Formal Hepatitis C Education Increases Willingness to Receive Therapy in an On-site Shelter-Based HCV Model of Care in Persons Experiencing Homelessness.
The objective of this study was to evaluate the effectiveness of formal hepatitis C virus (HCV) education on engagement in therapy in persons experiencing homelessness in an on-site shelter-based model of care. As policies to eliminate Medicaid access restrictions to HCV treatment are expanded, patient education is paramount to achieving HCV elimination targets in difficult-to-engage populations including persons experiencing homelessness. This prospective study was conducted at 4 shelters in San Francisco and Minneapolis from August 2018 to January 2021. Of the 162 HCV Ab-positive participants, 150 participated in a 30-minute HCV education session. Posteducation changes in knowledge, beliefs, barriers to care, and willingness to accept therapy scores were assessed. Following education, knowledge scores (mean change, 4.4 ± 4.4; P < .001) and willingness to accept therapy (70% to 86%; P = .0002) increased. Perceived barriers to HCV care decreased (mean change, -0.8 ± 5.2; P = .001). Higher baseline knowledge was associated with lesser gain in knowledge following education (coef., -0.7; P < .001). Posteducation knowledge (odds ratio, 1.2; P = .008) was associated with willingness to accept therapy. An HCV educational intervention successfully increased willingness to engage in HCV therapy in persons experiencing homelessness in an on-site shelter-based HCV model of care.


Impact of abutment material and dis-/re-connection on soft and hard tissue changes at implants with platform-switching.
To assess the impact of abutment material and dis-/re-connection on soft and hard tissue changes at implants with platform-switching. Titanium implants (n = 12), placed epicrestally in the upper jaws of three dogs, were connected with titanium (Ti) and zirconium dioxide (ZrO(2) ) abutments (horizontal mismatch of 0.4 mm) and randomly allocated in a split-mouth design either to repeated (2x) dis-/re-connection at 4 and 6 weeks (test), respectively, or left undisturbed (control). At 8 weeks, histomorphometrical measurements were made between the mucosal margin (PM), implant shoulder (IS) and the apical extension of the long junctional epithelium (aJE),-the most coronal level of bone in contact with the implant (CBI). Repeated abutment manipulation was associated with increased mean PM-aJE and IS-CBI values at both Ti (1.82 ± 0.37-1.99 ± 0.40 mm and 0.72 ± 0.18-1.12 ± 0.60 mm) and ZrO(2) (1.90 ± 0.28-2.67 ± 0.67 mm and 0.22 ± 0.10-2.15 ± 0.77 mm) abutments at 8 weeks. These vertical dimensions were comparable at both vestibular and oral aspects. Between group comparisons, however, failed to reveal a significant difference between test and control sites. Repeated manipulation may be associated with dimensional changes of peri-implant soft and hard tissues formed at both non-matching Ti and ZrO(2) abutments.


3D Hierarchical Pt-Nitrogen-Doped-Graphene-Carbonized Commercially Available Sponge as a Superior Electrocatalyst for Low-Temperature Fuel Cells.
Three-dimensional hierarchical nitrogen-doped graphene (3D-NG) frameworks were successfully fabricated through a feasible solution dip-coating method with commercially available sponges as the initial backbone. A spongy template can help hinder the graphene plates restacking in the period of the annealing process. The Pt/3D-NG catalyst was synthesized employing a polyol reduction process. The resultant Pt/3D-NG exhibits 2.3 times higher activity for methanol electro-oxidation along with the improvement in stability as compared with Pt/G owing to their favorable features including large specific surface area, high pore volume, high N doping level, and the homogeneous dispersion of Pt nanoparticles. Besides, Pt/3D-NG also presents high oxygen reduction reaction (ORR) performance in acid media when compared with Pt/3D-G and Pt/G. This work raises a valid solution for the fabrication of 3D functional freestanding graphene-based composites for a variety of applications in fuel cell catalysis, energy storage, and conversion.


Impulse Oscillometry and Spirometry Small-Airway Parameters in Mild to Moderate Bronchiectasis.
Both impulse oscillometry and spirometry can reflect small-airway disorders. The objective of this work was to investigate the diagnostic value of impulse oscillometry and spirometry small-airway parameters and their correlation with radiology, disease severity, and sputum bacteriology in mild to moderate bronchiectasis (bronchiectasis severity index <9) and to validate these findings in sensitivity analyses (mild bronchiectasis). We recruited 94 subjects with mild to moderate bronchiectasis and 26 healthy subjects. The diagnostic value of small-airway parameters was compared using the receiver operating characteristic curve. Chest high-resolution computed tomography (HRCT), impulse oscillometry measurement, spirometry, and sputum culture were performed. Correlation between small-airway parameters and clinical indices was determined, adjusting for age, sex, body mass index, and smoking history. Sensitivity analyses were repeated when excluding subjects with bronchiectasis severity index ≥9 or HRCT score ≥13. Impulse oscillometry and spirometry small-airway parameters could discriminate mild to moderate bronchiectasis from healthy subjects and correlated significantly with HRCT score and the number of bronchiectatic lobes and the bronchiectasis severity index (all P < .01). Small-airway parameters were more aberrant in subjects with dyshomogeneity and cystic bronchiectasis but were independent of Pseudomonas aeruginosa isolation or the location of predominant bronchiectatic lobes. Spirometry, but not impulse oscillometry, small-airway parameters differed statistically between subjects with isolated peripheral-airway bronchiectasis and those with peripheral plus central-airway bronchiectasis (all P < .01). Subgroup analyses yielded similar findings, except for the lack of correlation between small-airway parameters and clinical parameters in subjects with HRCT score ≤6. Impulse oscillometry and spirometry small-airway parameters have similar diagnostic value in reflecting peripheral-airway disorders and correlate with the HRCT scores, the bronchiectasis severity index, and the number of bronchiectatic lobes in mild to moderate bronchiectasis. Assessment of small-airway parameters should be incorporated in future lung function investigations in bronchiectasis.


Voltage-gated K+ currents in mouse articular chondrocytes regulate membrane potential.
Membrane currents and resting potential of isolated primary mouse articular chondrocytes maintained in monolayer cell culture for 1-9 days were recorded using patch clamp methods. Quantitative RT-PCR showed that the most abundantly expressed transcript of voltage-gated K(+) channels was for K(V)1.6, and immunological methods confirmed the expression of K(V)1.6 α-subunit proteins. These chondrocytes expressed a large time- and potential-dependent, Ca(2+)-independent 'delayed rectifier' K(+) current. Steady-state activation was well-fit by a Boltzmann function with a threshold near -50 mV, and a half-activation potential of -34.5 mV. The current was 50% blocked by 1.48 mM tetraethylammonium, 0.66 mM 4-aminopyridine and 20.6 nM α-dendrotoxin. The current inactivated very slowly at membrane potentials in the range of the resting potential of the chondrocytes. Resting membrane potential of the chondrocytes at room temperature (19-21°C) and in 5 mM external K(+) was -46.4 ± 1.3 mV (mean ± s.e.m; n = 23), near the 'foot' of the activation curve of this K(+) current. Resting potential was depolarized by an average of 4.2 ± 0.8 mV by 25 mM TEA, which blocked about 95% of the K(+) current. At a membrane potential of -50 mV, the apparent time constant of inactivation (tau(in)) was 37.9 s, and the 'steady-state' current level was 19% of that at a holding potential of -90 mV; at -40 mV, tau(in) was 20.3 s, and 'steady-state' current was 5% of that at -90 mV. These results demonstrate that in these primary cultured, mouse articular chondrocytes steady-state activation of a voltage-gated K(+) current contributes to resting membrane potential. However, this current is also likely to have a significant physiological role in repolarizing the chondrocyte following depolarizing stimuli that might occur in conditions of membrane stretch. For example, activation of TRP('transient receptor potential') non-specific cation channels in these cells during cyclic loading and unloading of the joint cartilage, or in response to hypertonic challenge is expected to result in depolarization and Ca(2+) entry. Potassium currents are required to maintain the resting membrane potential.


Transcatheter ablation of posteroseptal accessory pathways using a venous approach and radiofrequency energy.
The efficacy of transcatheter ablation of atrioventricular (AV) accessory pathways (APs) located in the posteroseptal region using a right atrial approach and radiofrequency energy was evaluated. Fifty consecutive patients with APs in the posteroseptal region underwent radiofrequency catheter ablation. Manifest preexcitation was present in 36 patients and a concealed AP in 14. In 18 patients (group 1), the ventriculoatrial (VA) interval during orthodromic tachycardia was prolonged by 21 +/- 7 milliseconds (range, 10 to 30 milliseconds) with functional left bundle-branch block. In 16 patients (group 2), functional left bundle-branch block caused no VA interval prolongation. The remaining 16 patients (group 3) had no inducible left bundle-branch block during orthodromic tachycardia. Functional right bundle-branch block was induced in 30 patients with no effect on the VA interval. In group 1, of 14 patients with manifest preexcitation during sinus rhythm, 10 patients had a positive delta wave in lead V1. Of 10 group 2 patients with manifest preexcitation, only 5 had a positive delta wave in lead V1. In group 3, of 12 patients with manifest preexcitation, 7 exhibited a positive delta wave in lead V1. All posteroseptal APs were successfully ablated, and this was achieved via a right atrial approach in 48 patients and left ventricular approach in only 2. Successful sites were at the posteroseptal region of the tricuspid annulus (30 patients), within the terminal 1 cm of the coronary sinus including its ostium (16 patients), and at the inferomedial aspect of the right atrium posterior to the coronary sinus ostium (2 patients). The posteroseptal region of the left ventricle was the site of successful ablation in 2 patients. Six patients with a recurrence of AP conduction required a repeat ablation, with successful results in 5. Thirty-five patients had a complete electrophysiological evaluation 2 to 3 months after their successful ablation and were found to have no functioning AP. In 49 patients with a final successful ablation, no recurrence of symptoms was noted during a mean follow-up period of 12 +/- 9 months. Complications occurring in 3 patients were cardiac tamponade requiring surgical drainage and repair of a right ventricular tear, pericardial effusion with no hemodynamic consequence that spontaneously resolved, and a transient 2:1 atrioventricular block. These data suggest that posteroseptal APs are amenable to successful ablation using a right atrial approach. Success was achieved in 47 cases (94%) in this series even though the ECG and/or electrophysiological characteristics of the posteroseptal APs of some patients were suggestive of "left-sided" pathways.


