotide synthesis and post-synthesis sequencing. In this article, a simple and rapid method for low-cost gene synthesis technology was developed based on DNAWorks program and an improved single-step overlap extension PCR (OE-PCR). This method enables any DNA sequence to be synthesized with few errors, then any mutated sites could be corrected by site-specific mutagenesis technology or PCR amplification-assembly method, which can amplify different DNA fragments of target gene followed by assembly into an entire gene through their overlapped region. Eventually, full-length DNA sequence without error was obtained via this novel method. Our method is simple, rapid and low-cost, and also easily amenable to automation based on a DNAWorks design program and defined set of OE-PCR reaction conditions suitable for different genes. Using this method, several genes including Manganese peroxidase gene (Mnp) of Phanerochaete chrysosporium (P. chrysosporium), Laccase gene (Lac) of Trametes versicolor (T. versicolor) and Cip1 peroxidase gene (cip 1) of Coprinus cinereus (C. cinereus) with sizes ranging from 1.0 kb to 1.5 kb have been synthesized successfully.


Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study.
15% of women treated for high-grade cervical intraepithelial neoplasia (CIN grade 2 or 3) develop residual or recurrent CIN grade 2 or 3 or cervical cancer, most of which are diagnosed within 2 years of treatment. To gain more insight into the long-term predictive value of different post-treatment strategies, we assessed the long-term cumulative risk of post-treatment CIN grade 2 or 3 or cancer and different follow-up algorithms to identify women at risk of residual or recurrent disease. Women who were included in three studies in the Netherlands and who were treated for CIN grade 2 or 3 between July, 1988, and November, 2004, were followed up by cytology and testing for high-risk human papillomavirus (hrHPV) at 6, 12, and 24 months after treatment, and subsequently received cytological screening every 5 years. The primary endpoint was the cumulative risk of post-treatment CIN grade 2 or higher by December, 2009. We also assessed the cumulative risk of CIN grade 2 or higher in women with three consecutive negative cytological smears and women with negative co-testing with cytology and hrHPV at months 6 and 24. This study is registered in the Dutch trial register, NTR1468. 435 women were included, 76 (17%) of whom developed post-treatment CIN grade 2 or higher, of which 39 were CIN grade 3 or higher. The 5-year risk of developing post-treatment CIN grade 2 or higher was 16·5% (95% CI 13·0-20·7) and the 10-year risk was 18·3% (13·8-24·0). The 5-year risk of developing post-treatment CIN grade 3 or higher was 8·6% (95% CI 6·0-12·1) and the 10-year risk was 9·2% (5·8-14·2). Women with three consecutive negative cytological smears had a CIN grade 2 or higher risk of 2·9% (95% CI 1·2-7·1) in the next 5 years and of 5·2% (2·1-12·4) in the next 10 years. The 5-year risk of CIN grade 3 or higher was 0·7% (95% CI 0·0-3·9) and the 10-year risk was 0·7% (0·0-6·3). Women with negative results for co-testing had a 5-year risk of CIN grade 2 or higher of 1·0% (95% CI 0·2-4·6) and a 10-year risk of 3·6% (1·1-10·7). The 5-year risk of CIN grade 3 or higher was 0·0% (95% CI 0·0-3·0) and the 10-year risk was 0·0% (0·0-5·3). The 5-year risk of post-treatment CIN grade 2 or higher in women with three consecutive negative cytological smears or negative co-testing for cytology and hrHPV at 6 and 24 months was similar to that of women with normal cytology in population-based screening and therefore justifies their return to regular screening. VU University Medical Center, Erasmus University Medical Center, Netherlands.


Electrochemical Generation of Hypervalent Bromine(III) Compounds.
In sharp contrast to hypervalent iodine(III) compounds, the isoelectronic bromine(III) counterparts have been little studied to date. This knowledge gap is mainly attributed to the difficult-to-control reactivity of λ3 -bromanes as well as to their challenging preparation from the highly toxic and corrosive BrF3 precursor. In this context, we present a straightforward and scalable approach to chelation-stabilized λ3 -bromanes by anodic oxidation of parent aryl bromides possessing two coordinating hexafluoro-2-hydroxypropanyl substituents. A series of para-substituted λ3 -bromanes with remarkably high redox potentials spanning a range from 1.86 V to 2.60 V vs. Ag/AgNO3 was synthesized by the electrochemical method. We demonstrate that the intrinsic reactivity of the bench-stable bromine(III) species can be unlocked by addition of a Lewis or a Brønsted acid. The synthetic utility of the λ3 -bromane activation is exemplified by oxidative C-C, C-N, and C-O bond forming reactions.


