Transperineal ultrasound assessment of fetal head elevation by maneuvers used for managing umbilical cord prolapse.
To assess objectively the degree of fetal head elevation achieved by different maneuvers commonly used for managing umbilical cord prolapse. This was a prospective observational study of pregnant women at term before elective Cesarean delivery. A baseline assessment of fetal head station was performed with the woman in the supine position, using transperineal ultrasound for measuring the parasagittal angle of progression (psAOP), head-symphysis distance (HSD) and head-perineum distance (HPD). The ultrasonographic measurements of fetal head station were repeated during different maneuvers, including elevation of the maternal buttocks using a wedge, knee-chest position, Trendelenburg position with a 15° tilt and filling the maternal urinary bladder with 100 mL, 300 mL and 500 mL of normal saline. The measurements obtained during the maneuvers were compared with the baseline measurements. Twenty pregnant women scheduled for elective Cesarean section at term were included in the study. When compared with baseline (median psAOP, 103.6°), the knee-chest position gave the strongest elevation effect, with the greatest reduction in psAOP (psAOP, 80.7°; P < 0.001), followed by filling the bladder with 500 mL (psAOP, 89.9°; P < 0.001) and 300 mL (psAOP, 94.4°; P < 0.001) of normal saline. Filling the maternal bladder with 100 mL of normal saline (psAOP, 96.1°; P = 0.001), the Trendelenburg position (psAOP, 96.8°; P = 0.014) and elevating the maternal buttocks (psAOP, 98.3°; P = 0.033) gave modest elevation effects. Similar findings were reported for HSD and HPD. The fetal head elevation effects of the knee-chest position, Trendelenburg position and elevation of the maternal buttocks were independent of the initial fetal head station, but that of bladder filling was greater when the initial head station was low. To elevate the fetal presenting part, the knee-chest position provides the best effect, followed by filling the maternal urinary bladder with 500 mL then 300 mL of fluid, respectively. Filling the bladder with 100 mL of fluid, the Trendelenburg position and elevation of the maternal buttocks have modest effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.


Nanohoneycomb Surface-Enhanced Raman Spectroscopy-Active Chip for the Determination of Biomarkers of Hepatocellular Carcinoma.
Overexpression of the Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) is an essential biomarker for early diagnosis of hepatocellular carcinoma (HCC). In this study, we designed a new surface-enhanced Raman spectroscopy active chip for the detection of AFP with high sensitivity and excellent repeatability. This chip was composed of a honeycomb gold nanostructure array with strong electromagnetic field coupling due to the special cavity geometric characteristics of the honeycomb structure. The honeycomb structure exhibited extraordinary performance for the specific detection of AFP in the range of 0.003-3 ng/mL and also determined the proportion of AFP-L3 with a high degree of accuracy, which has shown great potential for application in the clinical diagnosis of HCC.


Mass spectrometry characterization, antioxidant activity, and cytotoxicity of the peel and pulp extracts of Pitomba.
The fruit of the Talisia esculenta tree, is largely consumed and appreciated for its bittersweet taste; however, detailed information on its constituent bioactive compounds is still scarce. Therefore, this study aims to screen the antioxidant activity by six methods and determine the chemical profile of the pitomba fruit peel and pulp by electrospray ionization-Fourier transform-mass spectrometry. This is the first study attempting to identify the bioactive compounds in the pitomba fruit peel. Consequently, 19 and 14 compounds were identified in the ethanolic and hexanic peel extracts, while 7 and 10 compounds were detected in the ethanolic and hexanic pulp extracts, respectively. The common compounds across the board were citric acid, ascorbic acid, and shikimic acid. In addition, the ethanolic peel extract exhibited a high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (54.21-81.41%). The obtained results highlight the importance the pitomba fruit as a promising source of natural compounds with high antioxidant activities.


Measurement of bulk mechanical properties of tissue using laser speckle rheology.
In virtually all tissues, disease progression is accompanied by changes in the mechanical properties. Laser speckle rheology (LSR) is a new technique we have developed to measure the mechanical properties of tissue. By illuminating the sample with coherent laser light and calculating the speckle intensity modulations from reflected laser speckle patterns, LSR calculates τ, the decay time constant of intensity decorrelation which is closely associated with tissue mechanical properties. In this paper we validate the use of LSR technology in measuring mechanical properties of tissue. LSR measurements of τ are performed on a variety of phantom and tissue samples and compared with the complex shear modulus G*, measured using a rheometer. In all cases, strong correlation is observed between τ and G* (r=0.95, p < 0.002). These results demonstrate the efficacy of LSR as a non-invasive and non-contact technology for mechanical evaluation of biological samples.


Different forms of alkaline phosphatase in adult rat femur. Effect of a vitamin D3-deficient diet and of a sorbitol-enriched diet.
In the femoral extremities of the adult rat containing the metaphysis, the epiphyseal cartilage, and the epiphysis, four alkaline phosphatase (AP) forms were distinguished on polyacrylamide gel electrophoresis. Two soluble forms were present in the 160,000 g supernatant: one of Mr 165 kDa and another of Mr 110-115 kDa, which exhibited a strong catalytical activity. Moreover, from the pellet, three membrane-bound forms of Mr 130, 110-115, and 100 kDa could be extacted with sodium deoxycholate. When denaturated AP was visualized by postelectrophoretic autoradiography of the phosphorylated intermediates, subunits always appeared as three monomers of Mr 75-80, 60-70, and 50-60 kDa. As four native forms but only three types of subunits were found to be present in the femur, it seems that, apart from homodimers, some heterodimers could also occur. Three types of diets were administered to three groups of rats for 5 weeks. Two are known to disturb bone mineralization: (1) a vitamin D3-deficient diet, and (2) the same as (1) but enriched with 12% sorbitol. The third was a normal diet containing vitamin D3. Concerning the effects on AP of dietary sorbitol and the vitamin D3-deficient diet, it was found that rats receiving the diet supplemented with sorbitol showed a substantial rise in the activity of the Mr 165 kDa form with the concomitant appearance of a new monomer of Mr 100 kDa. In contrast, rats fed the vitamin D3-deficient diet always displayed an increase in enzyme activity, principally of the Mr 100 and 110 kDa forms.(ABSTRACT TRUNCATED AT 250 WORDS)


Long non-coding RNA GAS5 inhibited hepatitis C virus replication by binding viral NS3 protein.
HCV infection has a complex and dynamic process which involves a large number of viral and host factors. Long non-coding RNA GAS5 inhibits liver fibrosis and liver tumor migration and invasion. However, the contribution of GAS5 on HCV infection remains unknown. In this study, GAS5 was gradually upregulated during HCV infection in Huh7 cells. In addition, GAS5 attenuated virus replication with its 5' end sequences, as confirmed by different GAS5 truncations. Moreover, this 5' end sequences showed RNA-protein interaction with HCV NS3 protein that could act as a decoy to inhibit its functions, which contributed to the suppression of HCV replication. Finally, the innate immune responses remained low in HCV infected Huh7 cells, ruling out the possibility of GAS5 to modulate innate immunity. Thus, HCV stimulated endogenous GAS5 can suppress HCV infection by acting as HCV NS3 protein decoy, providing a potential role of GAS5 as a diagnostic or therapeutic target.


pyWitness 1.0: A python eyewitness identification analysis toolkit.
pyWitness is a python toolkit for recognition memory experiments, with a focus on eyewitness identification (ID) data analysis and model fitting. The current practice is for researchers to use different statistical packages to analyze a single dataset. pyWitness streamlines the process. In addition to conducting key data analyses (e.g., receiver operating characteristic analysis, confidence accuracy characteristic analysis), statistical comparisons, signal-detection-based model fits, simulated data generation, and power analyses are also possible. We describe the package implementation and provide detailed instructions and tutorials with datasets so that users can follow. There is also an online manual that is regularly updated. We developed pyWitness to be user-friendly, reduce human interaction with pre-processing and processing of data and model fits, and produce publication-ready plots. All pyWitness features align with open science practices, such that the algorithms, fits, and methods are reproducible and documented. While pyWitness is a python toolkit, it can also be used from R for users more accustomed to this environment.


Detection of equine arteritis virus by real-time TaqMan reverse transcription-PCR assay.
A one-tube real-time TaqMan reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for the detection of equine arteritis virus (EAV). The test was validated using the seminal plasma and nasal secretions of infected horses that were proven to contain EAV by traditional virus isolation in rabbit kidney thirteen (RK-13) cells, as well as a variety of cell culture-propagated European and North American strains of EAV. The primers and a fluorogenic TaqMan probe were designed to amplify and detect a highly conserved region of open reading frame 7 (ORF7) of EAV. The real-time TaqMan PCR assay detected EAV RNA in all samples that were confirmed to contain infectious EAV by virus isolation. The assay had an analytical sensitivity of 10 molecules of EAV RNA allowing the detection of EAV in clinical samples or tissue culture fluid (TCF) containing at least 200 viral RNA copies per ml. Thus, the one-tube real-time TaqMan RT-PCR assay provides a rapid, accurate, quantitative, convenient and high sample throughput system for diagnosis of EAV infection, in a closed-tube format that minimizes the risk of cross-contamination.


Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction.
To compare the efficacy and safety of low molecular weight heparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. Three-hundred patients receiving fibrinolytic therapy following acute myocardial infarction were randomly assigned to low molecular weight heparin as enoxaparin (40 mg intravenous bolus, then 40 mg subcutaneously every 8 h, n=149) or unfractionated heparin (5000 U intravenous bolus, then 30 000 U. 24 h(-1), adjusted to an activated partial thromboplastin time 2-2.5x normal, n=151) for 4 days in conjunction with routine therapy. Clinical and therapeutic variables were analysed, in addition to use of enoxaparin or unfractionated heparin, to determine independent predictors of the 90-day composite triple end-point (death, non-fatal reinfarction, or readmission with unstable angina). The triple end-point occurred more frequently in patients receiving unfractionated heparin rather than enoxaparin (36% vs. 26%; P=0.04). Logistic regression modelling of baseline and clinical variables identified the only independent risk factors for recurrent events as left ventricular failure, hypertension, and use of unfractionated heparin rather than enoxaparin. There was no difference in major haemorrhage between those receiving enoxaparin (3%) and unfractionated heparin (4%). Use of enoxaparin compared with unfractionated heparin in patients receiving fibrinolytic therapy for acute myocardial infarction was associated with fewer recurrent cardiac events at 90 days. This benefit was independent of other important clinical and therapeutic factors.


Structure-function studies of a novel laccase-like multicopper oxidase from Thermothelomyces thermophila provide insights into its biological role.
Multicopper oxidases are promiscuous biocatalysts with great potential for the production of industrial compounds. This study is focused on the elucidation of the structure-function determinants of a novel laccase-like multicopper oxidase from the thermophilic fungus Thermothelomyces thermophila (TtLMCO1), which is capable of oxidizing both ascorbic acid and phenolic compounds and thus is functionally categorized between the ascorbate oxidases and fungal ascomycete laccases (asco-laccases). The crystal structure of TtLMCO1, determined using an AlphaFold2 model due to a lack of experimentally determined structures of close homologues, revealed a three-domain laccase with two copper sites, lacking the C-terminal plug observed in other asco-laccases. Analysis of solvent tunnels highlighted the amino acids that are crucial for proton transfer into the trinuclear copper site. Docking simulations showed that the ability of TtLMCO1 to oxidize ortho-substituted phenols stems from the movement of two polar amino acids at the hydrophilic side of the substrate-binding region, providing structural evidence for the promiscuity of this enzyme.


Allele-specific expression is widespread in Bos indicus muscle and affects meat quality candidate genes.
Differences between the expression of the two alleles of a gene are known as allele-specific expression (ASE), a common event in the transcriptome of mammals. Despite ASE being a source of phenotypic variation, its occurrence and effects on genetic prediction of economically relevant traits are still unexplored in bovines. Furthermore, as ASE events are likely driven by cis-regulatory mutations, scanning them throughout the bovine genome represents a significant step to elucidate the mechanisms underlying gene expression regulation. To address this question in a Bos indicus population, we built the ASE profile of the skeletal muscle tissue of 190 Nelore steers, using RNA sequencing data and SNPs genotypes from the Illumina BovineHD BeadChip (770 K bp). After quality control, 820 SNPs showed at least one sample with ASE. These SNPs were widespread among all autosomal chromosomes, being 32.01% found in 3'UTR and 31.41% in coding regions. We observed a considerable variation of ASE profile among individuals, which highlighted the need for biological replicates in ASE studies. Functional analysis revealed that ASE genes play critical biological functions in the development and maintenance of muscle tissue. Additionally, some of these genes were previously reported as associated with beef production and quality traits in livestock, thus indicating a possible source of bias on genomic predictions for these traits.


A theoretical study of the Si-O bond in disiloxane and related molecules.
A comparison of semi-empirical (MNDO) and ab initio (GAUSSIAN) calculations for disiloxane and related molecules is given. The STO-3G* basis set well produced the observed geometries of disiloxane (less than SiOSi observed 144 degrees, calculated 140 degrees), dimethoxy-dimethylsilane (less than OSiO obsd tetrahedral, calc 102 degrees), methyl silyl ether (less than COSi obsd 121 degrees, calc 118 degrees) and correctly predicted the planar geometry found for cyclotrisiloxane. In contrast, more complex basis sets (3-21G(*), DZP, TZVP) gave much poorer agreement with the observed geometries. Comparison of the STO-3G* and the STO-3G basis sets demonstrates the necessity of including d-orbitals on the silicon. However, the semi-empirical MNDO program gave, despite the absence of d-orbitals, a better approximation to the molecular geometry than the complex ab initio basis sets. Force field parameters have been calculated for kSiOSi, kOSiO, 0.089 and 0.73 mdyneA/rad2, and the SiOSiO torsion which has a V1 potential of -0.68 kcal/mol. In addition, the HSiOH torsion is shown to have a three-fold potential of 0.78 kcal/mol. These are profoundly different from the analogous carbon-oxygen force constants, demonstrating that C-O parameters cannot be transferred to the corresponding Si-O systems.


[Giant cell tumor of soft tissues. Report of two cases].
We report two cases of giant-cell tumour of soft tissue (TCG-TM). The first case occurred in a 26-year-old woman presenting with a subcutaneous tumour of the left leg. Pathological study revealed a tumour comparable to benign giant cell tumour of bone. The patient is well without recurrence 10 months after the diagnosis. The second case concerned a 49-year-old man with a huge mass of the thigh. Microscopically, the tumour was composed of sheets of mononuclear and multinucleated cells. Mononuclear cells presented severe atypia and a high mitotic activity. Eighteen months later, the patient died with diffuse pulmonary metastases. TCG-TMs are uncommon and represent a distinct entity whose clinical behaviour and histological features are similar to giant-cell tumour of bone. The malignant variant is debatable. The differential diagnosis includes other tumours rich in osteoclast-like cells.


Complete Genome Sequence of Arthrobacter Phage ScienceWizSam.
Phage ScienceWizSam was isolated from soil using Arthrobacter sp. strain ATCC 21022. The phage genome is 58,217 bp with 96 open reading frames (ORFs). All of the ORFs are transcribed rightwards. Based on gene content similarity, ScienceWizSam is assigned to phage subcluster AU1.


Virion endocytosis is a major target for murid herpesvirus-4 neutralization.
Herpesviruses consistently transmit from immunocompetent carriers, implying that their neutralization is hard to achieve. Murid herpesvirus-4 (MuHV-4) exploits host IgG Fc receptors to bypass blocks to cell binding, and pH-dependent protein conformation changes to unveil its fusion machinery only after endocytosis. Nevertheless, neutralization remains possible by targeting the virion glycoprotein H (gH)-gL heterodimer, and the neutralizing antibody responses of MuHV-4 carriers are improved by boosting with recombinant gH-gL. We analysed here how gH-gL-directed neutralization works. The MuHV-4 gH-gL binds to heparan sulfate. However, most gH-gL-specific neutralizing antibodies did not block this interaction; neither did they act directly on fusion. Instead, they blocked virion endocytosis and transport to the late endosomes, where membrane fusion normally occurs. The poor endocytosis of gH-gL-neutralized virions was recapitulated precisely by virions genetically lacking gL. Therefore, driving virion uptake appears to be an important function of gH-gL that provides a major target for antibody-mediated neutralization.


Effects of renal dysfunction on cardiovascular events in diabetic patients with hypertension: challenge-DM Study subgroup analysis.
This study investigated the relation between renal dysfunction and cardiovascular events in patients from the Challenge-DM Study (a large-scale investigation of Japanese diabetic patients with hypertension on candesartan therapy). The subjects were 4706 patients in whom renal function could be assessed at the time of registration among 16860 patients analyzed in the Challenge-DM Study. The definition of renal dysfunction (low GFR) was an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) calculated by the formula for Japanese. The low GFR group was older, and had a high proportion of females and a high prevalence of cerebrovascular or cardiovascular disease (CVD) compared to the normal GFR group (eGFR ≥ 60 ml/min/1.73 m(2)). Univariate Cox regression analysis of cardiovascular events showed a significant increase in the incidence of primary events and total events in the low GFR group. Among patients <65 years old, the same results were obtained, but no differences were found between the low GFR and normal GFR groups aged over 65 years. Multivariate Cox regression analysis was done with patient characteristics at registration and the presence/absence of achieving the target blood pressure and HbA(1c) before the event as explanatory variables. As a result, low GFR was not the main cause of cardiovascular events, but it had a significant influence on primary events and total events among patients <65 years old. Low GFR may be an independent risk factor for cerebrovascular and CVD among young and middle-aged Japanese diabetic patients with hypertension on candesartan therapy.


In acromegalic patients the serum levels of interleukin-33 and Resolvin D1 influence skin perfusion of hands: A pilot study.
Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-I) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and D-series resolvins 1 (RvD1) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC). IL33 and RvD1 have been assessed in 20 AP and 20 HC. Nailfold videocapillaroscopy (NVC) was performed and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations. IL33 was significantly higher in AP compared to HC [73.08 pg/ml (IQR 47.11-100.80 pg/ml) vs 41.5 4 pg/ml (IQR 20.16-55.49 pg/ml), p < 0.05] and RvD1 was significantly lower in AP than HC [36.1 pg/ml (IQR 27.88-66.21 pg/ml) vs 60.01 pg/ml (IQR 46.88-74.69 pg/ml), p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [56.66 pU (IQR 46.29-65.44 pU) vs 87 pU (IQR 80-98 pU), p < 0.001]. The median values of ROI1 and ROI3 were significantly lower in AP compared to HC [112.81 pU (IQR 83.36-121.69 pU) vs 131 pU (IQR 108-135 pU), p < 0.05] and [59.78 pU (IQR 46.84-79.75 pU) vs 85 pU (IQR 78-98 pU), p < 0.05], respectively. The proximal-distal gradient (PDG) was observed in 8 of 20 (40 %) AP. Serum IL33 is higher in AP compared to HC; conversely, RvD1 is lower in AP compared to HC. Reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction.