DNA hybridization techniques and their application to the diagnosis of infectious diseases.
Several commercial DNA probe assays are widely used in clinical microbiology laboratories. These include culture-confirmation assays for Mycobacterium species, which are recommended by CDC because they are both rapid and accurate, and culture-confirmation assays for N. gonorrhoeae. Probe assays for direct detection of N. gonorrhoeae and C. trachomatis are also widely used in public health and large reference laboratories. In many cases, the probe assays have decreased the time to identification of positive cultures and improved detection of these pathogens because they do not depend on the presence of viable organisms to achieve a positive result. Nucleic acid amplification assays hold promise for the rapid detection and identification of many infectious agents. PCR using universal primers enables researchers to identify new agents of disease that cannot be cultured in vitro; more importantly, PCR provides a method for detecting the presence of any bacterial species, including common organisms, in normally sterile body fluids, such as blood and cerebrospinal fluids. The use of such primers may well give PCR the broad-based approach needed to identify organisms in the clinical microbiology laboratory of the future.


Is the prevalence of anemia in children living at high altitudes real? An observational study in Peru.
Anemia diagnosis in populations residing at high altitude (HA) involves an adjustment of hemoglobin (Hb) values owing to the increase in its concentration with altitude. The suitability of the adjustment has been questioned since Hb concentrations depend on how adapted a population is to HA. In Peru, anemia in preschool children (PSC) is a matter of severe public concern for its high rates; in the city of Puno (∼3800 MASL), for example, 67.7% of children under 3 years are diagnosed with anemia. Here, we conducted an observational study in PSC living at different altitudes in Puno to assess Hb, iron status, and the suitability of altitude-adjusted Hb values in defining iron deficiency anemia. After adjusting Hb, 65.66% of the population had anemia, while only 4.8% of PSC had anemia when using unadjusted Hb. Receiver-operating characteristic curves using total body iron (TBI) as a marker of iron status are presented. In the 36- to 59-month age group, unadjusted Hb performed better than altitude-adjusted Hb. In the 6- to 35-month age group, anemia (adjusted or unadjusted) was not associated with TBI. We conclude that Hb adjustment by altitude is not appropriate. Anemia at an early age is not entirely attributable to iron deficiency.


Normal oral, rectal, tympanic and axillary body temperature in adult men and women: a systematic literature review.
Normal oral, rectal, tympanic and axillary body temperature in adult men and women: a systematic literature review The purpose of this study was to investigate normal body temperature in adult men and women. A systematic review of data was performed. Searches were carried out in MEDLINE, CINAHL, and manually from identified articles reference lists. Studies from 1935 to 1999 were included. Articles were classified as (1) strong, (2) fairly strong and (3) weak evidence. When summarizing studies with strong or fairly strong evidence the range for oral temperature was 33.2-38.2 degrees C, rectal: 34.4-37.8 degrees C, tympanic: 35.4- 37.8 degrees C and axillary: 35.5-37.0 degrees C. The range in oral temperature for men and women, respectively, was 35.7-37.7 and 33.2-38.1 degrees C, in rectal 36.7-37.5 and 36.8-37.1 degrees C, and in tympanic 35.5-37.5 and 35.7-37.5 degrees C. The ranges of normal body temperature need to be adjusted, especially for the lower values. When assessing body temperature it is important to take place of measurement and gender into consideration. Studies with random samples are needed to confirm the range of normal body temperature with respect to gender and age.


Burden of anaemia in rural and urban jat women in haryana state, India.
A cross-sectional study was undertaken on 600 Jat women (rural=300, urban=300), aged 40 to 70 years from Haryana state in North India. The aim of the study was to determine the prevalence of anaemia and the dietary intake of rural and urban middle-aged (40-59 years) and older (60 and above) Jat women. The findings indicated that all the subjects exhibited a decline in the mean values of haemoglobin (Hb) concentration with advancement in age. The mean blood Hb concentration of urban middle-aged and older women was 10.1±1.3g/dl and 9.91.4g/dl respectively, which was higher than their rural counterparts at all age groups, although the differences were statistically non-significant (p>0.05). The overall prevalence of anaemia reached 88.7% (rural women= 91.3%, urban women =86%). Daily dietary intake of rural and urban subjects was below the recommended dietary allowances. Physical performance of both groups of the women showed a decline with a decrease in Hb concentration. A significant and positive correlation of Hb status was observed with grip strength and vital capacity while a negative association was witnessed with blood pressure and pulse rate in both the rural and urban women. Anaemia among these women may be attributed to inadequate dietary intake, illiteracy, and poor access to health services.


[The effects of angiotensin II on gene expression of hepatic stellate cells].
Our previous investigation demonstrated that angiotensin II could induce proliferation and differentiation of hepatic stellate cells, and also could up-regulate its extracellular matrix synthesis. The objective of this study was to determine the effects of 10(-5) mol/L angiotensin II on gene expression of hepatic stellate cells. After incubation with 10(-5) mol/L angiotensin II for 48 hours, the cultured hepatic stellate cells were collected. The mRNA and total protein were obtained from cell lysate and then suppression subtractive hybridization (SSH), 2D-gel electrophoresis and MALDI-TOF mass spectrometry were used to identify these cDNAs and proteins. A total of 36 clones from the subtracted cDNA library were sequenced and compared to sequences in the GenBank using BLAST. Of the 36 differentially expressed gene fragments from the subtracted library, 13 differentially expressed gene fragments showed significant homology to other known proteins, such as ribosomal protein, beta-actin FE-3, leucyl-tRNA synthetase, CD147, pyruvate kinase, peroxiredoxin 1, and BAT3, while 2 other gene fragments encoding protein BC097361 and BC057380 and their functions were not disclosed. About 1110 and 1008 protein spots were detected by employing the ImageMaster 2D Platinum 4.9 proteome image analysis system in angiotensin-treated hepatic stellate cells and control cells separately. Among these spots 108 proteins were up-regulated while the other 153 proteins were down-regulated. Several up-regulated proteins were chosen to be excised and in-gel digest MALDI-TOF-MS and Database analysis showed that among the high expression proteins, there were prohibitin, RBL-NDP kinase 1.8x10(4) subunit, electron transfer flavoprotein alpha-subunit, guanine nucleotide binding protein, alpha 15, and heat shock 7.0x10(4) protein 5. Our results suggest that the up-regulation of hepatic stellate cell mRNA influences proliferation, differentiation and apoptosis of those cells. The proteins of signal transduction, metabolizing regulation, apoptosis suppression, and fibrogenesis regulation of hepatic stellate cells were up-regulated.


Living with hereditary haemorrhagic telangiectasia: coping and psychological distress - a cross-sectional study.
The purpose of this study was to examine the relationship between coping strategies measured by Coping Orientation to Problems Experienced Scale (COPE) and psychological distress measured by Hospital Anxiety and Depression Scale (HADS) and Becks Hopelessness Scale (BHS) in individuals living with Hereditary hemorrhagic telangiectasia (HHT) and to examine if coping strategies might have a mediating role between experienced illness and psychological distress. HHT is mainly caused by mutations in the ENG- or ALK1-genes and associated with a shorter life span. 90% of patients have recurrent nosebleeds. 66 individuals affected of HHT participated in this cross-sectional study, completing questions due to demographic variables, Experience of illness, COPE, BHS and HADS. X(2) test, bivariate correlations with Pearson r and hierarchical multiple regression were used using PASW 18. Experience of illness made the highest variance in anxiety, depression and hopelessness and the coping strategy "behavioral disengagement" seems to have a mediating role between nose bleedings, being afraid of complications, satisfied with life and psychological distress. Experience of illness is of big importance in psychological distress in individuals affected of HHT, and behavioral disengagement explained the actual relationship between experience of illness and psychological distress.


Biased interpretation and memory in children with varying levels of spider fear.
This study investigated multiple cognitive biases in children simultaneously, to investigate whether spider-fearful children display an interpretation bias, a recall bias, and source monitoring errors, and whether these biases are specific for spider-related materials. Furthermore, the independent ability of these biases to predict spider fear was investigated. A total of 121 children filled out the Spider Anxiety and Disgust Screening for Children (SADS-C), and they performed an interpretation task, a memory task, and a Behavioural Assessment Test (BAT). As expected, a specific interpretation bias was found: Spider-fearful children showed more negative interpretations of ambiguous spider-related scenarios, but not of other scenarios. We also found specific source monitoring errors: Spider-fearful children made more fear-related source monitoring errors for the spider-related scenarios, but not for the other scenarios. Only limited support was found for a recall bias. Finally, interpretation bias, recall bias, and source monitoring errors predicted unique variance components of spider fear.


Hepatic Macrophages in Liver Injury.
Ample evidence suggests that hepatic macrophages play key roles in the injury and repair mechanisms during liver disease progression. There are two major populations of hepatic macrophages: the liver resident Kupffer cells and the monocyte-derived macrophages, which rapidly infiltrate the liver during injury. Under different disease conditions, the tissue microenvironmental cues of the liver critically influence the phenotypes and functions of hepatic macrophages. Furthermore, hepatic macrophages interact with multiple cells types in the liver, such as hepatocytes, neutrophils, endothelial cells, and platelets. These crosstalk interactions are of paramount importance in regulating the extents of liver injury, repair, and ultimately liver disease progression. In this review, we summarize the novel findings highlighting the impact of injury-induced microenvironmental signals that determine the phenotype and function of hepatic macrophages. Moreover, we discuss the role of hepatic macrophages in homeostasis and pathological conditions through crosstalk interactions with other cells of the liver.