Dampening of death pathways by schnurri-2 is essential for T-cell development.
Generation of a diverse and self-tolerant T-cell repertoire requires appropriate interpretation of T-cell antigen receptor (TCR) signals by CD4(+ ) CD8(+) double-positive thymocytes. Thymocyte cell fate is dictated by the nature of TCR-major-histocompatibility-complex (MHC)-peptide interactions, with signals of higher strength leading to death (negative selection) and signals of intermediate strength leading to differentiation (positive selection). Molecules that regulate T-cell development by modulating TCR signal strength have been described but components that specifically define the boundaries between positive and negative selection remain unknown. Here we show in mice that repression of TCR-induced death pathways is critical for proper interpretation of positive selecting signals in vivo, and identify schnurri-2 (Shn2; also known as Hivep2) as a crucial death dampener. Our results indicate that Shn2(-/-) double-positive thymocytes inappropriately undergo negative selection in response to positive selecting signals, thus leading to disrupted T-cell development. Shn2(-/-) double-positive thymocytes are more sensitive to TCR-induced death in vitro and die in response to positive selection interactions in vivo. However, Shn2-deficient thymocytes can be positively selected when TCR-induced death is genetically ablated. Shn2 levels increase after TCR stimulation, indicating that integration of multiple TCR-MHC-peptide interactions may fine-tune the death threshold. Mechanistically, Shn2 functions downstream of TCR proximal signalling compenents to dampen Bax activation and the mitochondrial death pathway. Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation.


Author Correction: Automatic diagnosis of the 12-lead ECG using a deep neural network.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults.
Berry-derived phenolic compounds found in grapes have been associated with a number of health benefits, including the augmentation of human brain function and cognition. Previous intervention studies of Concord grape juice have demonstrated improvement to memory and driving ability following 3- to 4-month supplementation in middle-aged and older adults. However, no studies to date have demonstrated acute cognitive benefits of grape juice, and investigation of these effects in young adults is lacking. This randomised, placebo-controlled, double-blind, counterbalanced-crossover study, assessed the effects of 230 ml purple grape juice or sugar-matched control in 20 healthy young adults. Computerised measures of episodic memory, working memory, attention and mood were completed at baseline and following a 20-min absorption period. Purple grape juice significantly improved reaction time on a composite attention measure (p = 0.047) and increased calm ratings (p = 0.046) when compared to placebo. Order effects also indicated an enduring positive effect on pre-dose memory reaction time (p = 0.018) and post-dose calm ratings (p = 0.019) when purple grape was consumed first. These findings in a small sample of healthy young adults suggest that purple grape juice can acutely enhance aspects of cognition and mood. No significant effects of juice were observed on memory measures, suggesting that these may be less susceptible to manipulation following acute supplementation in healthy young adults. Potential mechanisms underlying these effects include modulation of cerebral blood flow, glucoregulation and inhibition of monoamine oxidase activity, all of which require further exploration.


The effect of nucleus pulposus crosslinking and glycosaminoglycan degradation on disc mechanical function.
Altered mechanical loading, secondary to biochemical changes in the nucleus pulposus, is a potential mechanism in disc degeneration. An understanding of the role of this altered mechanical loading is only possible by separating the mechanical and biological effects of early nucleus pulposus changes. The objective of this study was to quantify the mechanical effect of decreased glycosaminoglycans (GAG) and increased crosslinking in the nucleus pulposus using in vitro rat lumbar discs. Following initial mechanical testing the discs were injected according to the four treatment groups: PBS control, chondroitinase-ABC (ChABC) for GAG degradation, genipin (Gen) for crosslinking, or a combination of chondroitinase and genipin (ChABC+Gen). After treatment the discs were again mechanically tested, followed by histology or biochemistry. Neutral zone mechanical properties were changed by approximately 20% for PBS, ChABC, and ChABC+Gen treatments (significant only for PBS in a paired comparison). These trends were reversed with genipin crosslinking alone. With ChABC treatment the effective compressive modulus increased and the GAG content decreased; with the combination of ChABC+Gen the mechanics and GAG content were unchanged. Degradation of nucleus pulposus GAG alters disc axial mechanics, potentially contributing to the degenerative cascade. Crosslinking is unlikely to contribute to degeneration, but may be a potential avenue of treatment.