[Patient-centered care. Improvement of communication between university medical centers and general practitioners for patients in neuro-oncology].
Communication between university medical centers and general practitioners (GP) is becoming increasingly more important in supportive patient care. A survey among GPs was performed with the primary objective to assess their opinion on current workflow and communication between GPs and the university medical center. The GPs were asked to score (grades 1-6) their opinion on the current interdisciplinary workflow in the care of patients with brain tumors, thereby rating communication between a university medical center in general and the neuro-oncology outpatient center in particular. Questionnaires were sent to1000 GPs and the response rate was 15 %. The mean scored evaluation of the university medical center in general was 2.62 and of the neuro-oncological outpatient clinic 2.28 (range 1-6). The most often mentioned issues to be improved were easier/early telephone information (44 %) and a constantly available contact person (49 %). Interestingly, > 60 % of the GPs indicated they would support web-based tumor boards for interdisciplinary and palliative neuro-oncological care. As interdisciplinary care for neuro-oncology patients is an essential part of therapy, improvement of communication between GPs and university medical centers is indispensable. Integrating currently available electronic platforms under data protection aspects into neuro-oncological palliative care could be an interesting tool in order to establish healthcare networks and could find acceptance with GPs.


Comparative measurement of the molecular weight of an antineoplastic glucan from BCG vaccine.
Bacillus Calmette-Guérin (BCG) vaccine, developed originally for the prophylaxis of tuberculosis, is a potent immunostimulant used to treat superficial bladder carcinoma in man. The aim of this study was to compare the molecular weight and self-association properties of an antineoplastic glucan (PS1A1) extracted from BCG vaccine as determined by different techniques including diffusion, light-scattering and chromatographic methods. In the diffusion experiments, a semi-empirical relationship was derived between the effective diffusion coefficients, Dp, and the weight-average molecular weights, Mw, of several dextrans used as standards, according to the equation Dp = 2.233 x 10(-6) x Mw(-0.66). On the basis of this relationship, the molecular weight of PS1A1 was found to be 57.4 kDa, although, unexpectedly, membrane association was high, most probably because of molecular branching. In the light-scattering experiment it was observed that, unlike dextran, PS1A1 undergoes concentration-dependent multimerization in water. However, the molecular weight of PS1A1 in 0.1 M sodium chloride ranged from 60 to 68 kDa, with a mean of 65 kDa, over the same concentration range. This value was in agreement with the molecular weight determined for PS1A1 by gel-filtration chromatography in previous studies, suggesting that 65 kDa represents the approximate monomeric size of the unassociated molecule. Thus, it was evident that the aggregation was suppressed by electrolyte. Elemental analysis by X-ray fluorescence showed that PS1A1 contained carbon, oxygen, hydrogen and phosphorus, indicating that hitherto unobserved ionized phosphate groups might promote electrostatic interactions.


Androgen receptor gene mutations in human prostate cancer.
To investigate the structural abnormality of the androgen receptor (AR) in human prostate cancers, exons B-H encoding DNA- and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products using originally designed oligoprimers. Tissues from 7 cases of untreated stage B prostate cancer surgically removed and from 8 cases of endocrine therapy-resistant cancers obtained at autopsy were used in the study. Two different mutations were identified in exons D and H in the different cancer foci of the same cancer death patient. One mutation in exon D (at codon 701, Leu to His) was detected in the prostate, and the other in exon H (at codon 877, Thr to Ala) was found in metastatic tissues. In untreated cancer tissues and the other autopsy samples, no mutations were detected. The mutation in exon H was identical to that reported in LNCaP cells. These results indicate that AR gene mutations occur in relation to endocrine therapy-resistance, although the mutation was found in 1 out of 8 resistant cases (12.5%) at autopsy.


Interaction of Dehydrogenase Enzymes with Nanoparticles in Industrial and Medical Applications, and the Associated Challenges: A Mini-review.
Nanoparticles (NPs) are a group of particles with at least one dimension ranging from 1 nm to 100 nm in diameter and a surrounding interfacial layer. The NP-protein interactions include covalent and non-covalent bonds. Several dehydrogenase enzymes (e.g., alcohol dehydrogenase, lactate dehydrogenase, alanine dehydrogenase, glutamate dehydrogenase, leucine dehydrogenase, phenylalanine dehydrogenase, and malate dehydrogenase) are used for immobilization by NPs. Also, magnetic NPs and quantum dots are promising model systems for the design of bioanalytical sensors and biological enzyme assemblies. In this overview, we aimed to improve the current knowledge of interactions between dehydrogenase enzymes and NPs and to introduce dehydrogenases with industrial and medical applications. Also, bioconjugation of NPs with dehydrogenase enzymes has broad applications in biocatalysis and nanomedicine in the field of drug discovery. However, studies on the characterization of NP-enzyme complexes show that the anatomy and activity of enzymes are dependent on the chemistry of NP ligands, NP size, and labeling methods. Moreover, the NPprotein conjugates show increased/decreased enzymatic activities, depending on the NP features. In this study, we reviewed the findings related to NP-enzyme interactions for nanotechnology applications and conjugation techniques. We also highlighted several challenges associated with the NP-enzyme interactions, including the stability and reusability of enzymes in NP-enzyme formation.


Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.
The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (-4.1 points) than placebo + haloperidol (-2.3 points) (mean difference, -1.9 points [95% CI, -2.8 to -0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, -1.0 mg [95% CI, -2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%]). In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects. clinicaltrials.gov Identifier: NCT01949662.


Pediatric approach to prevention of coronary heart disease.
Management of children with hypercholesterolemia has proven to be a controversial issue. The appropriate approach is to test those at highest risk for premature coronary heart disease most likely to benefit from intervention. Recommendations are reviewed in the context of the National Cholesterol Education Program Expert Panel on Blood Cholesterol Levels in Children and Adolescents. An overview is provided of the problem of preventing coronary heart disease through childhood intervention.


Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells.
Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host. In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2-related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors. These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway.


Contemporary Anesthetic Evaluation and Management for Electroconvulsive Therapy.
Electroconvulsive therapy (ECT) is a medical treatment most often used in patients with severe major depression that has not responded to other treatments. ECT is also indicated for patients with other severe psychiatric conditions, including bipolar disorder, schizophrenia, schizoaffective disorders, catatonia, and neuroleptic malignant syndrome. Contemporary "modified ECT" involves inducing general anesthesia with neuromuscular blockade before inducing the therapeutic seizure. The goal of this review is to combine an evidence-based update with the experience of the author's institution to provide a practical approach to anesthetic care for the patient undergoing ECT.


Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF.
Drug-resistance to chemotherapics in aggressive neuroblastoma (NB) is characterized by enhanced cell survival mediated by TrkB and its ligand, brain-derived neurotrophic factor (BDNF); thus reduction in BDNF levels represent a promising strategy to overcome drug-resistance, but how chemotherapics regulate BDNF is unknown. Here, cisplatin treatment in SK-N-BE neuroblastoma upregulated multiple BDNF transcripts, except exons 5 and 8 variants. Cisplatin increased BDNF mRNA and protein, and enhanced translation of a firefly reporter gene flanked by BDNF 5'UTR exons 1, 2c, 4 or 6 and 3'UTR-long. To block BDNF translation we focused on aurora kinases inhibitors which are proposed as new chemotherapeutics. NB cell survival after 24 h treatment was 43% with cisplatin, and 22% by cisplatin+aurora kinase inhibitor PHA-680632, while the aurora kinases inhibitor alone was less effective; however the combined treatment induced a paradoxical increase of BDNF in surviving cells with strong translational activation of exon6-3'UTR-long transcript, while translation of BDNF transcripts 1, 2C and 4 was suppressed. In conclusion, combined cisplatin and aurora kinase inhibitor treatment increases cell death, but induces BDNF overproduction in surviving cells through an aurora kinase-independent mechanism.


Effect of various polyamine analogs on in vitro polypeptide synthesis.
Various polyamine analogs were examined for their ability to stimulate and to function as sparing agents for the Mg2+ requirement in polypeptide synthesis at various temperatures in Escherichia coli (37 and 47 degrees C) and the extremely thermophilic Thermus thermophilus (60 and 70 degrees C) cell-free systems. The optimal concentration of each polyamine analog increased as the incubation temperature was elevated. At a fixed temperature, the optimal concentration of polyamine analogs was in the order diamines greater than triamines greater than tetraamines greater than pentaamines. All diamines tested stimulated polypeptide synthesis almost equally but lowered the optimal Mg2+ concentration in the order diaminopropane greater than putrescine greater than cadaverine. The degree of diamine stimulation was maximal at 37 degrees C. The effects of three triamines were very similar in the E. coli system but in the T. thermophilus system spermidine was most effective in stimulation of polypeptide synthesis. From the results of experiments using tetraamines and pentaamines, it was deduced that the presence of both aminobutyl and aminopropyl groups in polyamine analogs is important for stimulation of polypeptide synthesis. In the E. coli system, triamines were the most effective polyamines for stimulation of polyphenylalanine synthesis at both 37 and 47 degrees C, while, in the T. thermophilus system, thermospermine, a tetraamine, was most effective at 60 degrees C and 3,4,4,3-pentaamine was most effective at 70 degrees C.


Relationship between mild traumatic brain injury and the gut microbiome: A scoping review.
There is increasing evidence for the important role of gut microbiota (GMB) in the development and progression of neurologic pathologies. Some studies have shown that modifying the microbiome profile can confer benefits to patients. Mild traumatic brain injury (mTBI) is a common occurrence in the general population. Although most patients recover, in a minority, disabling symptoms can persist for several months. We carried out a review of the literature to assess the effect of mTBI on GMB and to determine whether alleviating dysbiosis can improve clinical outcomes in mTBI patients. We performed searches in Medline/PubMed and Embase using the keywords "MTBI" AND "microbiome" OR "microbiota". Additional articles were identified by manual searches and using the Google search engine. In animal models, a clear perturbation of GMB was reported following TBI and probiotic supplementation (Lactobacillus acidophilus or Clostridium butyricum) improved neurologic function. There were no studies on changes in GMB after mTBI in humans; however, pre- or probiotic supplementation reduced the infection rate in patients with severe TBI and shortened the time spent in the intensive care unit without conferring any neurologic benefits. Thus, although the findings from animal models are promising, clinical studies are needed to determine whether therapeutic strategies that restore gut microbiome profile can improve long-term outcomes of patients with mTBI.