DG-GAN: A High Quality Defect Image Generation Method for Defect Detection.
The surface defect detection of industrial products has become a crucial link in industrial manufacturing. It has a series of chain effects on the control of product quality, the safety of the subsequent use of products, the reputation of products, and production efficiency. However, in actual production, it is often difficult to collect defect image samples. Without a sufficient number of defect image samples, training defect detection models is difficult to achieve. In this paper, a defect image generation method DG-GAN is proposed for defect detection. Based on the idea of the progressive generative adversarial, D2 adversarial loss function, cyclic consistency loss function, a data augmentation module, and a self-attention mechanism are introduced to improve the training stability and generative ability of the network. The DG-GAN method can generate high-quality and high-diversity surface defect images. The surface defect image generated by the model can be used to train the defect detection model and improve the convergence stability and detection accuracy of the defect detection model. Validation was performed on two data sets. Compared to the previous methods, the FID score of the generated defect images was significantly reduced (mean reductions of 16.17 and 20.06, respectively). The YOLOX detection accuracy was significantly improved with the increase in generated defect images (the highest increases were 6.1% and 20.4%, respectively). Experimental results showed that the DG-GAN model is effective in surface defect detection tasks.


Thermally tunable electric mie resonance of dielectric cut-wire type metamaterial.
In this manuscript, we present on a thermally tunable electric Mie resonance of dielectric cut-wire type metamaterial. Dielectric cut-wire exhibits Lorentz-type frequency dependent negative effective permittivity followed by zero value around its fundamental Mie resonance, resulting from dipole-oscillation of displacement currents. Furthermore, the operation frequency of electric resonance frequency can be varied by wire length and temperature variation. As environmental temperature changes by 40 °C, electric Mie resonance can be reversibly tuned by 1000 MHz, due to the thermal dependent permittivity character of ceramic.


Application of fluorescent nuclear track detectors for cellular dosimetry.
Ion beams radiotherapy with charged particles show greater relative biological effectiveness (RBE) compared to conventional photon therapy. This enhanced RBE is due to a localized energy deposition pattern, which is subject to large fluctuations on cellular scales. Fluorescent nuclear track detectors (FNTDs) based on Al2O3:C,Mg crystals coated with cells (Cell-Fit-HD) can provide information on individual cellular energy deposition. In this study we provide a theoretical framework to obtain the distribution of microscopic energy deposition and ionization density in cells exposed to ion beams and identifies contributions of five different sources of variations to the overall energy fluctuation at different depths of a biologically optimized spread-out Bragg peak. We show that fluctuation in the individual energy loss of the particles is the major source of variability while the fluctuation in particle hits plays a minor role. With the Cell-Fit-HD system the uncertainty arising from four of these sources, namely the nucleus area, the number of nuclear hits, the particle linear energy transfer and the chord length can be reduced and only energy loss straggling remains fundamentally unknown. The ability to quantify these factors results in a reduction of the uncertainty in cellular energy deposition from 24-55% down to only 7-12%. We have also shown current experimental results with FNTDs which show promising results, but need further improvements to reach the ideals predicted in this study.


On Physician-Industry Relationships and Unreasonable Standards of Proof for Harm: A Population-Level Bioethics Approach.
The primary claim of this paper is that a widely used argument against obstructing, curtailing, or eliminating deep physician-industry relationships is deficient. The typical argument critiqued requires that proof that physician-industry relationships cause harm flows from randomized controlled trials. Chief among the deficiencies in this claim is the fact that this specific demand for proof of harm essentially guts the precautionary principle. In so doing, the typical argument neuters the basic justification for public health action. In place of this fallacious move, the paper argues that proof of harm can be demonstrated via evidentiary standards widely accepted within the knowledge communities of public health scientists and epidemiologists. The paper concludes by noting that while there may be good reasons to oppose curtailment of deep physician-industry relationships, the typical argument described here is not among them.


Protection of piglets against atrophic rhinitis by vaccinating the sow with a vaccine against Pasteurella multocida and Bordetella bronchiseptica.
The efficacy of a new vaccine against atrophic rhinitis in pigs was tested in the Netherlands and Denmark. The vaccine contained protein dO (a truncated Pasteurella multocida toxin which is immunogenic and non-toxic), inactivated Bordetella bronchiseptica whole cells, and an adjuvant. The sows were either vaccinated intramuscularly with 2 ml of the vaccine at six to eight and two to four weeks before expected farrowing or left unvaccinated as controls. All the piglets were challenged intranasally with B bronchiseptica when three to seven days old and with P multocida three to four days later. Pigs born to the vaccinated sows performed significantly better than pigs born to the control sows when judged on growth, average daily weight gain and snout scores. The challenge organisms were reisolated more frequently from the control pigs than from the pigs in the vaccinated group. The vaccinated sows and their progeny developed high titres of antibodies against B bronchiseptica and P multocida toxin.


Instanton rate constant calculations using interpolated potential energy surfaces in nonredundant, rotationally and translationally invariant coordinates.
A trivial flaw in the utilization of artificial neural networks in interpolating chemical potential energy surfaces (PES) whose descriptors are Cartesian coordinates is their dependence on simple translations and rotations of the molecule under consideration. A different set of descriptors can be chosen to circumvent this problem, internuclear distances, inverse internuclear distances or z-matrix coordinates are three such descriptors. The objective is to use an interpolated PES in instanton rate constant calculations, hence information on the energy, gradient, and Hessian is required at coordinates in the vicinity of the tunneling path. Instanton theory relies on smoothly fitted Hessians, therefore we use energy, gradients, and Hessians in the training procedure. A major challenge is presented in the proper back-transformation of the output gradients and Hessians from internal coordinates to Cartesian coordinates. We perform comparisons between our method, a previous approach and on-the-fly rate constant calcuations on the hydrogen abstraction from methanol and on the hydrogen addition to isocyanic acid. © 2018Wiley Periodicals, Inc.


Hydrogen Bonds and n → π* Interactions in the Acetylation of Propranolol Catalyzed by Candida antarctica Lipase B: A QTAIM Study.
Enzyme-substrate interactions play a crucial role in enzymatic catalysis. Quantum theory of atoms in molecules (QTAIM) calculations are extremely useful in computational studies of these interactions because they provide very detailed information about the strengths and types of molecular interactions. QTAIM also provides information about the intramolecular changes that occur in the catalytic reaction. Here, we analyze the enzyme-substrate interactions and the topological properties of the electron density in the enantioselective step of the acylation of (R,S)-propranolol, an aminoalcohol with therapeutic applications, catalyzed by Candida antarctica lipase B. Eight reaction paths (four for each enantiomer) are investigated and the energies, atomic charges, hydrogen bonds, and n → π* interactions of propranolol, the catalytic triad (composed of D187, H224, and S105), and the oxyanion hole are analyzed. It is found that D187 acts as an electron density reservoir for H224, and H224 acts as an electron density reservoir for the active site of the protein. It releases electron density when the tetrahedral intermediate is formed from the Michaelis complex and receives it when the enzyme-product complex is formed. Hydrogen bonds can be grouped into noncovalent and covalent hydrogen bonds. The latter are stronger and more important for the reaction than the former. We also found weak n → π* interactions, which are characterized by QTAIM and the natural bond orbital (NBO) analysis.


Novel tests for evaluating two ROC curves under paired samples.
Disease prevention is important and can be accomplished by developing diagnostic tests. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) are used to assess the accuracy of diagnostic tests. The assessment for the superiority between evaluating two diagnostic tests is needed when comparing two diagnostic tests. Existing tests are constructed by comparing two AUCs under the paired samples. Nevertheless, it is problematic when two ROC curves are crossing. This article proposes a test that takes into account the possible correlation between pairs. Simulations are conducted to evaluate the feasibility of the test.


Diversity of Oligopeptide Transport in Yeast and Its Impact on Adaptation to Winemaking Conditions.
Nitrogen is an essential nutrient for yeasts and its relative abundance is an important modulator of fermentation kinetics. The main sources of nitrogen in food are ammonium and free amino acids, however, secondary sources such as oligopeptides are also important contributors to the nitrogen supply. In yeast, oligopeptide uptake is driven by different families of proton-coupled transporters whose specificity depends on peptide length. Proton-dependent Oligopeptide Transporters (POT) are specific to di- and tri-peptides, whereas the Oligopeptide Transport (OPT) family members import tetra- and pentapeptides. Recently, the novel family of Fungal Oligopeptide Transporters (FOT) has been identified in Saccharomyces cerevisiae wine strains as a result of a horizontal gene transfer from Torulaspora microellipsoides. In natural grape must fermentations with S. cerevisiae, Fots have a broader range of oligopeptide utilization in comparison with non-Fot strains, leading to higher biomass production and better fermentation efficiency. In this review we present the current knowledge on the diversity of oligopeptide transporters in yeast, also discussing how the consumption of oligopeptides provides an adaptive advantage to yeasts within the wine environment.


Pressure and stretch mechanosensitivity of peripheral nerve fibres following local inflammation of the nerve trunk.
Patients with non-specific limb pain often show signs of nerve mechanosensitivity, i.e. local tenderness over nerve trunks and pain in response to limb movements that cause nerve stretch. In such patients a nerve lesion is not apparent, and it has been suggested that local neural inflammation may be a key factor. The present study examines the extent to which nerve fibres in regions of local inflammation respond to small stretches, and whether functional changes occur throughout the primary afferent neurone. A local neuritis was induced in adult rats by wrapping oxidised cellulose saturated in complete Freund's adjuvant (CFA) around the peroneal or sciatic nerves. A small cut was made in the perineurium of some of the peroneal lesioned animals. A- and C-fibre recordings were made 2-10 days post-surgery from filaments dissected proximal to the lesion. Local mechanosensitivity was assessed using a glass probe and by small stretches. Responses to stretch and local pressure were recorded in 7% of C- and 8% of A-fibres from the peroneal nerve following CFA treatment with the sheath opened. A smaller proportion of stretch sensitive fibres were seen in sciatic and peroneal nerves after CFA treatment alone (2% of C- and 3% of A-fibres), but such fibres were not seen in control preparations. The most responsive fibres fired to 3% stretch, which is within the range of nerve stretch seen during normal limb movements. Less than 1% of stretch sensitive fibres had peripheral fields, indicating that most had probably degenerated distally.