Some new biologically active metal-based sulfonamide.
A new series of sulfonamide derived Schiff bases has been synthesized by a condensation reaction of various sulfonamides with aromatic aldehydes. The so obtained sulfonamide were further investigated for their chelation and biological properties with first row d-transition metal ions [cobalt(II), copper(II), nickel(II) and zinc(II)]. The nature of bonding and structure of all the synthesized compounds have been inferred from magnetic susceptibility and conductivity measurements, IR, (1)H and (13)C NMR, electronic spectral, mass spectrometry and CHN analysis data. The structure of ligand, 4-{[(E)-(5-bromo-2-hydroxy phenyl)methylidene]amino}-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide has also been determined by X-ray diffraction method. An octahedral geometry has been suggested for all the complexes. The ligands and their metal complexes have been screened for in vitro antibacterial, antifungal and cytotoxic properties. The result of these studies have revealed that all compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against various fungal strains.


Result of a pyrocarbon prosthesis after comminuted and unreconstructable radial head fractures.
The purpose of this study is to analyze the results of treating unreconstructable acute radial head fractures associated with other elbow fractures and soft-tissue injuries with a pyrocarbon radial head prosthesis replacement, as well as repair of the associated injuries. Twenty-eight patients with Mason type III unreconstructable and unstable radial head fractures and with associated injuries (according to Hotchkiss classification modified by van Riet) were treated with a pyrocarbon radial head prosthesis replacement; repair of collateral ligaments and associated elbow fractures was also carried out. Patients were evaluated in accordance with the Mayo Elbow Performance Score, measuring pain, grip strength, range of motion, and stability, as well as radiographic images. After a mean of 32 months postoperatively (range, 12-62 months), the mean Mayo Elbow Performance Score was 92 points. The result was considered excellent or good in 25 patients, with a high degree of satisfaction and functional restoration. The results of treating Mason type III radial head fractures with additional elbow fractures and soft-tissue injuries with pyrocarbon radial head prostheses are satisfactory; nevertheless, long-term follow-up is still necessary.


Accuracy and dosimetric parameters comparison of 3D-printed non-coplanar template-assisted computed tomography-guided iodine-125 seed ablative brachytherapy in pelvic lateral recurrence of gynecological carcinomas.
To investigate the accuracy of needle distribution and dosimetric parameter differences of 3D-printing non-coplanar template (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 seed ablative brachytherapy (125I-SAB) in gynecological cancer patients with non-central pelvic recurrence between pre-operative plan and post-operative plan. Thirty-eight patients with forty-one non-central pelvic recurrent gynecological carcinomas after radiotherapy were enrolled in this study. All patients received 3D-PNCT-assisted CT-guided 125I-SAB from January 2016 to January 2019. The position, angle, and depth of seed needles were measured in both pre-operative plan and intra-operative real-time plan in brachytherapy treatment planning system (B-TPS). Dosimetric parameters of D90, D100, V100, V150, and V200 as well as quality parameters of conformal index (CI), external index (EI), and homogeneity index (HI) were compared between pre-operative plan and post-operative plan. Peri-operation complications and radiation-related toxicity were assessed. Median follow-up time was 12 months (range, 5-34 months). Prescribed dose was 100-170 Gy (median, 120 Gy). Radioactivity of 125I seed was 0.4-0.7 mCi (median, 0.55 mCi). Mean depth deviation for 499 needles was 0.8 ±1.0 cm. Mean angular deviation was 2.2 ±2.1 degrees. Mean tip distance deviation of needles was 0.4 ±0.3 cm. There were significant differences between pre-operative and post-operative plans in CI (p = 0.001) and EI (p = 0.005). No significant differences were shown in D90, D100, V100, V150, V200, and HI between pre-operative and post-operative plans. Only few patients suffered from ≤ grade 2 toxicities. 3D-PNCT-assisted CT-guided 125I-SAB is safe and feasible for non-central pelvic recurrence of gynecological cancer. All complications are tolerable and mild.