Relations between anthropometric characteristics and degree of severity of the climacteric syndrome in Austrian women.
The connection between body-shape characteristics, namely distribution of subcutaneous fat, and the occurrence of psychic and somatic climacteric symptoms was investigated in 142 postmenopausal women from Eastern Austria. It was found that both psychic and somatic symptoms are significantly related to body-shape characteristics. With increasing breadth and circumference, i.e. a higher proportion of subcutaneous fat, the degree of severity of several symptoms increases, with the exception of hot flushes and sweating, dizziness, headache and palpitation. Since, in the climacteric, subcutaneous fat has a positive impact on the secretion of oestrogens and thus on climacteric symptoms, the results of the present study may be interpreted as an effect of the psychosocial stress to which corpulent women are exposed in our society because they do not fit the beauty ideal typical of our culture.


Toxicological effects of chlorophenols to green algae observed at various pH and concentration of humic acid.
Humic acid (HA) is ubiquitous organic matter derived by microbial metabolisms. This polymeric substance has both hydrophilic and hydrophobic moieties, and it is known that they affect to bioavailability of environmental pollutants. Objective of this study is to investigate the toxicological effects of chlorophenols to green algae observed at various pH and concentration of HA. Toxicity was determined by algal growth inhibition rate and EC50 of green algae Chlorella vulgaris. As a result, toxicity of 2,4-dichlorophenol was mitigated with increase of the coexisting amount of HA and solution pH. In the case of coexisting 2.5 ppm HA, EC50 of 2,4-dichlorophenol was 12.2 ppm and approximately three times higher than the case of absence of HA at pH 7.5. Meanwhile, Toxicity of 2,4,6-trichlorophenol was enhanced with increase of the coexisting amount of HA. In the case of absence of HA, EC50 of 2,4,6-trichlorophenol was 13.1 ppm and approximately two times higher than the case of coexisting 2.5 ppm HA at pH 7.5. Results suggested that toxicity of chlorophenols is influenced by the electrostatic and hydrophobic interaction between HA and chlorophenols. The hypothesis of toxicity enhancement pathway was proposed in the case of equilibrium-state 2,4,6-trichlorophenol between anionic and nonionic states.


Multidisciplinary approach as the optimum for surgical treatment of retroperitoneal sarcomas in women.
The study aimed at evaluating surgical treatment results of retroperitoneal sarcomas (RPS) in female patients in terms of urological and oncological-gynecological collaboration. The authors performed a retrospective review of 17 women who underwent resection of a retroperitoneal tumor. The surgical results, complications, and both overall and disease-free survivals were evaluated. The assessment of a positive surgical margin and the size of the tumor were the second objective. The Kaplan-Meyer survival analysis was used for statistical evaluation. The median follow-up was 60 (26 - 128) months. The mean age was 55.4 (35 - 75) years. The mean size of tumors was 14.8 (6 - 45) cm. Local recurrences were recorded in three patients, while distal metastases were reported in one patient. Two patients died of distal metastases. The overall and cancer-specific survival was 87.5% and disease-free survival was 76.5%. Complete resection is the only effective treatment of retroperitoneal sarcomas. Presence of positive surgical margin is connected with a high risk of local recurrence regardless of an adjuvant chemo-and radiotherapy. The size of tumor had no impact on the survival or risk of local recurrence in the study group. The uro-gynecological collaboration was evaluated as well-suited in this part of oncological surgery.


Investigating the interactions of amino acid components on a mannitol-based spray-dried powder formulation for pulmonary delivery: A design of experiment approach.
Combining an amino acid and a sugar is a known strategy in the formulation of spray or freeze dried biomolecule powder formulations. The effect of the amino acid leucine in enhancing performance of spray-dried powders has been previously demonstrated, but interaction effects of several constituents which may provide multiple benefits, are less well-understood. A 3 factor 2 level (2(3)) factorial design was used to study the effects of leucine, glycine and alanine in a mannitol-based dry powder formulation on particle size, aerosolisation, emitted dose and cohesion. Other qualitative tests including scanning electronic microscopy and X-ray powder diffraction were also conducted on the design of experiment (DoE) trials. The results show that the use of glycine and/or alanine, though structurally related to leucine, did not achieve similar aerosol performance enhancing effects, rather the particle formation was hindered. However, when used in appropriate concentrations with leucine, the combination of amino acids produced an enhanced performance regardless of the presence of glycine and/or alanine, yielding significantly modified particle properties. The results from the DoE analyses also revealed the lack of linearity of effects for certain responses with a significant curvature in the model which would otherwise not be discovered using a trial-and-error approach.


Studies on the mechanism of callus cartilage differentiation and calcification during fracture healing.
The morphologic and biochemical events during fracture callus cartilage differentiation and calcification are presented. 1. Histologic studies have demonstrated that unimmobilized fractures heal through endochondral ossification. 2. Biochemical studies have demonstrated an increase in the activities of alkaline phosphatase, enzymes involved with aerobic glucose metabolism, and lysosomal enzymes and a decrease in activities of enzymes involved with glycogen synthesis and anaerobic glycolysis. Hexosamines and hydroxyproline show a net decrease with cartilage differentiation. 3. Electron microscopic studies have demonstrated the intracellular origin and aggregation of collagen molecules, the cellular origin of matrix vesicles, and the early sites of calcification in the fracture callus.


Validation of a simple mechanical accelerometer (pedometer) for the estimation of walking activity.
A small (28 g) mechanical accelerometer has been tested by subjecting it to controlled bench tests consisting of repetitive vertical oscillations on two designs of test rig. The accelerometer's 3-digit display provided a cumulated score with a maximum of 99.9 units. This score was compared with an independent count of the imposed oscillations and found to be linear with time (r = 0.996) and reproducible on retest (coefficient of variation = +/- 1.5%). The sensitivity ranged from 6.2 to 7.4 units/10,000 oscillations. The response was related to the maximal applied acceleration (calculated from the amplitude and frequency of the oscillations on the assumption that they were sinusoidal) and independent of the amplitude and frequency used. The threshold maximal acceleration was less than 2 m s-2 and the response had reached a plateau at 4 m s-2. During field studies the accelerometer was firmly attached over the hip in a waistband where it responded to the vertical accelerations produced by walking. When compared with an independent count of footsteps from a heel-mounted resistance pad the accelerometer score (after calibration) was not significantly different. The mean difference was (0.29 +/- 0.67, S.D.) 10(3) "steps" in a younger group (n = 8, mean age 39 years) and (0.46 +/- 1.08, S.D.) 10(3) "steps" in an older group of women (n = 6, mean age 65 years). Scores of around 10 X 10(3) "steps" can be expected in a day in moderately active young subjects and 40 X 10(3) "steps" in a week in the elderly. Simultaneously recorded scores from both right and left hips wee not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)


Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 100 patients using a prolonged phototest protocol.
There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24-83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity. To investigate the photoreactivity of patients with various subtypes of LE using an individualized phototest protocol. The results of phototests were correlated with the history of photosensitivity, the subtype of LE, the presence of autoantibodies and the use of anti-inflammatory medication by these patients. Phototesting with UVA, UVB and visible light was performed in 100 patients with LE. The diagnosis of LE was established both on clinical examination and skin histology. Serological studies were also performed in all patients. The phototests were performed on large skin areas of the forearm or trunk; the first dose was twice the minimal erythema dose and the dosage was increased according to the individual reactions of the patients at the test sites. Follow-up of skin reactions at the test sites was performed for up to 2 months. Histological examination of the photoprovoked skin lesions was carried out in 57 patients. Of the 100 patients included (81 women and 19 men; mean age 41 years, range 17-79), 46 had chronic discoid LE, 30 SCLE and 24 systemic LE. An abnormal reaction to UVR and visible light was found in 93% of our patients with LE. No clinical or histological evidence at the phototest sites of polymorphic light eruption was found. There was no correlation between photosensitivity and LE subtype, presence of autoantibodies or medical history. Concomitant use of anti-inflammatory medication seemed to exert only minimal influence on the results of phototesting. When using an extended phototesting protocol, almost all patients with LE in this study showed clinical and histological evidence of aberrant photosensitivity. Therefore, patients with LE should receive thorough advice and instruction on photoprotective measures, regardless of their history, LE subtype or presence of autoantibodies.


Feasibility of Speech Testing Using Wireless Connection in Single-Sided Cochlear Implant Users.
The speech tests used to evaluate language performance in patients with bilateral deafness (BiD) and cochlear implant (CI) are problematic if applied to patients with single-sided deafness (SSD) because normal ear hearing should be excluded. Thus, we investigated the feasibility of using wireless connection to evaluate speech intelligibility of the CI ear in patients with SSD. Subjects and. Patients with BiD and SSD were administered the word recognition scores (WRS) and speech intelligibility tests using an iPadbased wireless connection and conventional methods. To exclude normal side hearing in patients with SSD, masking noise and "plugged and muffed" method were used in the WRS and speech intelligibility tests, respectively. In patients with BiD, the WRS and speech intelligibility tests results using wireless connection and conventional methods were similar. In patients with SSD, the WRS using masking noise in the normal hearing ear was similar to that of using wireless connection. However, 3 of 11 patients with SSD showed under-masked results if using the "plugged and muffed" method. Speech intelligibility testing using wireless connection is a convenient and reliable method for evaluating CI performance in patients with SSD. The "plugged and muffed" method is not recommended for evaluating CI performance in patients with SSD.