[On the epidemic, prevention and treatment of Kala-Azar in northern Jiangsu in 1930s].
In the 1930s, the Kala-Azar spread rapidly and widely in 16 counties of northern Jiangsu, with infected victims amounted to 30,0000, yielding great damage to the society. The government of the Republic of China did strive for its prerention and treatment. Under whose guidance, there were Huaiyin Investigating Team for Kala-Azar and Prevention and Treatment Team of Huaiyin region for Kala-Azar with rather satisfactory results. However, the final outcome was poor because of bewilderment at epidemic way, deficiency of funds, underdeveloped economics and sanitation in the rural areas, the poor income of peasantry and faults in national preventing epidemic system, etc.


Advanced procedures for separation and analysis of low molecular weight inhibitor (NCXIF) of the cardiac sodium-calcium exchanger.
A low molecular weight inhibitor (NCX(IF)) of the cardiac Na/Ca exchanger, isolated from the calf ventricle tissue, is capable of regulating the muscle strip's contractility and relaxation without involving the beta-activation pathway. The structural analysis of NCX(IF) requires highly purified preparations that fulfill the demanding requirements for mass spectra and NMR analyses. No such preparation is yet available. To this end, new HPLC procedures were developed by a combination of the reverse phase, normal phase, and HILIC (hydrophilic liquid chromatography) techniques. The specific activity of NCX(IF) is 10(5) times higher in the purified preparations (as compared to the crude extract) showing a 2-5% yield of total inhibitory activity and 20-100 microg content of final material. The purification yield reveals that 1 kg ventricle muscle contains 0.1-0.2 mg NCX(IF), meaning that the tissue concentrations of NCX(IF) may reach 10(-7)-10(-6) M. The diode-array scanning of purified preparations of NCX(IF) shows a homogeneous 3D peak with a maximal absorption at 202 nm. These spectral properties may represent a five-membered ring (e.g., proline, histidine) and/or simple chemical groups (like amine, carbonyl, ester, etc.), but not an aromatic ring or complex conjugates (alkyne, alkene, aldehyde, etc.). NCX(IF) does not respond to phenol/sulfur reagent, suggesting that it lacks reducing (aldo) sugar. NCX(IF) shows a faint response to fluorescamine, meaning that it may contain an amino group (or its derivative). It is believed that a combination of presently developed procedures with LC/MS and LC/MS/MS may provide a useful tool for structural analysis of NCX(IF).


Primate encephalization and intelligence.
The amount of brain mass exceeding that related to an animal's total body mass is called encephalization. And quantifying encephalization has been argued to be directly related to an animal's level of intelligence. In this study, the legitimacy of the encephalization hypothesis was tested for encephalization slopes 0.28, 0.67, and 0.75 in Snell's equation of simple allometry by determining the intersexual encephalization similarity for humans and 18 other primate species and by comparing the encephalization quotients for humans and six other primate species against the learning ability evaluations for their intelligence. Results suggest that the most accurate means for quantifying the encephalization of humans and other adult primate species requires the use of Lapicque's universal exponent of 0.28 in Snell's equation of simple allometry. Since Lapicque's slope was derived from various vertebrate groups, this equation may potentially be universally applicable for determining relative adult vertebrate encephalization and intelligence.


Impact of Aspirin Eugenol Ester on Cyclooxygenase-1, Cyclooxygenase-2, C-Reactive Protein, Prothrombin and Arachidonate 5-Lipoxygenase in Healthy Rats.
Aspirin eugenol ester (AEE) is a promising drug candidate which is used for the treatment of inflammation, pain, fever, and the prevention of cardiovascular diseases. This study focuses on the effect of AEE on five proteins which are related to inflammation and thrombosis, including cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), C-reactive protein (CRP), prothrombin (FII) and arachidonate 5-lipoxygenase (ALOX5). Meanwhile, the study was administrated to compare the drug effect between AEE and its precursor from the view of chemical-protein interactions. Healthy rats were given AEE, aspirin, eugenol and integration of aspirin and eugenol. Carboxyl methyl cellulose sodium (CMC-Na) was used as control. After drugs were administered intragastrically for seven days, the blood samples were collected to measure the proteins concentration by enzyme linked immuno-sorbent assay (ELISA). The results showed that the concentrations of key endogenic bioactive enzymes were significantly reduced in AEE groups when compared with CMC-Na and aspirin groups (P < 0.01). Drug effects of AEE on five proteins were stronger than aspirin and eugenol. From the view of chemical-protein interactions, AEE had positive effects on anti-inflammation and anti-thrombosis and showed stronger effects than aspirin and eugenol.


Gemcitabine-Resistant Biomarkers in Bladder Cancer are Associated with Tumor-Immune Microenvironment.
To identify key biomarkers in gemcitabine (GEM)-resistant bladder cancer (BCa) and investigate their associations with tumor-infiltrating immune cells in a tumor immune microenvironment, we performed the present study on the basis of large-scale sequencing data. Expression profiles from the Gene Expression Omnibus GSE77883 dataset and The Cancer Genome Atlas BLCA dataset were analyzed. Both BCa development and GEM-resistance were identified to be immune-related through evaluating tumor-infiltrating immune cells. Eighty-two DEGs were obtained to be related to GEM-resistance. Functional enrichment analysis demonstrated they were related to regulation of immune cells proliferation. Protein-protein interaction network selected six key genes (CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4). Immunohistochemistry confirmed the down-regulation of the six key genes in BCa. Survival analyses revealed the six key genes were significantly associated with BCa overall survival. Correlation analyses revealed the six key genes had high infiltration of most immune cells. Gene set enrichment analysis further detected the key genes might regulate GEM-resistance through immune response and drug metabolism of cytochrome P450. Next, microRNA-gene regulatory network identified three key microRNAs (hsa-miR-124-3p, hsa-miR-26b-5p, and hsa-miR-192-5p) involved in GEM-resistant BCa. Connectivity Map analysis identified histone deacetylase inhibitors might circumvent GEM-resistance. In conclusion, CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4 were identified to be critical biomarkers through regulating the immune cell infiltration in an immune microenvironment of GEM-resistance and could act as promising treatment targets for GEM-resistant muscle-invasive BCa.


Alpha-melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury.
Mesenteric ischemia-reperfusion (I/R) injury to the intestine is a common and often devastating clinical occurrence for which there are few therapeutic options. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide released by the pituitary gland and immunocompetent cells that exerts anti-inflammatory actions and abrogates postischemic injury to the kidneys and brainstem of rodents. To test the hypothesis that alpha-MSH would afford similar protection in the postischemic small intestine, we analyzed the effects of this peptide on intestinal transit, histology, myeloperoxidase activity, and nuclear factor-kappaB (NF-kappaB) activation after 45 min of superior mesenteric artery occlusion and <or=6 h of reperfusion. Rats subjected to I/R exhibited markedly depressed intestinal transit, histological evidence of severe injury to the ileum, increased myeloperoxidase activity in ileal cytoplasmic extracts, and biphasic activation of NF-kappaB in ileal nuclear extracts. In contrast, rats treated with alpha-MSH before I/R exhibited intestinal transit and histological injury scores comparable to those of sham-operated controls. In addition, the alpha-MSH-treated rats demonstrated less I/R-induced activation of intestinal NF-kappaB and myeloperoxidase activity after prolonged (6 h) reperfusion. We conclude that alpha-MSH significantly limits postischemic injury to the rat small intestine.


Vascular manifestations of the thoracic outlet syndrome. A surgical urgency.
Although the vascular manifestations of the thoracic outlet syndrome are infrequent, their presence is an ominous portent for the affected limb. The cases of two recent patients indicate the importance of prompt recognition, urgent angiography, and definitive surgery. Regarding the surgical procedure, we used a two-incision approach-supraclavicular and intraclavicular-combining scalenotomy, resections of the cervical rib if present, the first thoracic rib, and the subclavian artery with retroclavicular interposition woven Dacron graft reconstruction. Preceding graft replacement, a Fogarty catheter thrombectomy of the distal brachial artery tree is done with completion arteriography to ensure freedom from retained distal thrombus. First rib resection is easily performed; subsequent vascular repair is also carried out, using this approach. We did not add sympathectomy to these cases, believing that early recognition and treatment will obviate its necessity. Follow-up has supported the efficacy of the treatment plan as presented.


Simultaneous determination of saponins and a flavonoid from aerial parts of Zygophyllum coccineum L.
Triterpenoid saponins are a class of glycosides with a wide range of bioactivities, which make them interesting research candidates. Zygophyllum coccineum is an Egyptian desert plant rich in triterpenoid saponins. Reviewing the relevant literature, no data concerning the HPLC or ultra-performance LC (UPLC) analysis of Zygophyllum content were found. This paper presents two methods, HPLC-UV and UPLC-UV-evaporative light scattering detector (ELSD)/MS, for the simultaneous determination of 10 compounds in the alcohol extract of Z. coccineum. The HPLC method uses a C18 column and water-acetonitrile (both containing 0.1% trifluoroacetic acid) gradient system. The separation was achieved within 32 min. The developed UPLC method simultaneously detects and quantifies the 10 compounds using an Acquity UPLC BEH Shield RP18 column and reagent alcohol-acetonitrile (80/20, v/v) and water (both containing 0.5% formic acid) gradient system within 14 min with UV, ELS, and MS detectors. The methods were used to analyze another species, Z. simplex, and results revealed a great variation between the secondary metabolite pattern of both species.