Effectiveness of exercise interventions to prevent shoulder injuries in athletes: a systematic review protocol.
This review will evaluate the effectiveness of exercise intervention versus no intervention or alternate intervention to prevent shoulder injuries in athletes. Injury-prevention research has proven the effectiveness of exercise in preventing sports injuries in general and in the lower limb specifically. However, the results have been extrapolated to sport-related shoulder injuries from limited evidence. Similar reviews have been faced with insufficient high-quality evidence and limited studies due to restrictive target populations, resulting in reduced generalizability. Peer-reviewed randomized controlled trials, with adequate control arms, investigating shoulder-injury events after exercise intervention in athletes, both training or competing in sports, will be included. Studies with substitute end points for injury events and non-self-propelled athletes, or vehicle-assisted athletes, will be excluded. A comprehensive search of multiple databases will be used to find relevant studies. The databases will be searched from inception to April 2021, with no language restrictions imposed. Keywords and derivatives of "sport," "exercise intervention," "prevention," "shoulder injury," and "randomized controlled trials" will be used.Sources will include Academic Search Ultimate (EBSCO), CINAHL Plus (EBSCO), Cochrane Central Register of Controlled Trials (Wiley), MasterFILE Premier (EBSCO), MEDLINE (PubMed), Physiotherapy Evidence Database (PEDro), ProQuest Health and Medical Complete and Nursing and Allied Health Source (ProQuest Complete), ScienceDirect (Elsevier), Scopus (Elsevier), SPORTDiscus (EBSCO), and Web of Science (Clarivate Analytics). Data appraisal, extraction, and synthesis will follow JBI guidance for systematic reviews of effectiveness. PROSPERO CRD42020204141.


Transcriptome Profile Analysis of Intestinal Upper Villus Epithelial Cells and Crypt Epithelial Cells of Suckling Piglets.
It is well known that the small intestinal epithelial cells of mammals rapidly undergo differentiation, maturation, and apoptosis. However, few studies have defined the physiological state and gene expression changes of enterocytes along the crypt-villus axis in suckling piglets. In the present study, we obtained the intestinal upper villus epithelial cells (F1) and crypt epithelial cells (F3) of 21-day suckling piglets using the divalent chelation and precipitation technique. The activities of alkaline phosphatase, sucrase, and lactase of F1 were significantly higher (p < 0.05) than those of F3. To explore the differences at the gene transcription level, we compared the global transcriptional profiles of F1 and F3 using RNA-seq analysis technology. A total of 672 differentially expressed genes (DEGs) were identified between F1 and F3, including 224 highly expressed and 448 minimally expressed unigenes. Functional analyses indicated that some DEGs were involved in the transcriptional regulation of nutrient transportation (SLC15A1, SLC5A1, and SLC3A1), cell differentiation (LGR5, HOXA5 and KLF4), cell proliferation (PLK2 and TGFB3), transcriptional regulation (JUN, FOS and ATF3), and signaling transduction (WNT10B and BMP1), suggesting that these genes were related to intestinal epithelial cell maturation and cell renewal. Gene Ontology (GO) enrichment analysis showed that the DEGs were mainly associated with binding, catalytic activity, enzyme regulator activity, and molecular transducer activity. Furthermore, KEGG pathway analysis revealed that the DGEs were categorized into 284 significantly enriched pathways. The greatest number of DEGs enriched in signal transduction, some of which (Wnt, Hippo, TGF-beta, mTOR, PI3K-Akt, and MAPK signaling pathways) were closely related to the differentiation, proliferation, maturation and apoptosis of intestinal epithelial cells. We validated the expression levels of eight DEGs in F1 and F3 using qRT-PCR. The present study revealed temporal and regional changes in mRNA expression between F1 and F3 of suckling piglets, which provides insights into the regulatory mechanisms underlying intestinal epithelial cell renewal and the rapid repair of intestinal mucosal damage.


Functional Bph14 from Rathu Heenati promotes resistance to BPH at the early seedling stage of rice (Oryza sativa L.) as revealed by QTL-seq.
A QTL associated with BPH resistance at the early seedling stage was identified on chromosome 3. Functional Bph14 in Rathu Heenati was associated with BPH resistance at the early seedling stage. Brown planthopper (BPH; Nilaparvata lugens Stål) is considered the most important rice pest in many Asian countries. Several BPH resistance genes have previously been identified. However, there are few reports of genes specific for BPH resistance at the early seedling stage, a crucial stage for direct-seeding cultivation. In this study, we performed a QTL-seq analysis using two bulks (20 F2 lines in each bulk) of the F2 population (n = 300) derived from a cross of Rathu Heenati (RH) × HCS-1 to identify QTL/genes associated with BPH resistance at the early seedling stage. An important QTL was identified on chromosome 3 and Bph14 was identified as a potential candidate gene based on the differences in gene expression and sequence variation when compared with the two parents. All plants in the resistant bulks possessed the functional Bph14 from RH and all plants in the susceptible bulk and HCS-1 contained a large deletion (2703 bp) in Bph14. The functional Bph14 gene of RH appears to be important for BPH resistance at the early seedling stage of rice and could be used in conjunction with other BPH resistance genes in rice breeding programs that confer resistance to BPH at the early and later growth stages.