Selective potentiation of N-methyl-D-aspartate-induced current by protein kinase C in Xenopus oocytes injected with rat brain RNA.
Glutamate receptors and protein kinase C (PKC) may play significant roles in long-term potentiation in hippocampus. To clarify the regulatory involvement of PKC in the functions of glutamate receptors, we examined the effects of PKC activation on current response induced by the activation of each subtype of glutamate receptor in Xenopus oocytes injected with rat brain RNA. Treatment with the PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), potentiated N-methyl-D-aspartate (NMDA)-induced current by about 2.5-fold, although it did not affect kainate-induced current at all. Quisqualate-mediated oscillatory current was almost abolished by this treatment. The TPA-induced potentiation of NMDA current was suppressed by staurosporine, an inhibitor of protein kinases. Pretreatment with 4-O-methyl-TPA, an inactive phorbol ester, had no effect on NMDA current. Current response mediated by NMDA receptors would thus appear to be modulated by PKC.


Assessment of tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption.
This prospective cross-sectional study aimed to investigate the potential association between primary-adult lactose malabsorption, fructose malabsorption, tryptophan (TRP) metabolism and the presence of depressive signs. Overall 251 patients, who were referred for lactase gene C/T-13910 polymorphism genotyping and fructose hydrogen/methane breath testing, were included. All participants filled out the Beck Depression Inventory (BDI II). Serum concentrations of tryptophan (TRP), kynurenine (KYN), kynuric acid (KYNA), and TRP competing amino acids (leucine, isoleucine, valine, phenylalanine, tyrosine) were measured by high-pressure liquid-chromatography. Logistic regression analysis was performed with lactose malabsorption, fructose malabsorption and all potential biomarkers of TRP metabolism to assess the effect on signs of depression, defined as a BDI II score > 13. Primary-adult lactose malabsorption and fructose malabsorption was detected in 65 (25.90%) and 65 (25.90%) patients, respectively. Fructose malabsorption was significantly associated with BDI II score, whereas no such relationship was found for lactose malabsorption. Serum levels of TRP and TRP metabolites were no predictors of depression. The authors suggest to conduct further prospective longitudinal studies in order to get further insight of associations between carbohydrate malabsorption, biomarkers and mood disorders.


Topographic mapping of EEG and evoked potentials in psychiatry: delusions, illusions, and realities.
This paper reviews the utility of topographic mapping of EEG and evoked potentials in psychiatry. Further, a wide variety of caveats related to this technique are reviewed including cerebral and extracerebral sources of artifact. Moreover, both questionable and legitimate uses of mapping in psychiatry are addressed and possible future applications of this technique are considered. Finally, multidisciplinary approaches to the study of the brain are discussed.


Effects of stimulation of nitric oxide synthesis on large artery stiffness in patients with peripheral arterial disease.
The role of endothelium-derived nitric oxide (NO) in modulation of large artery stiffness in patients with peripheral arterial disease (PAD) is unexplored. The aim of this study was to evaluate, using pulse wave analysis (PWA), changes in aortic and systemic arterial stiffness following administration of nitroglycerin and beta(2)-agonist salbutamol in PAD patients (n = 24) and in healthy controls (n = 24). Changes in estimated aortic pulse wave velocity (T(r)) and in augmentation index (AIx), following administration of nitroglycerin and salbutamol, were assessed using PWA. Salbutamol-induced changes in T(r) and in AIx were significantly reduced in PAD patients (P < 0.001 and < 0.001, respectively), while nitroglycerin-produced changes were not different (P = 0.25 and 0.35, respectively). Changes in T(r) after salbutamol administration were independent of changes in mean arterial pressure (MAP) (R = -0.21, P = 0.16). This study shows that stimulation of NO synthesis fails to modify stiffness of the large arteries in PAD patients and changes in aortic stiffness are independent of changes in MAP. Our data support the utility of PWA as a non-invasive method for assessment of NO-mediated vascular changes.


[Order of twins--random choice of natural selection?].
Testing of hypothesis that the order of twins is random. Confrontation of birthweight and incidence of stillbirth between twins. The group of 829 twin deliveries was investigated. Probability of distribution was assessed according to Bernoullie's trials schema. The first twin was usually heavier then the second one (p = 0.05), especially at term. Order of twin delivery was influenced by a birthweight difference > 250 g. In cases of single twin intrauterine death, the alive, term baby was delivered as the first one statistically more common (p = 0.029), despite of smaller number of cases. Discussion suggests that differences between twins are rather reasons of observed order than results. Hypothesis of natural selection of stronger baby for the first delivery was presented.


Importance of highly selective LC-MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen.
The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC-MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677-1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples.


Immune tolerance of skin allograft transplantation induced by immature dendritic cells of a third party carrying donor antigens in mice.
Dendritic cells (DCs) are the most powerful antigen-presenting cells in the body. Immature DCs (imDCs) can induce transplantation tolerance. In this study, using a mouse model of skin transplantation. We explored the antigen uptake by imDCs, changes in phenotype and function after antigen loading, as well as survival of skin grafts. Mononuclear cells from C57BL/6 mice mixed with a tritiated leucine ([(3)H]Leu) antigen supernate were incubated with Kunming mice imDC and mature DCs. We recorded the expressions of surface molecules that were detected using flow cytometry, mixed lymphocyte reactions, mean survival times, and postoperative morphological changes in skin grafts. After the addition of allogeneic antigen supernate, the counts per minute of imDCs were significantly higher than those of mature DCs. The expression rates of I(A)/I(E) and CD80 significantly increased on the cell surface of imDCs. The counts per minute of imDCs in mixed lymphocyte reactions in the presence of allogeneic antigens was significantly higher than those of controls. Comparing mean survival times with controls, skin grafts were significantly longer in the imDCs groups from donors or from a third party carrying donor antigens. ImDCs display a strong antigen uptake, gradually maturing in terms of phenotype and function after loading. Complementary application of cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin blocks the immune response of imDCs. Both imDCs from the third party carrying donor antigens and those from the donor strain can establish antigen-specific immune tolerance to allogeneic skin grafts.


Machine learning-guided the fabrication of nanozyme based on highly-stable violet phosphorene decorated with phosphorus-doped hierarchically porous carbon microsphere for portable intelligent sensing of mycophenolic acid in silage.
Violet phosphorene (VP) have been proved to be more stable than black phosphorene, but few reports for its application in electrochemical sensors. In this study, a highly-stable VP decorated with phosphorus-doped hierarchically porous carbon microsphere (PCM) with multiple enzyme-like activities as a nanozyme sensing platform for portable intelligent analysis of mycophenolic acid (MPA) in silage with machine learning (ML) assistance is successfully fabricated. The pore size distribution on the PCM surface is discussed using N2 adsorption tests, and morphological characterization indicates that the PCM is embedded in the layers of lamellar VP. The affinity of the VP-PCM nanozyme obtained under the guidance of the ML model reaches Km = 12.4 μmol/L for MPA. The VP-PCM/SPCE for the efficient detection of MPA exhibits high sensitivity, a wide detection range of 2.49 μmol/L - 71.14 μmol/L with a low limit of detection of 18.7 nmol/L. The proposed ML model with high prediction accuracy (R2 = 0.9999, MAPEP = 0.0081) assists the nanozyme sensor for intelligent and rapid quantification of MPA residues in corn silage and wheat silage with satisfactory recoveries of 93.33%-102.33%. The excellent biomimetic sensing properties of the VP-PCM nanozyme are driving the development of a novel MPA analysis strategy assisted by ML in the context of production requirements of livestock safety.


Evolution of cooperation with similarity to an archetype.
We use the framework of Colman with a Prisoner's Dilemma game and an evolutionary agent-based algorithm in order to study the evolution of cooperation and discrimination. We assume that players can discriminate on the basis of the phenotypic distance to an archetype, linked itself with a given behaviour in the game. However, we do not impose that the archetype corresponds to a conditionally cooperative behaviour. We show that cooperation can become the norm and discrimination can evolve spontaneously with no other assumption. For some archetypes, cooperation can even evolve faster and with more intensity than in the similarity-based case studied in Colman et al., 2012.


A highly selective sandwich-type FRET assay for ATP detection based on silica coated photon upconverting nanoparticles and split aptamer.
In this paper, we report a highly selective sandwich-type fluorescence resonance energy transfer (FRET) assay for ATP detection by combining the unique optical properties of silica coated photon upconverting NaYF4:Yb(3+), Er(3+) nanoparticles (Si@UCNPs) with the high specific recognition ability of ATP aptamer. In the protocol, a single aptamer of ATP was split into two fragments. One of which was covalently attached to the Si@UCNPs at the 5' end, and the other was labeled with Black Hole Quencher-1 (BHQ1) at the 3' end. In the presence of ATP, the two fragments bound ATP with high affinity to form the sandwich complexes on the surface of Si@UCNPs. ATP induced association of the two fragments, thus bringing the Si@UCNPs and BHQ1 into close proximity. Under the illumination of 980 nm laser, energy transfer took place between the Si@UCNPs as the donor and BHQ1 as the acceptor, creating an optical "sandwich-type" assay for ATP detection. By monitoring the fluorescence change of the Si@UCNPs at 550 nm, the presence of the ATP could be quantitatively detected with a detection limit of 1.70 μM. The linear response range was 2 μM-16 μM. The background of this assay was ignorable because the fluorescence intensity of Si@UCNPs at 550 nm was not changed in the absence of ATP. This assay was also able to discriminate ATP from its analogs.