Deep brain electrophysiological recordings provide clues to the pathophysiology of Tourette syndrome.
Although ample evidence suggests that high-frequency deep brain stimulation (DBS) is an effective therapy in patients with Tourette syndrome (TS), its pathophysiology and the neurophysiological mechanisms underlying these benefits remain unclear. The DBS targets mainly used to date in TS are located within the basal ganglia-thalamo-cortical circuit compromised in this syndrome: the medial and ventral thalamic nuclei, which are way stations within the circuit, the globus pallidus and the nucleus accumbens. Neuronal activity can be electrophysiologically recorded from deep brain structures during DBS surgery (intraoperative microrecordings) or within few days after DBS electrode implantation (local field potentials, LFPs). Recordings from the thalamus in patients with TS showed that the power in low-frequency oscillations (2-15 Hz) was higher than power in high frequency oscillations (<45 Hz) and that activity in gamma band (25-45 Hz) increases when patients' clinical status improved. Effective thalamic DBS for tic reduction seems to increase high frequency band oscillations (25-45 Hz). The same oscillatory pattern persists after DBS for 1 year, therefore showing that in TS DBS does not induce persistent neuroplastic changes in the neural activity in the stimulated structures. Neurophysiological recordings from deep brain structures suggest that tics originate not from the cortex but from neuronal dysfunction in deep brain structures such as the thalamus and globus pallidus. In conclusion, DBS can induce its beneficial effects in TS by modulating specific neural rhythms in the cortico-basal ganglia thalamic network. DBS could reduce tics related increased low-frequency activity by shifting the basal ganglia-thalamic oscillation power to higher frequencies.


Herbivore-initiated interaction cascades and their modulation by productivity in an African savanna.
Despite conceptual recognition that indirect effects initiated by large herbivores are likely to have profound impacts on ecological community structure and function, the existing literature on indirect effects focuses largely on the role of predators. As a result, we know neither the frequency and extent of herbivore-initiated indirect effects nor the mechanisms that regulate their strength. We examined the effects of ungulates on taxa (plants, arthropods, and an insectivorous lizard) representing several trophic levels, using a series of large, long-term, ungulate-exclusion plots that span a landscape-scale productivity gradient in an African savanna. At each of six sites, lizards, trees, and the numerically dominant order of arthropods (Coleoptera) were more abundant in the absence of ungulates. The effect of ungulates on arthropods was mediated by herbaceous vegetation cover. The effect on lizards was simultaneously mediated by both tree density (lizard microhabitat) and arthropod abundance (lizard food). The magnitudes of the experimental effects on all response variables (trees, arthropods, and lizards) were negatively correlated with two distinct measures of primary productivity. These results demonstrate strong cascading effects of ungulates, both trophic and nontrophic, and support the hypothesis that productivity regulates the strength of these effects. Hence, the strongest indirect effects (and thus, the greatest risks to ecosystem integrity after large mammals are extirpated) are likely to occur in low-productivity habitats.


[Fiber-optic intubation with non-invasive ventilation with an endoscopic facial mask].
To assess the feasibility and safety of a new technique of fiberoptic bronchoscopy (FOB) tracheal intubation (TI) with noninvasive ventilation (NIV) via an endoscopic full facial mask with two openings, in case of acute respiratory failure (ARF) temporally improved by NIV, but requiring a mechanical ventilation. Clinical, prospective, open, noncomparative trial of feasibility with direct individual profit. Sixteen patients with ARF (age: 60 +/- 17 years, PaO2 = 59 +/- 16 mmHg, PaCO2 = 64 +/- 26 mmHg, PaO2/FIO2 = 142 +/- 70 before NIV) (m +/- SD), requiring TI. Including were: TI necessity (SpO2 < 90% or hypercapnic despite NIV, dependence of NIV, exhaustion, septic syndrome), clinical and SpO2 improvement with NIV. After i.v. injection of 5 mg midazolam and topical anesthesia (TA) of the nose, the endoscopic mask (modified Fibroxy, Péters) was applied to the face, fixed with elastic straps, then connected to the ventilatory support system with IPAP = 20 cmH2O, EPAP = 5 to 12 cmH2O, FIO2 = 1. A tube was slid on the FOB. As soon as SpO2[[[nbsp] 94%, the extremity of the FOB, was inserted through the lower opening of the mask, slid in the nostril, positioned in front of the glottis for AL, then pushed in the trachea authorizing AL and i.v. injection of 0.15 mg.kg-1 of etomidate (Ramsay[[[nbsp]3). The tube was then slid in the trachea, then, FOB was removed from trachea. The FOB intubation was easy at the patient's, without any failure or any complication. The procedure was 6.7 +/- 2 min. SpO2 significantly improved during TI, from 84 +/- 5% (FIO2 = 0.6 +/- 3) to 97 +/- 1 (FIO2 = 1 +/- 0), without decrease in oxygen saturation off 90%. Arterial pressure decreased only after the 5th min. The quantities of midazolam and of etomidate used were 4.6 +/- 2 mg and 12 +/- 4 mg. Three patients benefited from EPAP > 10 cmH2O. Fiberoptic tracheal intubation with NIV via an adapted endoscopic facial mask is a safe technique in patient with ARF temporally improved by NIV. This procedure requires TA and conscious sedation.


Symptomatology, evaluation and treatment of aquaductal stenosis.
Thirty-three surgical treated cases of aquaductal stenosis are presented. Beside the classical clinical representation of the disease, the symptomatology caused by anterior and posterior herniation of dilated third ventricle is discussed. The impotence in one male patient which is caused by anterior herniation was proved by means of NPT (Nocturnal Penile Tumescence) recording. In one patient bilateral partial deafness and Parinaud syndrome which was caused by posterior herniation was cured by third ventriculostomy. In the surgical treatment of aquaductal stenosis, the effectiveness of various surgical procedures are presented and the superiority of third ventriculostomy by microtechnique is emphasised.


Increased Calcium-Sensing Receptor Immunoreactivity in the Hippocampus of a Triple Transgenic Mouse Model of Alzheimer's Disease.
The Calcium-Sensing Receptor (CaSR) is a G-protein coupled, 7-transmembrane domain receptor ubiquitously expressed throughout the body, brain including. The role of CaSR in the CNS is not well understood; its expression is increasing during development, which has been implicated in memory formation and consolidation, and CaSR localization in nerve terminals has been related to synaptic plasticity and neurotransmission. There is an emerging evidence of CaSR involvement in neurodegenerative disorders and Alzheimer's disease (AD) in particular, where the over-production of β-amyloid peptides was reported to activate CaSR. In the present study, we performed CaSR immunohistochemical and densitometry analysis in the triple transgenic mouse model of AD (3xTg-AD). We found an increase in the expression of CaSR in hippocampal CA1 area and in dentate gyrus in the 3xTg-AD mice when compared to non-transgenic control animals. This increase was significant at 9 months of age and further increased at 12 and 18 months of age. This increase paralleled the accumulation of β-amyloid plaques with age. Increased expression of CaSR favors β-amyloidogenic pathway following direct interactions between β-amyloid and CaSR and hence may contribute to the pathological evolution of the AD. In the framework of this paradigm CaSR may represent a novel therapeutic target.


Extracapsular Lymph Node Involvement in Ovarian Carcinoma.
Ovarian cancer (OC) spread to retro-peritoneal lymph nodes is detected in about one out of two patients at primary diagnosis. Whether the histologic pattern of lymph node involvement i.e., intra-(ICG) or extracapsular (ECG) cancer growth may affect patients' prognosis remains unknown. The aim of the current study was to analyze the prevalence of ECG and ICG in lymph node positive ovarian cancer. We further investigated whether ECG may be related to patients' prognosis and whether biomarkers expressed in the primary tumor may predict the pattern of lymph node involvement. Lymph node samples stemming from 143 OC patients were examined for presence of ECG. Capsular extravasation was tested for statistical association with clinico-pathological variables. We further tested 27 biomarkers that had been determined in primary tumor tissue for their potential to predict ECG in metastatic lymph nodes. ECG was detected in 35 (24.5%) of 143 lymph node positive patients. High grade (p = 0.043), histologic subtype (p = 0.006) and high lymph node ratio (LNR) (p < 0.001) were positively correlated with presence of ECG. Both ECG (p = 0.024) and high LNR (p = 0.008) were predictive for shortened overall survival. A four-protein signature determined from the primary tumor tissue was associated with presence of concomitant extracapsular spread in lymph nodes of the respective patient. This work found extracapsular spread of lymph node metastasis to be a common feature of lymph node positive ovarian cancer. Since ECG was positively associated with grade, LNR and shortened overall survival, we hypothesize that the presence of ECG may be interpreted as an indicator of tumor aggressiveness.


Large scale cultivation of an anti-D (IgM) antibody producing human/mouse heterohybridoma.
A human/mouse heterohybridoma cell line secreting anti-Rh(D) antibody was established by the fusion of Epstein-Barr Virus (EBV) transformed human B lymphocytes and human/mouse heteromyelomas. During scaling-up the cell line was adapted to suspension culture, then medium composition was gradually altered into a more economical one. The adapted cell line has kept its multiplication and antibody secreting characteristics in the new medium. Parameters of large scale batch cultivation in bioreactors were optimized in working volume of 3.6 litre and production was carried out under these parameters in working volume of 24 litre. Optimized parameters were the follows: (i) the cell line is highly sensitive to dissolved oxygen (DO) level, its optimal DO is 10%; (ii) optimal inoculum cell count is 3 x 10(5) cell/ml; (iii) Marine-blade impeller was chosen for supporting the requested oxygen transfer. Using the optimized parameters HUMAN Co. Ltd. produces the Monoclonal Anti-D (IgM) reagent, which has been registered in 1995 in Hungary and now it is on the market.