Optical detection systems using immobilized aptamers.
Advances in the development and the applications of optical biosensing systems based on immobilized aptamers are presented. These nucleic acid sequences have been used as new molecular recognition elements to develop heterogeneous assays, biosensors and microarrays. Among different detection modes that have been employed, optical ones which are described here are among the most used. Since their first report in 1996, numerous optical detection systems using aptamers and mainly based on fluorescence have been developed. Two main approaches have been used: label-based (using fluorophore, luminophore, enzyme, nanoparticles) or aptamer label-free detection systems (e.g. surface plasmon resonance, optical resonance). Most methods are based on a labeling approach. Some targets can be optically detected using not only colorimetry, chemiluminescence or the most developed fluorescence mode but also more recent non conventional optical methods such as surface plasmon-coupled directional emission (SPCDE). The first SPCDE-based aptasensor for thrombin detection has recently been reported in 2009. Aptasensors based on surface-enhanced Raman scattering spectroscopy (SERS) which presents advantages compared to fluorescence have also been described. Different label-free techniques have recently been shown to be suitable for developing performant aptasensors or aptamer-based microarrays, such as surface plasmon resonance (SPR), diffraction grating, evanescent-field-coupled (EFC) waveguide-mode, optical resonance or Brewster angle straddle interferometry (BASI). Important advances have been realized on optical aptamer-based detection systems that appear as highly efficient devices with enormous potential.


Should total thyroidectomies be performed by high-volume endocrine surgeons? A cost-effectiveness analysis.
The increased experience of a thyroid surgeon reduces the risk of postoperative complications. However, whether it is also cost-effective is currently unknown. The aim of the present study was to compare cost-effectiveness of high-volume (HVS) with low-volume surgeons (LVS) when performing a total thyroidectomy. This was a retrospective study, comparing the mean cost of a total thyroidectomy per patient, between HVS and LVS. This included the cost of surgical procedure and pre- and post-operative inpatient hospitalization. A threshold of 25 thyroidectomies/year was used to discriminate between HVS and LVS. Four-hundred and forty-one patients were classified into HVS and 342 into the LVS group. With regard to surgical complications, higher rates of temporary hypoparathyroidism and endangered airway were observed in the LVS than in the HVS group. The estimated total cost per patient was higher in the LVS compared with the HVS group [€1721 ± 396 ($1910 ± 439) versus €979 ± 68 ($1086 ± 487); p < 0.0001]. This cost remained higher when sub-analysis was performed for each surgical stage, involving either surgical procedure or pre- and post-operative inpatient hospitalization. Differences between LVS and HVS mainly involved the cost in surgical procedure (23% attributed to occupation of the operating room) and postoperative inpatient hospitalization (45% of the total thyroidectomy cost). Total thyroidectomy performed by a HVS seems to be cost-effective compared with the one conducted by LVS. This is mostly attributed to the lower rates of surgical complications, such as postoperative hypoparathyroidism and airway obstruction.


Pilot trial of iBDecide: Evaluating an online tool to facilitate shared decision making for adolescents and young adults with ulcerative colitis.
This pilot, randomized controlled trial aimed to evaluate the usability, among adolescents and young adults (AYAs) with ulcerative colitis (UC), of a web-based tool ('iBDecide') designed to facilitate shared decision making (SDM). AYAs with UC (n = 35) were randomized to intervention (iBDecide, n = 14) and control (n = 12) arms before a scheduled clinic visit. We measured the usability of iBDecide, SDM, preferred decision-making style, decision conflict and intervention use. Participants in the intervention group found iBDecide easy to use and agreed that it made them feel ready to participate in decision making and that they would use it to prepare for appointments. There were 130 visits to iBDecide, lasting on average 3 min, 41 s. The medication and nutrition trackers were among the most-viewed pages. Pages specifically designed to facilitate SDM were viewed only four times. Across groups, too few participants reported making decisions during clinic visits for decision-related measures to be reported. This pilot trial provides evidence for the usability of iBDecide and guidance for developing a larger-scale trial of a combined web-based and in-clinic SDM intervention. Overall, iBDecide shows promise in engaging AYAs with UC in SDM and condition management. Patients, specifically AYAs with UC, and healthcare providers were involved in the design of this study's intervention, iBDecide. Additionally, the research team, from study conception to manuscript writing, included a young adult with inflammatory bowel disease. This study was registered at clinicaltrials.gov (NCT04207008).