Effectiveness of mitoxantrone on the proliferation of cell cultures derived from malignant mesenchymal tumors of human origin.
The antiproliferative potency of mitoxantrone (MITOX) has predominantly been established for epithelial and hematologic neoplasias. In this study the effectiveness of MITOX was investigated in vitro for 6 sarcomatous human cell lines derived from 2 synovial sarcomas, a malignant schwannoma, a malignant histiocytoma, a leiomyosarcoma, and a chondrosarcoma. The examination was performed using a proliferation assay with monolayer cell cultures. The effect of MITOX was compared with that of adriamycin (ADR) and cisplatin (CDDP). For each drug at least 3 concentrations were tested which covered the therapeutically achievable range, i.e., for MITOX 0.2-0.002 micrograms/ml, for ADR 0.5-0.005 micrograms/ml, and for CDDP 5.0-0.05 micrograms/ml. Test incubations were performed for 3 days. Antiproliferative potency of the cytostatic drugs was assessed by counting the number of cells at the start and the end of the test period with and without drug addition. Furthermore the dose inhibiting cell growth to 50% of controls (ID50) was determined for MITOX. For comparison 4 cell lines from carcinomatous lesions were included in the study. MITOX inhibited proliferation rates of 4 sarcomatous tumor cell lines more intensively than ADR, and was less effective in 2 cell lines. However, these differences were not significant. In all mesenchymal cell lines tested the antiproliferative potency of MITOX was more pronounced than that of CDDP. In carcinomatous cell lines the MITOX-induced growth inhibition was similar to that found in response to administration of ADR and CDDP confirming the described effect on epithelial tumors. The study suggests that MITOX possesses a growth inhibitory potency for malignant soft tissue tumors in vitro. From these data it may be worthwhile to initiate clinical trials testing the treatment of sarcomatous lesions with MITOX.


Identifying QT prolongation from ECG impressions using a general-purpose Natural Language Processor.
Typically detected via electrocardiograms (ECGs), QT interval prolongation is a known risk factor for sudden cardiac death. Since medications can promote or exacerbate the condition, detection of QT interval prolongation is important for clinical decision support. We investigated the accuracy of natural language processing (NLP) for identifying QT prolongation from cardiologist-generated, free-text ECG impressions compared to corrected QT (QTc) thresholds reported by ECG machines. After integrating negation detection to a locally developed natural language processor, the KnowledgeMap concept identifier, we evaluated NLP-based detection of QT prolongation compared to the calculated QTc on a set of 44,318 ECGs obtained from hospitalized patients. We also created a string query using regular expressions to identify QT prolongation. We calculated sensitivity and specificity of the methods using manual physician review of the cardiologist-generated reports as the gold standard. To investigate causes of "false positive" calculated QTc, we manually reviewed randomly selected ECGs with a long calculated QTc but no mention of QT prolongation. Separately, we validated the performance of the negation detection algorithm on 5000 manually categorized ECG phrases for any medical concept (not limited to QT prolongation) prior to developing the NLP query for QT prolongation. The NLP query for QT prolongation correctly identified 2364 of 2373 ECGs with QT prolongation with a sensitivity of 0.996 and a positive predictive value of 1.000. There were no false positives. The regular expression query had a sensitivity of 0.999 and positive predictive value of 0.982. In contrast, the positive predictive value of common QTc thresholds derived from ECG machines was 0.07-0.25 with corresponding sensitivities of 0.994-0.046. The negation detection algorithm had a recall of 0.973 and precision of 0.982 for 10,490 concepts found within ECG impressions. NLP and regular expression queries of cardiologists' ECG interpretations can more effectively identify QT prolongation than the automated QTc intervals reported by ECG machines. Future clinical decision support could employ NLP queries to detect QTc prolongation and other reported ECG abnormalities.


Expression cloning of TGF-beta receptors.
Using a powerful expression cloning method in COS cells, we have cloned the TGF-beta types II and III receptors. The type III TGF-beta receptor is a membrane-bound proteoglycan with a core protein of about 110 kDa. Stable expression of the type III receptor in L6 myoblasts leads to an apparent increase in the ability of the type II receptor to bind iodinated TGF-beta 1. The cloned type II receptor has a predicted protein core of about 60 kDa with a cysteine-rich extracellular domain, a single transmembrane domain, and a functional serine/threonine kinase domain that is homologous to the activin receptor and to the C. elegans protein daf-1. These results implicate serine/threonine phosphorylation as an important mechanism of TGF-beta action.


[Comparative study of applying tiaoxue yisui recipe and SSL regimen in treating infantile chronic aplastic anemia and analysis of its therapeutical mechanism].
To explore the effective method in treating infantile chronic aplastic anemia (ICAA) by using traditional Chinese medicine (TCM). Seventy-eight cases of ICAA were observed, 48 of them were treated with Tiaoxue Yisui recipe (treated group), 30 cases were treated with SSL regimen (control group). The remission rate and total effective rate in treated group were 52.08% and 81.25% respectively, they were higher than those in control group (P < 0.05). After one year treatment the ratio of hemopoietic and non-hemopoietic cells in treated group was higher than that in control group (P < 0.05). The number of megakaryocyte in treated group was more than those in control group (P < 0.05). Tiaoxue Yisui recipe could improve the quality of the patient's life. The therapeutical mechanism of the Tiaoxue Yisui recipe might promote the proliferation of hemopoietic stem cells and regulate the immune function.


Membranous nephropathy in Japan: analysis of the Japan Renal Biopsy Registry (J-RBR).
Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. The J-RBR/J-KDR registry developed by the Japanese Society of Nephrology provides nationwide cohort data for epidemiological studies of MN. MN was present in 36.8% of 1,203 primary nephrotic syndrome patients in Japan. In addition, 633 (77.9%) out of 813 MN patients were referred to as "idiopathic," whereas 22.1% were classified as "secondary" and involved conditions such as systemic lupus erythematosus, drug exposure, infections, cancer, and various collagen diseases. The mean age of the MN patients was 62.2 (2-88) years old, their mean eGFR was 76.7 (7.6-154.6) ml/min/1.73 m(2), and 63.3% had hypertension at the time of renal biopsy. On the basis of these findings, half of Japanese idiopathic MN patients have risk factors (age >60, male, or lower eGFR) for end-stage renal failure, and 10% belong to the high-risk group (daily proteinuria of over 8.0 g). Further studies with high-grade evidence should resolve the natural history and therapeutic problems of idiopathic MN in elderly Japanese.


Formulation and mechanical properties of emulsion-based model polymer foams.
We produce cellular material based on the formulation of model emulsions whose drop size and composition may be continuously tuned. The obtained solid foams are characterized by narrow cell and pore size distributions in direct relation with the emulsion structure. The mechanical properties are examined, by varying independently the cell size and the foam density, and compared to theoretical predictions. Surprisingly, at constant density, Young's modulus depends on the cell size. We believe that this observation results from the heterogeneous nature of the solid material constituting the cell walls and propose a mean-field approach that allows describing the experimental data. We discuss the possible origin of the heterogeneity and suggest that the presence of an excess of surfactant close to the interface results in a softer polymer layer near the surface and a harder layer in the bulk.


Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression.
The pathogenesis of hepatitis C virus (HCV)-associated liver injury involves many genes from multiple pathogenic pathways. cDNA array analysis, which examines the expression of many genes simultaneously, was used to achieve new insights into HCV liver injury. Membrane-based cDNA arrays of 874 genes compared HCV-associated cirrhosis with autoimmune hepatitis-associated cirrhosis as an inflammatory and cirrhotic control, and with nondiseased liver tissue. Array analysis identified many differentially expressed genes that are important in inflammation, fibrosis, proliferation, signaling, apoptosis, and oxidative stress. Genes up-regulated in HCV-associated cirrhosis were predominantly associated with a Th1 immune response, fibrosis, cellular proliferation, and apoptosis. Novel observations of differential gene expression included increased expression of secreted apoptosis-related protein 3, a Wnt pathway gene possibly involved in cellular apoptosis. EMMPRIN (CD147) and discoidin domain receptor 1 (CD167) were also shown to be increased and are likely to play a role in liver fibrosis. Real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of 15 genes. The comparison of HCV cirrhosis with autoimmune hepatitis cirrhosis showed a marked difference in the apoptosis-associated gene profile with HCV cirrhosis characterized by increased proapoptotic gene expression whereas autoimmune hepatitis was characterized by increased expression of both antiapoptotic and proapoptotic genes. Furthermore, expression of beta-catenin and the fibrosis-associated protein EMMPRIN were localized by immunohistochemistry to the plasma membranes of hepatocytes and biliary epithelium. In conclusion, HCV-associated cirrhosis was characterized by a proinflammatory, profibrotic, and proapoptotic gene expression profile.


Human Versus Machine: How Do We Know Who Is Winning? ROC Analysis for Comparing Human and Machine Performance under Varying Cost-Prevalence Assumptions.
Receiver operating characteristic (ROC) analysis is commonly used for comparing models and humans; however, the exact analytical techniques vary and some are flawed. The aim of the study is to identify common flaws in ROC analysis for human versus model performance, and address them. We review current use and identify common errors. We also review the ROC analysis literature for more appropriate techniques. We identify concerns in three techniques: (1) using mean human sensitivity and specificity; (2) assuming humans can be approximated by ROCs; and (3) matching sensitivity and specificity. We identify a technique from Provost et al using dominance tables and cost-prevalence gradients that can be adapted to address these concerns. Dominance tables and cost-prevalence gradients provide far greater detail when comparing performances of models and humans, and address common failings in other approaches. This should be the standard method for such analyses moving forward.