Cytokine secretion and markers of inflammation in relation to acidosis among chronic hemodialysis patients.
Various cytokines are increased in hemodialysis (HD) patients, and are considered prognostic markers. Metabolic acidosis is common among chronic HD patients and is associated with survival. The relationship between acidosis and cytokines in HD patients has not been fully explored. The study aim was to measure pro- and anti-inflammatory cytokines in HD patients, with relation to bicarbonate levels. Forty-seven stable HD patients were included (male/female 28/19, mean age 70.4 ± 14.5 years). Blood tests were taken before a midweek dialysis session. Cytokine secretion from peripheral blood mononuclear cells was measured. Acidosis versus no acidosis (serum HCO3 – 21.5 ± 0.2 vs. 24.9 ± 0.3 mEq/l, p < 0.001) was associated with decreased secretion of the anti-inflammatory interleukin-10 (IL-10, 1.16 ± 0.11 vs. 1.71 ± 0.20 ng/ml, p = 0.023). Patients with acidosis had higher parathyroid hormone (PTH), calcium-phosphate product, protein intake and transferrin. Higher IL-10 was associated with increased IL-6 secretion, higher bicarbonate, younger age and lower PTH. In stable chronic HD patients, a possible direct relation exists between metabolic acidosis and IL-10.


The dynamic properties of mammalian skeletal muscle.
The dynamic characteristics of the rat gracilis anticus muscle at 17.5 degrees C have been determined by isotonic and isometric loading. For a fixed initial length these characteristics were represented either as a family of length-velocity phase trajectories at various isotonic afterloads or as a series of force-velocity curves at different lengths. An alternate method of viewing these data, the length-external load-velocity phase space, was also generated. When the muscle was allowed to shorten from different initial lengths, the velocity of shortening achieved at a given length was lower for longer initial lengths. The amount of departure was also dependent upon the isotonic load, the greater the load the greater the departure. The departures were not caused by changes in the elastic elements of the muscle or fatigue in the ordinary sense. When the behavior of the muscle was investigated at different frequencies of stimulation, the shortening velocity was a function of the number of stimulating pulses received by the muscle at a given frequency. The shortening velocity of the rat gracilis anticus muscle is, therefore, not only a function of load and length, but also of an additional variable related to the time elapsed from onset of stimulation.


Modeling stem cell nucleus mechanics using confocal microscopy.
Nuclear mechanics is emerging as a key component of stem cell function and differentiation. While changes in nuclear structure can be visually imaged with confocal microscopy, mechanical characterization of the nucleus and its sub-cellular components require specialized testing equipment. A computational model permitting cell-specific mechanical information directly from confocal and atomic force microscopy of cell nuclei would be of great value. Here, we developed a computational framework for generating finite element models of isolated cell nuclei from multiple confocal microscopy scans and simple atomic force microscopy (AFM) tests. Confocal imaging stacks of isolated mesenchymal stem cells were converted into finite element models and siRNA-mediated Lamin A/C depletion isolated chromatin and Lamin A/C structures. Using AFM-measured experimental stiffness values, a set of conversion factors were determined for both chromatin and Lamin A/C to map the voxel intensity of the original images to the element stiffness, allowing the prediction of nuclear stiffness in an additional set of other nuclei. The developed computational framework will identify the contribution of a multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on simple nuclear isolation protocols, confocal images and AFM tests.


In vivo selection of resistant E. coli after ingestion of milk with added drug residues.
Antimicrobial resistance represents a major global threat to modern medicine. In vitro studies have shown that very low concentrations of drugs, as frequently identified in the environment, and in foods and water for human and animal consumption, can select for resistant bacteria. However, limited information is currently available on the in vivo impact of ingested drug residues. The objective of our study was to evaluate the effect of feeding preweaned calves milk containing antimicrobial drug residues (below the minimum inhibitory concentration), similar to concentrations detected in milk commonly fed to dairy calves, on selection of resistant fecal E. coli in calves from birth to weaning. At birth, thirty calves were randomly assigned to a controlled feeding trial where: 15 calves were fed raw milk with no drug residues (NR), and 15 calves were fed raw milk with drug residues (DR) by adding ceftiofur, penicillin, ampicillin, and oxytetracycline at final concentrations in the milk of 0.1, 0.005, 0.01, and 0.3 µg/ml, respectively. Fecal samples were rectally collected from each calf once a week starting at birth prior to the first feeding in the trial (pre-treatment) until 6 weeks of age. A significantly greater proportion of E. coli resistant to ampicillin, cefoxitin, ceftiofur, streptomycin and tetracycline was observed in DR calves when compared to NR calves. Additionally, isolates from DR calves had a significant decrease in susceptibility to ceftriaxone and ceftiofur when compared to isolates from NR calves. A greater proportion of E. coli isolates from calves in the DR group were resistant to 3 or more antimicrobial drugs when compared to calves in the ND group. These findings highlight the role that low concentrations of antimicrobial drugs have on the evolution and selection of resistance to multiple antimicrobial drugs in vivo.


The drinking test: a current noninvasive technique to evaluate gastric accommodation and perception.
Impaired gastric accommodation has been proposed as an im- portant mechanism in the generation of functional dyspepsia. There is an interest in methods that allow recording and quantifica- tion of the gastric accommodation reflex. Drinking tests, with water or nutrients, have been developed as a noninvasive, inexpensive method to assess gastric perception and accommodation. These tests are easily performed, do not need any special equipment and are well tolerated by patients. Drink test results are reported as the maximum tolerated volume, individual and cumulative symptom scores. Patients with functional dyspepsia have showed lower max- imum tolerated volumes than healthy volunteers. In these patients the maximum tolerated volume reflects the severity of early satiety and predicts impaired gastric accommodation, but it remains un- clear what physiologic processes are assessed by the drinking tests. Results of drinking tests may be influenced by physiologic factors, thus these results do not guide therapy. Given these facts, drinking tests are best reserved for clinical research purposes evaluating functional dyspeptic patients or patients with gastroparesis.


HIV treatment and care services for adolescents: a situational analysis of 218 facilities in 23 sub-Saharan African countries.
In 2013, an estimated 2.1 million adolescents (age 10-19 years) were living with HIV globally. The extent to which health facilities provide appropriate treatment and care was unknown. To support understanding of service availability in 2014, Paediatric-Adolescent Treatment Africa (PATA), a non-governmental organisation (NGO) supporting a network of health facilities across sub-Saharan Africa, undertook a facility-level situational analysis of adolescent HIV treatment and care services in 23 countries. Two hundred and eighteen facilities, responsible for an estimated 80,072 HIV-infected adolescents in care, were surveyed. Sixty per cent of the sample were from PATA's network, with the remaining gathered via local NGO partners and snowball sampling. Data were analysed using descriptive statistics and coding to describe central tendencies and identify themes. Respondents represented three subregions: West and Central Africa (n = 59; 27%), East Africa (n = 77, 35%) and southern Africa (n = 82, 38%). Half (50%) of the facilities were in urban areas, 17% peri-urban and 33% rural settings. Insufficient data disaggregation and outcomes monitoring were critical issues. A quarter of facilities did not have a working definition of adolescence. Facilities reported non-adherence as their key challenge in adolescent service provision, but had insufficient protocols for determining and managing poor adherence and loss to follow-up. Adherence counselling focused on implications of non-adherence rather than its drivers. Facilities recommended peer support as an effective adherence and retention intervention, yet not all offered these services. Almost two-thirds reported attending to adolescents with adults and/or children, and half had no transitioning protocols. Of those with transitioning protocols, 21% moved pregnant adolescents into adult services earlier than their peers. There was limited sexual and reproductive health integration, with 63% of facilities offering these services within their HIV programmes and 46% catering to the special needs of HIV-infected pregnant adolescents. Results indicate that providers are challenged by adolescent adherence and reflect an insufficiently targeted approach for adolescents. Guidance on standard definitions for adherence, retention and counselling approaches is needed. Peer support may create an enabling environment and sensitize personnel. Service delivery gaps should be addressed, with standardized transition and quality counselling. Integrated, comprehensive sexual reproductive health services are needed, with support for pregnant adolescents.


How does the recurrence-related morphology characteristics of the Pcom aneurysms correlated with hemodynamics?
Posterior communicating artery (Pcom) aneurysm has unique morphological characteristics and a high recurrence risk after coil embolization. This study aimed to evaluate the relationship between the recurrence-related morphology characteristics and hemodynamics. A total of 20 patients with 22 Pcom aneurysms from 2019 to 2022 were retrospectively enrolled. The recurrence-related morphology parameters were measured. The hemodynamic parameters were simulated based on finite element analysis and computational fluid dynamics. The hemodynamic differences before and after treatment caused by different morphological features and the correlation between these parameters were analyzed. Significant greater postoperative inflow rate at the neck (Qinflow), relative Qinflow, inflow concentration index (ICI), and residual flow volume (RFV) were reported in the aneurysms with wide neck (>4 mm). Significant greater postoperative RFV were reported in the aneurysms with large size (>7 mm). Significant greater postoperative Qinflow, relative Qinflow, and ICI were reported in the aneurysms located on the larteral side of the curve. The bending angle of the internal carotid artery at the initiation of Pcom (αICA@PCOM) and neck diameter had moderate positive correlations with Qinflow, relative Qinflow, ICI, and RFV. The morphological factors, including aneurysm size, neck diameter, and αICA@PCOM, are correlated with the recurrence-inducing hemodynamic characteristics even after fully packing. This provides a theoretical basis for evaluating the risk of aneurysm recurrence and a reference for selecting a surgical plan.