Fatty acid ethyl ester synthesis by human liver microsomes.
Fatty acid ethyl esters are a family of non-oxidative metabolites of ethanol present in many tissues after ethanol consumption. In this report we demonstrate the existence in human liver of an acyl-CoA:ethanol acyltransferase activity which may be responsible in part for the synthesis of these compounds in vivo. The effects of oleoyl-CoA and ethanol concentrations, presence or absence of bovine serum albumin and detergent, pH and enzyme concentration on this activity have been determined. Acyl-CoA:ethanol acyltransferase activity is localised in the membrane-bound fraction. Using inhibitors directed against related enzyme activities, it has been shown that the activity is not related to serine-dependent carboxylesterases or acyl-CoA:cholesterol acyltransferase, but tht it may be associated with acyl-CoA hydrolase activity. We have also compared acyl-CoA:ethanol acyltransferase activity with fatty acid ethyl ester synthase activity in microsomes and cytosol from the same liver. Our data indicate that these activities are comparable in vitro (on a unit/g liver basis), and suggest that both may be significant in vivo.


Evaluation of a new disposable flexible ureterorenoscope and comparison to an established disposable flexible ureterorenoscope: a prospective, observational study.
To objectively and subjectively assess the performance and surgical outcomes of the new Innovex EU-scope™ single-use digital flexible ureteroscope (fURS). A prospective cohort study was carried out (August 2019 to May 2020). The new single-use fURS (Innovex Medical Devices Co. Shanghai, China) was analysed with regard to visibility, manoeuvrability, laser interference and overall performance using a validated Likert scale. Outcomes are compared to the LithoVue™ (Boston Scientific, Marlborough, MA). One hundred patients were included in this study. 50 cases underwent retrograde fURS using the Innovex EU-scope™ and 50 with the LithoVue™. There were no differences in the patient demographics data, or operative data between the two groups. The Innovex EU-scope™ scored higher visibility scores compared to the LithoVue™, median 4, interquartile range (IQR) (4-4), vs. 3.5, IQR (3-5), p = 0.5086. Both scopes had similar manoeuvrability scores. The Innovex EU-scope™ scored significantly lower with regard to comfort compared to the LithoVue, median 4 IQR (3-4) vs. 4.5 IQR (4-5), p = 0.0445. Whereas, laser interference, affected the Innovex much less than the LithoVue™. Both scopes scored well for overall performance. The median overall performance score for the Innovex was 4 IQR (4-4) vs. 4 IQR (4-5). This Innovex EU-scope™ has good objective and subjective visibility and manoeuvrability profiles. This single-use flexible ureteroscope may achieve similar clinical outcomes to an established single use instrument.


Investigation on nanoparticle distribution for thermal ablation of a tumour subjected to nanoparticle assisted thermal therapy.
This study investigates the effect of the distribution of nanoparticles delivered to a skin tumour for the thermal ablation conditions attained during thermal therapy. Ultimate aim is to define a distribution of nanoparticles as well as a combination of other therapeutic parameters to attain thermal ablation temperatures (50-60 °C) within whole of the tumour region. Three different cases of nanoparticle distributions are analysed under controlled conditions for all other parameters viz. irradiation intensity and duration, and volume fraction of nanoparticles. Results show that distribution of nanoparticles into only the periphery of tumour resulted in desired thermal ablation temperature in whole of tumour. For the tumour size considered in this study, an irradiation intensity of 1.25 W/cm(2) for duration of 300 s and a nanoparticle volume fraction of 0.001% was optimal to attain a temperature of ≥53 °C within the whole tumour region. It is concluded that distribution of nanoparticles in peripheral region of tumour, along with a controlled combination of other parameters, seems favourable and provides a promising pathway for thermal ablation of a tumour subjected to nanoparticle assisted thermal therapy.


The 2016 ENFSI Fingerprint Working Group testing programme.
In 2016, the Fingerprint Working Group (EFP-WG) of the European Network of Forensic Science Institutes (ENFSI), officially established an advisory group with the task of organising proficiency tests (PTs), as well as collaborative exercises (CEs) as a way of raising standards within the fingerprint profession. This article will provide an overview of the Visualisation collaborative exercise and the Comparison proficiency test, which were carried out in 2016. Both the exercise and the test were organised and co-funded by the Prevention of and Fight against Crime Programme of the European Union [1-3], Direct Grant "Towards the Vision for European Forensic Science 2020 (TVEFS-2020)" HOME/2013/ISEC/MO/ENFSI/4000005962, work package T3 "Proficiency Tests and Collaborative Exercises for the Fingerprint Domain". The characteristics of the testing programme are summarised, followed by an overview of the knowledge that has been gained, including lessons learnt.