Assessment of Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios in patients with acromegaly.
Cardiovascular complications, including ventricular arrhythmias associated with abnormalities of ventricular repolarization, are the leading cause of morbidity and mortality in patients with acromegaly. Herein, we aimed to investigate ventricular repolarization using Tp-e interval, Tp-e interval/QT, and Tp-e interval/QTc ratios in acromegalic patients compared to healthy subjects. A total of 29 patients (aged 51.9 ± 11.2, 65.5% women) with acromegaly and 30 control subjects (aged 47.3 ± 14.4, 63.3% women) were enrolled in the study. Tp-e and QT interval, corrected QT (QTc), Tp-e/QT, and Tp-e/QTc ratios were calculated from the 12-lead electrocardiogram. Tp-e interval (89.28 ± 12.16 vs. 75.97 ± 9.92 ms; p < 0.001), Tp-e/QT ratio (0.237 ± 0.045 vs. 0.212 ± 0.029; p = 0.019), and Tp-e/ QTc ratio (0.218 ± 0.031 vs. 0.195 ± 0.026; p = 0.003) were significantly higher in patients with acromegaly compared to control group. A positive correlation was determined between left atrial volume index (LAVI) and Tp-e interval (r = 0.272, p = 0.039). The current study is the first to have shown significantly increased Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were increased in acromegalic patients. These results may be important for screening malignant arrhythmic events in acromegaly.


Corrigendum.
Pages H1237–H1250: Leone M, Magadum A, Engel FB. Cardiomyocyte proliferation in cardiac development and regeneration: a guide to methodologies and interpretations. Am J Physiol Heart Circ Physiol 309: H1237–H1250, 2015. First published September 4, 2015; doi:10.1152/ajpheart.00559.2015 (http://ajpheart.physiology.org/content/309/8/H1237.long).—Under Newborn mouse heart regeneration, the value for the increase in cell number upon Meis1 deletion is corrected as shown in boldface as follows: In fact, the cell number data indicate that Meis1 deletion induced the production of 0.2 million cardiomyocytes in less than 5 wk by an H3P as well as Aurora B fold increase of less than fourfold.


Demand for alcohol treatment by problem drinkers.
Problem drinkers applying for treatment at both outpatient and inpatient treatment programs were compared with problem drinkers identified in a general population survey. The characteristics in which these populations differ were interpreted as factors contributing to the demand for treatment and, thus, indicative of the need for alcohol treatment. Older problem drinkers appear to apply for treatment more frequently, and the same is true for divorced and unemployed or disabled problem drinkers. More important, age, marital status, and employment status were found to contribute to the demand for alcohol treatment independent of alcohol consumption. It can be concluded from this study that the demand for alcohol treatment is not determined by alcohol consumption alone, suggesting that alcohol treatment should not only focus on alcohol consumption but also focus on problems related to marital and employment status in order to prevent future need for alcohol treatment.


Staged lesions through implanted deep brain stimulating electrodes: a new surgical procedure for treating tremor or dyskinesias.
Thalamotomy and pallidotomy have been shown to have some efficacy for treating some movement disorders such as disabling tremor or parkinsonian levodopa-induced dyskinesias (LID). Compared to continuous deep brain stimulation (DBS), this surgical procedure has the disadvantage of irreversibility and a lack of adaptability. Making a lesion involves a risk of inducing permanent side effects, especially if the lesion is large, or of observing a resurgence of the symptoms if the lesion is too small. We performed unilateral pallidotomy in one patient suffering from LID and unilateral thalamotomy in two patients suffering from tremor through the lead classically used for DBS. The technique of lead implantation was similar to that used for DBS treatment but, instead of connecting the lead to a pulse generator, it was left in place and used to make a radiofrequency lesion. This technique allowed the lesion to be kept as small as possible, thereby minimizing the risk of permanent side effects and made possible to extend the lesion if the symptoms reappeared. One lesioning session was enough to relieve tremor in the two patients treated by thalamotomy; three lesioning sessions over a 7-month period were required to relieve drug-induced dyskinesias in the patient treated by pallidotomy. In all 3 patients, disabling symptoms were still relieved without any permanent side effects 6 months after the last lesion was performed.


Comparison of patient perceived primary care quality in public clinics, public hospitals and private clinics in rural China.
In rural China, patients have free choice of health facilities for outpatient services. Comparison studies exploring the attributes of different health facilities can help identify optimal primary care service models. Using a representative sample of Chinese provinces, this study aimed to compare patients' rating of three primary care service models used by rural residents (public clinics, public hospitals and private clinics) on a range of health care attributes related to responsiveness. This was a secondary analysis using the household survey data from World Health Organization (WHO) Study on global AGEing and adult health (SAGE). Using a multistage cluster sampling strategy, eight provinces were selected and finally 3435 overall respondents reporting they had visited public clinics, public hospitals or private clinics during the last year, were included in our analysis. Five items were used to measure patient perceived quality in five domains including prompt attention, communication and autonomy, dignity and confidentiality. ANOVA and Turkey's post hoc tests were used to conduct comparative analysis of five domains. Separate multivariate linear regression models were estimated to examine the association of primary care service models with each domain after controlling for patient characteristics. The distribution of last health facilities visited was: 29.5% public clinics; 31.2% public hospitals and; 39.3% private clinics. Public clinics perform best in all five domains: prompt attention (4.15), dignity (4.17), communication (4.07), autonomy (4.05) and confidentiality (4.02). Public hospitals perform better than private clinics in dignity (4.03 vs 3.94), communication (3.97 vs 3.82), autonomy (3.92 vs 3.74) and confidentiality (3.94 vs 3.73), but equivalently in prompt attention (3.92 vs 3.93). Rural residents who are older, wealthier, and with higher self-rated health status have significantly higher patient perceived quality of care in all domains. Rural public clinics, which share many characteristics with the optimal primary care delivery model, should be strongly strengthened to respond to patients' needs. Better doctor-patient interaction training would improve respect, confidentiality, autonomy and, most importantly, health care quality for rural patients.


Numbers around Descartes: A preregistered study on the three-dimensional SNARC effect.
The Spatial-Numerical Association of Response Codes (SNARC) effect suggests that numbers are represented along a horizontal left-to-right oriented, mental number line, with small numbers on the left and large numbers on the right. Much less evidence exists for vertical (down-to-up) and sagittal (near-to-far) SNARC effects. This might be due to the employment of different experimental paradigms among studies and to the, sometimes, inexact definition of the vertical and sagittal axes. We investigated for the first time the SNARC effect along the horizontal, vertical, and sagittal axes, by means of a classic SNARC task. Our results suggest the presence of three equally-strong SNARC effects. Our findings can be considered as evidence in favor of a three-dimensional, mental representation of numbers, in the form of a mental number space, defined by Cartesian coordinates.


Child survival in relation to mother's HIV infection and survival: evidence from a Ugandan cohort study.
To analyse the contribution of maternal survival and HIV status to child (under-5 years) mortality in a rural population cohort in South-west Uganda. Approximately 10 000 people residing in 15 neighbouring villages were followed between 1989 and 2000 using annual censuses and serological surveys to collect data on births, deaths, and adult HIV serostatus. Mother-child records were linked, child mortality risks (per 1000 births) and hazard ratios (HRs) for child mortality according to maternal HIV serostatus were computed, allowing for time-varying covariates. A total of 3727 children were born, of whom 415 died during 14 110 child years of follow-up. Mother's HIV status at birth was ascertained unambiguously for 3004 children, of whom 218 were born to HIV-positive mothers. Infant mortality risk was higher for HIV seropositive than seronegative mothers (225 versus 53) as was child mortality risk (313 versus 114). Child mortality risk was also higher for mothers who died (571) than for surviving mothers (128). After controlling for child's age and sex, independent predictors of mortality in children were: mother's terminal illness or death (HR = 3.8); mother being HIV positive (HR = 3.2); child being a twin (HR = 2.0); teenage motherhood (HR = 1.7) and maternal absence (HR = 1.7). Maternal survival and HIV status are strong predictors of child survival. The higher mortality in HIV-infected women compounds mortality risks for their children, regardless of children's HIV status. Programmes aimed at the welfare of children should take into account the independent effect of mothers' HIV and vital status.


Comprehensive analysis between volatile organic compound (VOC) exposure and female sex hormones: a cross-sectional study from NHANES 2013-2016.
There is growing evidence suggesting that exposure to volatile organic compounds (VOCs) can pose significant health risks, including interference with the function of the reproductive system. However, there has been a lack of research focused on the impact of common environmental VOCs on the levels of sex hormones in the general female population. In this study, we conducted a cross-sectional analysis utilizing the database of the National Health and Nutrition Examination Survey (NHANES, 2013-2016). A total of 2633 participants were included in this study. The Pearson correlation model revealed the potential of co-exposure or co-toxicity between benzene and 2,5-dimethylfuran. According to GLM models, we discovered a significant positive association between blood levels of 2,5-dimethylfuran and benzene with testosterone levels in women. Subgroup analysis further identified that the women with underweight and healthy weight might be the high-risk subgroup. Bayesian kernel machine regression (BKMR) was applied to further assess the univariate and bivariate exposure-response relationships between multiple VOCs. Our research systemically formulated the possible relationship between exposure to VOCs and female sex hormones, indicating the role of VOCs as a risk factor for endocrine disruption, especially benzene and 2,5-dimethylfuran. These findings have important implications for public health and call for further investigation.


[Transvaginal ultrasound assessment of physiological changes of Chinese women's cervix].
To observe Chinese women's cervical physiological changes by transvaginal ultrasound. 637 normal female volunteers were studied. Cervical length, width and canal width were measured by transvaginal ultrasound. Cervical length multiplied by width was the biggest vertical section area of cervix(cervical area). The cervical length, width, area and canal width in the menopausal women were significant smaller than that in the un-menopausal women (P < 0.0001). Multinomial logistic regression showed that cervical changes were mainly affected by menopause year, gestation and para. The cervical length, width, area and canal width were negative correlated with menopause year significantly. The cervical and canal width were positive correlated with gestation. The regressive equation was Cervical area (cm2) = 3.69 + 0.23 Gastation -0.16 Menopause year. Cervical physiological changes are mainly affected by the menopause year, gestation and para. The menopause year is the most important factor in the cervical physiological changes.