Syntheses, structures, magnetism, and optical properties of lutetium-based interlanthanide selenides.
Ln3LuSe6 (Ln = La, Ce), beta-LnLuSe3 (Ln = Pr, Nd), and LnxLu4-xSe6 (Ln = Sm, Gd; x = 1.82, 1.87) have been synthesized using a Sb2Se3 flux at 1000 degrees C. Ln3LuSe6 (Ln = La, Ce) adopts the U3ScS6-type three-dimensional structure, which is constructed from two-dimensional 2(infinity)[Ln3Se6](3-) slabs with the gaps between these slabs being filled by octahedrally coordinated Lu(3+) ions. The series of beta-LnLuSe3 (Ln = Pr, Nd) are isotypic with UFeS3. Their structures include layers formed from LuSe6 octahedra that are separated by eight-coordinate Ln(3+) (Ln = Pr, Nd) ions in bicapped trigonal prismatic environments. Sm1.82Lu2.18Se6 and Gd1.87Lu2.13Se6 crystallize in the disordered F-Ln2S3 type structure with the eight-coordinate bicapped trigonal prismatic Ln(1) ions residing in the one-dimensional channels formed by three different double chains via edge- and corner-sharing. These double chains are constructed from Ln(2)Se7 monocapped trigonal prisms, Ln(3)Se6 octahedra, and Ln(4)S6 octahedra, respectively. The magnetic susceptibilities of beta-PrLuSe3 and beta-NdLuSe3 follow the Curie-Weiss law. Sm1.82Lu2.18Se6 shows van Vleck paramagnetism. Magnetic susceptibility measurements show that Gd1.87Lu2.13Se6 undergoes an antiferromagnetic transition around 4 K. Ce3LuSe6 exhibits soft ferromagnetism below 5 K. The optical band gaps for La3LuSe6, Ce3LuSe6, beta-PrLuSe3, beta-NdLuSe3, Sm1.82Lu2.18Se6, and Gd1.87Lu2.13Se6 are 1.26, 1.10, 1.56, 1.61, 1.51, and 1.56 eV, respectively.


Influence of pregnancy on dipeptidyl peptidase IV activity (CD 26 leukocyte differentiation antigen) of circulating lymphocytes.
Dipeptidyl peptidase IV (CD 26 leukocyte differentiation antigen) is an enzymic surface marker of a human T lymphocyte subpopulation which has been shown to be associated with their capacity to produce large amounts of interleukin 2 and proliferate strongly in response to mitogenic stimulation. The peptidase activity on the surface of purified human peripheral mononuclear cells was determined spectrophotometrically with the substrate glycyl-L-proline-4-nitroanilide. The peripheral mononuclear cells of pregnant women exhibited depressed mean dipeptidyl peptidase IV activity when compared with the activity of peripheral mononuclear cells from non-pregnant or male individuals. The gestational age (7 to 20 weeks) of the pregnant collective had no effects on peptidase levels. Women taking oral contraceptives had a slightly lower mean activity than the non-pregnant group not using contraceptives. Thus, reduced dipeptidyl peptidase IV activity of peripheral mononuclear cells might reflect impairement of cellular immunity during pregnancy.


Dynamic balancing of risks and rewards in a large herbivore: Further extending predator-prey concepts to road ecology.
Animal behaviour is shaped by the ability to identify risks and profitably balance the levels of risks encountered with the payoffs experienced. Anthropogenic disturbances like roads generate novel risks and opportunities that wildlife must accurately perceive and respond to. Basic concepts in predator-prey ecology are often used to understand responses of animals to roads (e.g. increased vigilance, selection for cover in their vicinity). However, prey often display complex behaviours such as modulating space use given varying risks and rewards, and it is unclear if such dynamic balancing is used by animals in the context of road crossings. We tested whether animals dynamically balance risks and rewards relative to roads using extensive field-based and GPS collar data from elk in Yoho National Park (British Columbia, Canada), where a major highway completely bisects their range during most of the year. We analysed elk behaviour by combining hidden Markov movement models with a step-selection function framework. Rewards were indexed by a dynamic map of available forage biomass, and risks were indexed by road crossings and traffic volumes. We found that elk generally selected intermediate and high forage biomass, and avoided crossing the road. Most of the time, elk modulated their behaviour given varying risks and rewards. When crossing the highway compared with not crossing, elk selected for greater forage biomass and this selection was stronger as the number of highway crossings increased. However, with traffic volume, elk only balanced foraging rewards when they crossed a single time during a travel sequence. Using a road ecology system, we empirically tested an important component of predator-prey ecology-the ability to dynamically modulate behaviour in response to varying levels of risks and rewards. Such a test articulates how decision-making processes that consider the spatiotemporal variation in risks and rewards allow animals to successfully and profitably navigate busy roads. Applying well-developed concepts in predator-prey theory helps understand how animals respond to anthropogenic disturbances and anticipate the adaptive capacity for individuals and populations to adjust to rapidly changing environments.


Modern Applications of Machine Learning in Shoulder Arthroplasty: A Review.
» There is increased integration of machine learning (ML) to aid clinical decision-making in orthopaedic surgery.» ML has the ability to predict both clinical outcomes such as range of motion and complications in total shoulder arthroplasty patients.» An increased area of focus is the ability for ML to identify implants to aid in revision surgery planning.» In this article, we review the current applications of ML in shoulder arthroplasty and discuss future areas where it may enhance orthopaedic practice.


Emergence of pandemic 2009 influenza A H1N1, India.
Pandemic H1N1 caused deluge of cases from 74 countries and prompted World Health Organization to raise warning to phase 6. The present study was conducted on throat and nasal swab samples received and tested at National Centre for Disease Control, Delhi, India during 2009-2010 to collect epidemiological and clinical information on positive cases. Throat and nasopharyngeal swabs from category C influenza A H1N1 patients during May 2009-September 2010 along with their clinico-epidemiological details were collected from identified hospitals from Delhi and other States. Samples were tested by Real time reverse transcriptase PCR using primers and probes developed at CDC, Atlanta for four influenza target genes. A total of 33,751 samples, both throat and nasal swab samples from each patient were tested for H1N1 influenza virus, of which, 7943 (23.5%) were positive for pandemic influenza A H1N1 and 3759 (11.1%) were positive for influenza A (seasonal flu). Maximum number of positive cases (N=2792, 35.1%) were from 20-39 yr age group, comprising 1790 (22.5%) males and 1182 (14.8%) females. Only 2620 (33%) positive cases were close contact of influenza A H1N1 positive patient. Majority cases presented (N=2792, 35.1%) with fever 7005 (88.1%), followed by 6133 cases (77.2%) exhibiting fever and cough, 377 (4.7%) complained of fever, cough, nasal catarrh and 362 (4.5%) cases had fever with shortness of breath. The study showed a peak of cases of pandemic influenza A H1N1 in December 2009 and indicated predominance of H1N1 positive cases among 20-39 yr age group and among males compared to females.


Characterization and expression of uterine and placental alkaline phosphatases in the mouse.
Alkaline phosphatase (ALP) is rapidly induced in the uterine subepithelial stroma after a natural or artificial decidual stimulus. During gestation ALP-specific activity peaked at Day 7 to 8 (Day 1 is day of detection of the copulation plug) followed by a rapid decline to control levels by Day 9. This elevation in enzyme activity was preceded by an 8-fold induction of a 2.6 kilobase (kb) mRNA. This mRNA was not preferentially localized to implantation sites. ALP activity was detected in the placenta at Day 9 and reached maximum specific activity at Day 19. The placental ALP was also encoded by a 2.6 kb mRNA. Uterine and placental ALPs were inhibited to the same extent by levamisole, L-tryptophan and homoarginine. The calculated Ki values for these inhibitors were not statistically different between the uterine and placental forms. Km values towards the substrate p-nitrophenylphosphate, however, were statistically different between the uterine and placental forms. Both uterine and placental ALPs were stimulated 3-4-fold by addition of 2 mM-Mg2+. Electrophoretic mobilities on SDS polyacrylamide gel, where the enzyme migrated as a single band, were the same. The uterine form, however, could be distinguished from the placental isoenzyme by separation on non-denaturing polyacrylamide gels; the uterine form had a single zone of activity which migrated with an intermediate mobility between the two zones of activity detected for the placental enzyme. These differences in mobility could be ascribed to the sialic acid content of the enzyme because treatment with neuraminidase resulted in the uterine and placental forms migrating with comparable but slower mobilities in non-denaturing gels.(ABSTRACT TRUNCATED AT 250 WORDS)


Lateral resolution enhancement of vertical scanning interferometry by sub-pixel sampling.
We apply common image enhancement principles and sub-pixel sample positioning to achieve a significant enhancement in the spatial resolution of a vertical scanning interferometer. We illustrate the potential of this new method using a standard atomic force microscope calibration grid and other materials having motifs of known lateral and vertical dimensions. This approach combines the high vertical resolution of vertical scanning interferometry and its native advantages (large field of view, rapid and nondestructive data acquisition) with important increases in lateral resolution. This combination offers the means to address a common challenge in microscopy: the integration of properties and processes that depend on, and vary as a function of observational length.


Spectral Imprints of Working Memory for Everyday Associations in the Frontoparietal Network.
How does the human brain rapidly process incoming information in working memory? In growing divergence from a single-region focus on the prefrontal cortex (PFC), recent work argues for emphasis on how distributed neural networks are rapidly coordinated in support of this central neurocognitive function. Previously, we showed that working memory for everyday "what," "where," and "when" associations depends on multiplexed oscillatory systems, in which signals of different frequencies simultaneously link the PFC to parieto-occipital and medial temporal regions, pointing to a complex web of sub-second, bidirectional interactions. Here, we used direct brain recordings to delineate the frontoparietal oscillatory correlates of working memory with high spatiotemporal precision. Seven intracranial patients with electrodes simultaneously localized to prefrontal and parietal cortices performed a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. First, task-induced oscillations in the same delta-theta (2-7 Hz) and alpha-beta (9-24 Hz) frequency ranges previously identified using scalp electroencephalography (EEG) carried information about the contents of working memory. Second, maintenance was linked to directional connectivity from the parietal cortex to the PFC. However, presentation of the test prompt to cue identity, spatial, or temporal information changed delta-theta coordination from a unidirectional, parietal-led system to a bidirectional, frontoparietal system. Third, the processing of spatiotemporal information was more bidirectional in the delta-theta range than was the processing of identity information, where alpha-beta connectivity did not exhibit sensitivity to the contents of working memory. These findings implicate a bidirectional delta-theta mechanism for frontoparietal control over the contents of working memory.