A preliminary evaluation of alternative adjuvants to alum using a range of established and new generation vaccine antigens.
Although alum is the most commonly used vaccine adjuvant, it has some limitations for use with the next generation recombinant antigens. We explored the use of alternative adjuvant formulations (poly lactide co-glycolide (PLG) microparticles, MF59 emulsion, CAP and l-tyrosine suspension) in comparison with five different vaccine antigens--namely, diphtheria toxoid (DT), tetanus toxoid (TT), HBsAg, Men C conjugate and MB1. The results indicated that although alum was optimal for bacterial toxoid based vaccines, it was not highly potent for MB1, Men C or HBsAg antigens. MF59 emulsion stood out as a good alternative to alum for TT, HBsAg, MB1 and Men C vaccines. On the other hand l-tyrosine suspension and CAP did not enhance immune responses over alum with most antigens. PLG microparticles were comparable or better than alum with both MB1 and Men C conjugate vaccine. The study indicates that it is possible to replace alum with other adjuvant formulations like MF59 and PLG and maintain and/or improve immune responses with some vaccine antigens.


Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning.
Disability progression in multiple sclerosis remains resistant to treatment. The absence of a suitable biomarker to allow for phase 2 clinical trials presents a high barrier for drug development. We propose to enable short proof-of-concept trials by increasing statistical power using a deep-learning predictive enrichment strategy. Specifically, a multi-headed multilayer perceptron is used to estimate the conditional average treatment effect (CATE) using baseline clinical and imaging features, and patients predicted to be most responsive are preferentially randomized into a trial. Leveraging data from six randomized clinical trials (n = 3,830), we first pre-trained the model on the subset of relapsing-remitting MS patients (n = 2,520), then fine-tuned it on a subset of primary progressive MS (PPMS) patients (n = 695). In a separate held-out test set of PPMS patients randomized to anti-CD20 antibodies or placebo (n = 297), the average treatment effect was larger for the 50% (HR, 0.492; 95% CI, 0.266-0.912; p = 0.0218) and 30% (HR, 0.361; 95% CI, 0.165-0.79; p = 0.008) predicted to be most responsive, compared to 0.743 (95% CI, 0.482-1.15; p = 0.179) for the entire group. The same model could also identify responders to laquinimod in another held-out test set of PPMS patients (n = 318). Finally, we show that using this model for predictive enrichment results in important increases in power.


Synergistic actions of Ca2+ and the phorbol ester TPA on K+-induced catecholamine release from bovine adrenal chromaffin cells.
Enhancement of Ca2+-dependent high K+-evoked catecholamine secretion was observed after pretreatment of cultured bovine adrenal chromaffin cells with the phorbol ester 4B-phorbol 12-myristate 13-acetate (TPA) in the absence of added extracellular Ca2+. This effect of TPA was not reproduced when the secretagogues acetylcholine, nicotine, or veratrine were substituted for high K+. The implications of these results are discussed in relation to the role of protein kinase C in stimulus-secretion coupling in the chromaffin cell.


Adipokinetic hormone signaling in the malaria vector Anopheles gambiae facilitates Plasmodium falciparum sporogony.
An obligatory step in the complex life cycle of the malaria parasite is sporogony, which occurs during the oocyst stage in adult female Anopheles mosquitoes. Sporogony is metabolically demanding, and successful oocyst maturation is dependent on host lipids. In insects, lipid energy reserves are mobilized by adipokinetic hormones (AKHs). We hypothesized that Plasmodium falciparum infection activates Anopheles gambiae AKH signaling and lipid mobilization. We profiled the expression patterns of AKH pathway genes and AgAkh1 peptide levels in An. gambiae during starvation, after blood feeding, and following infection and observed a significant time-dependent up-regulation of AKH pathway genes and peptide levels during infection. Depletion of AgAkh1 and AgAkhR by RNAi reduced salivary gland sporozoite production, while synthetic AgAkh1 peptide supplementation rescued sporozoite numbers. Inoculation of uninfected female mosquitoes with supernatant from P. falciparum-infected midguts activated AKH signaling. Clearly, identifying the parasite molecules mediating AKH signaling in P. falciparum sporogony is paramount.