Systematic Review of Contemporary Theories Used for Co-creation, Co-design and Co-production in Public Health.
There is a need to systematically identify and summarize the contemporary theories and theoretical frameworks used for co-creation, co-design and co-production in public health research. The reporting of this systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Given substantial interest in and application of co-creation, co-design and co-production, we searched PubMed, CINAHL, Scopus and APA PsycINFO from 2012 to March-April 2022. A quality assessment and data extraction for theory content was performed. Of the 3763 unique references identified through the comprehensive search strategy, 10 articles were included in the review: four articles named co-creation, two articles named co-creation and co-design, two articles named co-production and co-design, and two articles named co-design. Empowerment Theory was employed by two articles, whereas other theories (n = 5) or frameworks (n = 3) were employed by one article each. For the quality assessment, eight articles received a strong rating and two articles received a moderate rating. There is little indication of theory applications for the approaches of co-creation, co-design and co-production in public health since 2012, given 10 articles were included in this review. Yet, the theories described in these 10 articles can be useful for developing such co-approaches in future public health research.


Candidate genes involved in the susceptibility of primary open angle glaucoma.
Glaucoma is a common disease often identified by high intraocular pressure, characteristic optic neuropathy and vision loss. It is currently a leading cause of blindness worldwide with no known cure. Primary open angle glaucoma (POAG) is the most common type of glaucoma worldwide. It is a multifactorial disease where both genetic as well as environmental factors are involved in the pathogenesis. Till date, at least 29 genetic loci have been found to be linked to POAG. However, the role of only three underlying genes Myocilin (MYOC), Optineurin (OPTN) and WD repeat Domain 36, (WDR36) is well established. Also, the role of Cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), Glutathione S-transferase mu 1 (GSTM1) and Neurotrophin (NTF4) has been fairly identified. Association studies have found that 66 loci with 76 genes associated to POAG till date, but even more studies are required to confirm their role in the disease pathology. Gene mutations in various populations have been identified by genetic studies to establish that about 5% of POAG is currently attributed to single-gene or Mendelian forms of glaucoma and others caused by the combined effects of many genetic and environmental risk factors, each of which do not act alone to cause glaucoma. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are poorly understood and thus the etiology of POAG remains a mystery. Despite strong genetic influence in POAG pathogenesis, only a small part of the disease can be explained in terms of genetic aberration. This review is an overview and update on the latest research and progress of genetic studies associated with POAG.


An organic light-emitting diode display for use in neuroendoscopic surgery in the ventricle.
The organic light-emitting diode (OLED) display delivers a bright and high-contrast image compared to the liquid crystal display. The first experience of neuroendoscopic surgery using an OLED display was reported and its stereoscopic effect emphasized.


Reflections on tuberculosis diagnosis and treatment outcomes in Ghana.
Available evidence in Ghana shows the implementation of tuberculosis (TB) control activities efforts since the beginning of the 1900s. In spite of that, TB continues to be one of the common diseases in the country. In 1994, local and international policy windows opened for renewed strategies for the control of TB. This paper explores some of the approaches which have been in place since 1994 and their implications for treatment outcomes. The study combines quantitative and qualitative data. The quantitative data consist of treatment outcome from 1997-2010 and the qualitative data are derived from in-depth interviews with some staff of the TB control programme. Poisson regression and inductive coding were applied to the quantitative and qualitative data respectively. Reported cure rates increased from 43.6% to 87.7% between 1997 and 2010. The data from the in-depth interviews (IDIs) suggested that improvements in diagnosis, community TB care, stigma reduction among community and health workers towards TB patients, the public-private partnership, and the enablers' package contributed to the improved better treatment outcomes, particularly from 2008. Lessons learnt include the achievement of objectives with varying strategies and stakeholder interventions. Further studies would be needed to quantify the contributions of the various interventions to help determine those that are cost effective as well as efficient and effective for TB control.


Curacin D, an antimitotic agent from the marine cyanobacterium Lyngbya majuscula.
Curacin D is a novel brine shrimp toxic metabolite isolated from a Virgin Islands collection of the marine cyanobacterium Lyngbya majuscula. Structure elucidation of curacin D was accomplished through multidimensional NMR, GC/MS, and comparisons with curacin A. Curacin D provides new insights into structure-activity relationships in this natural product class as well as some aspects of the likely biosynthetic pathway of the curacins.


[Bronchoplasty and pulmonary arterioplasty for treatment of lung cancer].
We evaluated the outcomes of bronchoplasty (BP) and pulmonary arterioplasty (PAP) for treatment of patients with lung cancer. We studied 33 patients who underwent BP and/or PAP over the previous 7 years at our institution. A telescope procedure was utilized for anastomosis of a tubular excision performed in the bronchus. One patient received induction chemoradiotherapy, in whom the anastomosis section was covered with an intercostal muscle flap to assure anastomosis completion, then PAP was performed under heparinization. BP including a sleeve resection was performed in 15 patients, while that with a wedge resection and partial side wall resection was performed in 7 and 1 patient, respectively. PAP was performed in 18 patients, and a combination of BP and PAP was used in 8. The seam was incomplete in 2 patients and stenosis was recognized in the anastomosis section in 1. No local recurrence at the anastomosis site was seen in any of the 33 cases. The survival rate for patients who underwent BP was similar to that of those who underwent a standard resection for primary lung cancer. Our results indicate that BP and PAP are safe and useful surgical procedures for patients with lung cancer.


Rational fabrication of cadmium-sulfide/graphitic-carbon-nitride/hematite photocatalyst with type II and Z-scheme tandem heterojunctions to promote photocatalytic carbon dioxide reduction.
Artificial photosynthesis has become one of the most attractive strategies for lowering atmospheric carbon dioxide (CO2) level and achieving the carbon balance; whereas, the fast electron-hole recombination and sluggish charge transfer in photocatalysts are themain stumbling blocks to the applications. Constructing semiconductor nano-heterostructures provides a promising strategy to accelerate the separation and transfer of photoinduced charge carriers for promoting the multielectron CO2 reduction reaction. Herein, a CdS/g-C3N4/α-Fe2O3 three-component photocatalyst consisting of type II and Z-scheme tandem heterojunctions is skillfully fabricated via the solvothermal synthesis followed with photoinduced deposition. The CdS/g-C3N4/α-Fe2O3 tandem-heterojunction photocatalyst exhibits superior performance toward the conversion of CO2 to fuels (CO and CH4), compared with the single- and binary-component systems, owing to the favorable energy-level alignment, accelerated charge separation, facilitated water dissociation and sufficient reactive-hydrogen provision. The total consumed electron number of CdS/g-C3N4/α-Fe2O3 catalyst for CO2 reduction is about 10.5 times that of pure g-C3N4. The photocatalytic mechanism is elucidated according to detailed characterizations and in-situ spectroscopy analyses. This work sheds light on the rational construction of heterojunction photocatalysts to promote the conversion of CO2 to solar fuels, without using any sacrifice reagent or noble-metal cocatalysts.


Bilateral asymmetry prediction.
This study predicts asymmetries in lateral organ cancer incidence from text mining of the Medline database. Lung, kidney, teste, and ovary cancers were examined. For each cancer, Medline case report articles focused solely on (1) cancer of the right organ and (2) cancer of the left organ were retrieved. The ratio of right organ to left organ articles was compared to actual patient incidence data obtained from the National Cancer Institute's (NCI) SEER database for the period 1979-1998. The agreement between the Medline record ratios and the NCI's patient incidence data ratios ranged from within 3% for lung cancer to within 1% for teste and ovary cancer. This is the first known study to generate cancer lateral incidence asymmetries from the Medline database. The technique should be applicable to other diseases and other types of system asymmetries.


Spontaneous honeybee behaviour is altered by persistent organic pollutants.
The effect of environmental pollutants on honeybee behaviour has focused mainly on currently used pesticides. However, honeybees are also exposed to persistent organic pollutants (POPs). The aim of this laboratory based study was to determine if exposure to sublethal field-relevant concentrations of POPs altered the spontaneous behaviour of foraging-age worker honeybees. Honeybees (Apis mellifera) were orally exposed to either a sublethal concentration of the polychlorinated biphenyl (PCB) mixture Aroclor 1254 (100 ng/ml), the organochlorine insecticide lindane (2.91 ng/ml) or vehicle (0.01% DMSO, 0.00015% ethanol in 1M sucrose) for 1-4 days. The frequency of single event behaviours and the time engaged in one of four behavioural states (walking, flying, upside down and stationary) were monitored for 15 min after 1, 2, 3 and 4 days exposure. Exposure to Aroclor 1254 but not lindane increased the frequency and time engaged in honeybee motor activity behaviours in comparison to vehicle. The Aroclor 1254-induced hyperactivity was evident after 1 day of exposure and persisted with repeated daily exposure. In contrast, 1 day of exposure to lindane elicited abdominal spasms and increased the frequency of grooming behaviours in comparison to vehicle exposure. After 4 days of exposure, abdominal spasms and increased grooming behaviours were also evident in honeybees exposed to Aroclor 1254. These data demonstrate that POPs can induce distinct behavioural patterns, indicating different toxicokinetic and toxicodynamic properties. The changes in spontaneous behaviour, particularly the PCB-induced chronic hyperactivity and the associated energy demands, may have implications for colony health.