Accuracy of four intraoral scanners in oral implantology: a comparative in vitro study.
Until now, only a few studies have compared the ability of different intraoral scanners (IOS) to capture high-quality impressions in patients with dental implants. Hence, the aim of this study was to compare the trueness and precision of four IOS in a partially edentulous model (PEM) with three implants and in a fully edentulous model (FEM) with six implants. Two gypsum models were prepared with respectively three and six implant analogues, and polyether-ether-ketone cylinders screwed on. These models were scanned with a reference scanner (ScanRider®), and with four IOS (CS3600®, Trios3®, Omnicam®, TrueDefinition®); five scans were taken for each model, using each IOS. All IOS datasets were loaded into reverse-engineering software, where they were superimposed on the reference model, to evaluate trueness, and superimposed on each other within groups, to determine precision. A detailed statistical analysis was carried out. In the PEM, CS3600® had the best trueness (45.8 ± 1.6μm), followed by Trios3® (50.2 ± 2.5μm), Omnicam® (58.8 ± 1.6μm) and TrueDefinition® (61.4 ± 3.0μm). Significant differences were found between CS3600® and Trios3®, CS3600® and Omnicam®, CS3600® and TrueDefinition®, Trios3® and Omnicam®, Trios3® and TrueDefinition®. In the FEM, CS3600® had the best trueness (60.6 ± 11.7μm), followed by Omnicam® (66.4 ± 3.9μm), Trios3® (67.2 ± 6.9μm) and TrueDefinition® (106.4 ± 23.1μm). Significant differences were found between CS3600® and TrueDefinition®, Trios3® and TrueDefinition®, Omnicam® and TrueDefinition®. For all scanners, the trueness values obtained in the PEM were significantly better than those obtained in the FEM. In the PEM, TrueDefinition® had the best precision (19.5 ± 3.1μm), followed by Trios3® (24.5 ± 3.7μm), CS3600® (24.8 ± 4.6μm) and Omnicam® (26.3 ± 1.5μm); no statistically significant differences were found among different IOS. In the FEM, Trios3® had the best precision (31.5 ± 9.8μm), followed by Omnicam® (57.2 ± 9.1μm), CS3600® (65.5 ± 16.7μm) and TrueDefinition® (75.3 ± 43.8μm); no statistically significant differences were found among different IOS. For CS3600®, For CS3600®, Omnicam® and TrueDefinition®, the values obtained in the PEM were significantly better than those obtained in the FEM; no significant differences were found for Trios3®. Significant differences in trueness were found among different IOS; for each scanner, the trueness was higher in the PEM than in the FEM. Conversely, the IOS did not significantly differ in precision; for CS3600®, Omnicam® and TrueDefinition®, the precision was higher in the PEM than in the FEM. These findings may have important clinical implications.


[SHCS and the laboratory diagnosis of HIV infection--from the development of the HIV Western blot to virus quantification and clinically relevant individual virus characterization].
The first reliable diagnostic tools for the diagnosis of HIV infection, Western blot and ELISA, were created 20 years ago in the U.S., using initially sera from AIDS patients diagnosed clinically in Switzerland. In Swiss laboratories the diagnosis of HIV infection today is established by using 4th generation screening tests which detect both antibodies and p24 antigen while in the doctor's surgery a rapid antibody assay is used. Confirmation in authorized confirmatory labs relies on a set of different minimal combinations of positive test results derived from both the first and second blood specimen. In patients with a confirmed diagnosis of HIV infection, two further principal questions arise concerning, on the one hand, the virus load and, on the other hand, some clinically relevant properties of the infecting virus (type or subtype, resistance against antiretroviral drugs). The paper starts with a personal flashback to the first days of HIV diagnostics and describes the sensible use of tests available today for answering the above-mentioned principal questions. Alternative methods which can be used when standard tests fail or appear unreliable are mentioned also.


Susceptibility of protein synthesis to neomycin in neomycin-producing Streptomyces fradiae.
A cell-free protein-synthesizing system from Streptomyces fradiae was developed by preparing ribosomes and an S-150 fraction with precautions to prevent protease action. Using this system, the ribosomes of this organism were shown to be susceptible to its own product, neomycin.


Use of pre-operative calcium and vitamin D supplementation to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy: a systematic review.
This systematic review aimed to establish the evidence behind the use of pre-operative calcium, vitamin D or both calcium and vitamin D to prevent post-operative hypocalcaemia in patients undergoing thyroidectomy. This review included prospective clinical trials on adult human patients that were published in English and which studied the effects of pre-operative supplementation with calcium, vitamin D or both calcium and vitamin D on the rate of post-operative hypocalcaemia following total thyroidectomy. Seven out of the nine trials included reported statistically significantly reduced rates of post-operative laboratory hypocalcaemia (absolute risk reduction, 13-59 per cent) and symptomatic hypocalcaemia (absolute reduction, 11-40 per cent) following pre-operative supplementation. Pre-operative treatment with calcium, vitamin D or both calcium and vitamin D reduces the risk of post-operative hypocalcaemia and should be considered in patients undergoing total thyroidectomy.