Surgical resection of an intradural extramedullary spinal tumor.
Large ventrally located spinal meningiomas are typically resected via a posterolateral or lateral approach. Optimal outcomes are associated with good preoperative functional status (i.e., modified McCormick grade < 4), while recurrence rates may be predicted by degree and quality of resection (i.e., low Simpson grade). This video describes the operative techniques for resection of a large ventral C2 intradural extramedullary meningioma in a 71-year-old male presenting with hemibody sensory loss and abnormal gait. A paramedian approach was performed, allowing for adequate exposure and gross-total resection. The patient was discharged on postoperative day 2 and showed near-complete resolution of sensory deficits.


Transplacental passage of vancomycin.
To evaluate a larger number of patients receiving a vancomycin-dosing regimen of 20 mg/kg IV every 8 h for Group B streptococcus (GBS) chemoprophylaxis and analyze maternal and neonatal cord blood levels at delivery. We prospectively enrolled every mother that entered labor with a positive GBS culture and a high-risk penicillin allergy with resistance to clindamycin or unknown sensitivity. Maternal and cord blood vancomycin levels were obtained at delivery. Time from last dose completion to delivery, number of doses administered and body mass index were assessed. A total of 30 patients consented and 23 (77%) maternal levels and cord blood levels were therapeutic. There were eight patients where one or both maternal and/or cord blood values were non-therapeutic, but in six of these, there was a regimen violation regarding timing of the next dose or total dosage administered. Of the 24 patients where the regimen was correctly followed, 22 (92%) had therapeutic maternal and cord blood levels. Using a vancomycin-dosing regimen of 20 mg/kg IV every 8 h (maximum individual dose of 2 g) produces therapeutic levels in more than 75% of mother/newborn pairs and this can exceed 90% when dosing regimens are correctly followed.


Thin films of conductive ZnO patterned by micromolding resulting in nearly isolated features.
Patterned and continuous thin films of conductive Al-doped zinc oxide (ZnO:Al) were prepared on different substrates from a polymeric precursor solution. Their electric conductivity and light transmittance (for visible and UV light) was measured at room temperature. By means of a simple device, conductive ZnO:Al films with high fidelity patterns with features of 2-20 microm width could be obtained by simply micromolding the liquid precursor film prior to heat treatment. The individual features were interconnected by a very thin residual ZnO layer.


Relative importance of charge neutralization and precipitation on coagulation of Kaolin with PACI: effect of sulfate ion.
The effect of the sulfate ion on coagulation with polyaluminum chloride (PACl) was investigated by using an optical monitoring technique together with the conventional jar test procedure and electrophoretic mobility (EM) measurements. The effect of the SO4(2-)/Al ratio, dosage, and pH were examined in detail. The experimental results show that sulfate has a significantly different effect on PACl coagulation as a result of preformed hydrolysis products, where charge neutralization and precipitation play different parts in the coagulation process. The increased rate of coagulation with increasing SO4(2-)/Al ratio can be partially explained by charge neutralization effects, through increased adsorption and complexation of sulfate, thus giving increased particle collision efficiency. Different PACl samples were prepared with different values of B ([OH]/[Al]). For B = 0 (i.e., AlCl3) with mainly monomers, hydroxide precipitation tends to be accelerated in the presence of sulfate, giving significant turbidity removal. The high charge neutralization ability remains for samples with B = 1.5 and 2.0, with large proportions of preformed oligomers and polymers. Sulfate promotes aggregation of hydrolyzed species for B= 2.5, causing significantly improved coagulation efficiency through an electrostatic patch effect. The results illustrate further that particle charge plays a less important role in coagulation after reaching a certain value, while precipitate formation improves coagulation significantly.


Expression patterns of claudins in patients with triple-negative breast cancer are associated with nodal metastasis and worse outcome.
Claudins (CLDNs) are key cell adhesion molecules, which compose tight junctions (TJs), and the disruption of TJs is associated with cancer development. Here we immunohistochemically studied expression patterns of CLDNs in 222 primary invasive breast cancers including 68 triple-negative breast cancers (TNBCs), and examined their correlation with epithelial-to-mesenchymal transition (EMT)-related markers, breast cancer stem cell (BCSC) markers, and clinicopathological features including patients' clinical outcome. Tumor margins were classified as three infiltrating growth patterns (expanding, intermediate and infiltrating). For CLDN1, 3, 4, and 7, their expression rates were more frequent in TNBCs than in other subtypes (11.8% vs 0.7%, 26.5% vs 2.0%, 48.5% vs 11.1%, and 32.4% vs 8.7%, respectively; P ≤ 0.001). In 68 TNBCs, we identified high Ki67 labeling index (LI) and the combination of CLDN4 high/CLDN7 low expression as independent predictors of axillary nodal metastasis (P = 0.019; OR, 4.36; 95%CI, 1.28-14.90 and P = 0.007; OR, 5.33; 95%CI, 1.58-17.90). Moreover, the combination of CLDN1 low/CLDN7 low/E-cadherin negative as well as tumor infiltrating patterns were predictors for worse recurrence-free survival by univariate analyses in TNBCs (P = 0.005 and P = 0.011). Our analyses provide further evidence that CLDNs would be valuable prognostic markers in TNBCs.


TAp73 promotes anabolism.
Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation.


Family functioning and children's adjustment: associations among parents' depressed mood, marital hostility, parent-child hostility, and children's adjustment.
Relations between parents' depressed mood, marital conflict, parent-child hostility, and children's adjustment were examined in a community sample of 136 ten-year-olds and their parents. Videotaped observational and self-report data were used to examine these relations in path analyses. A proposed model was tested in which mothers' and fathers' depressed mood and marital hostility were associated with children's adjustment problems through disruptions in parent-child relationships. Results showed that both mothers' and fathers' marital hostility were linked to parent-child hostility, which in turn was linked to children's internalizing problems. Fathers' depressed mood was linked to children's internalizing problems indirectly through father-child hostility. Fathers' depressed mood was directly linked to children's externalizing problems and indirectly linked through father-child hostility. For mothers, marital hostility was directly linked to children's externalizing problems, and marital hostility in fathers was indirectly linked to children's externalizing problems through father-child hostility.


A fermentor for study of sauerkraut fermentation.
A fermentor was designed and constructed for study of the physical, microbiological, and chemical changes that occur during the sauerkraut fermentation. The fermentor has some essential features that include restriction in volume of the sauerkraut bed, construction of clear plastic to permit visual determination of liquid-level changes as a result of gas entrapment within the sauerkraut bed, and a gas-lift device for use in nitrogen purging of the fermenting brine. Fermentations exhibited two distinct stages, the first one gaseous and the second non-gaseous. The gaseous stage was characterized by rapid CO(2) and acid production due to growth by hetero-fermentative lactic acid bacteria with resultant gas entrapment within the sauerkraut bed and a rise in liquid level. Also, rapid disappearance of fructose and rapid appearance of mannitol occurred during this stage. The nongaseous stage was characterized by growth of homo-fermentative lactic acid bacteria with little or no CO(2) production and a gradual increase in lactic acid until all fermentable sugars were metabolized. Nitrogen purging appeared to offer several potential advantages, including a means for brine circulation, removal of CO(2) from the brine, and anaerobiosis to ensure retention of ascorbic acid, desirable color, and other oxygen-sensitive traits in sauerkraut.


Classification of gait patterns in the time-frequency domain.
This paper describes the classification of gait patterns among descending stairs, ascending stairs and level walking activities using accelerometers arranged in antero-posterior and vertical direction on the shoulder of a garment. Gait patterns in continuous accelerometer records were classified in two steps. In the first step, direct spatial correlation of discrete dyadic wavelet coefficients was applied to separate the segments of gait patterns in the continuous accelerometer record. Compared to the reference system, averaged absolute error 0.387 s for ascending stairs and 0.404 s for descending stairs were achieved. The overall sensitivity and specificity of ascending stairs were 98.79% and 99.52%, and those of descending stairs were 97.35% and 99.62%. In the second step, powers of wavelet coefficients of 2 s time duration from separated segments of vertical and antero-posterior acceleration signals were used as features in classification. Our results proved a reliable technique of measuring gait patterns during physical activity.


[Global Health. Information for change. 4th report of the Italian Observatory on Global Health].
Global Health. Information for change. 4th report of the Italian Observatory on Global Health. InformAzione (InformAction) is the title of the last OISG report (Italian observatory on Global Health), dedicated to information and education, the essential bases for a conscious action aimed at decreasing inequalities. Increasing the investments in information, education and interventions oriented to global health may broaden the number of aware and informed citizens, able to start a dialogue, to make pressures to increase the interventions in favor of those in need.


Functional and structural optimization of the respiratory system of the bat Tadarida brasiliensis (Chiroptera, Molossidae): does airway geometry matter?
We studied structure and function of the respiratory system in the bat Tadarida brasiliensis and compared it with those of two species of rodents, Abrothrix andinus and A. olivaceus. Tadarida brasiliensis had lower resting oxygen consumption, but higher maximum oxygen consumption and aerobic scope, than the rodents. The blood-gas barrier of the bat was thinner and its relative lung size was larger; however, alveolar surface density was similar among the three species. In consequence, T. brasiliensis has an oxygen diffusion capacity two or three times higher than that of the rodents. In Tadarida brasiliensis the characteristics of the lung were accompanied by geometrical changes in the proximal airway, such as high physical optimization as a consequence of small variations in the symmetry and the scaling ratio of the bronchial diameters. These may constitute an efficient way to save energy in respiratory mechanics and are the first report of airway adjustments to decrease entropy generation in bats.


Thoracic laminectomy and midline myelotomy for resection of a spinal ependymoma.
Spinal cord ependymomas comprise 25% of all intramedullary tumors and are typically treated with resection. A man in his mid-60s presented with imbalance and sensory deficits in both lower extremities, and a spinal thoracic intramedullary ependymoma spanning the levels T2 and T3 was diagnosed. After a laminectomy was performed, the tumor was microsurgically resected, and the patient demonstrated no neurological deficits on postoperative examination. Subsequent MRI showed complete resection of the tumor. This video showcases a thoracic intramedullary ependymoma resected using careful microdissection into the median raphe as a safe entry zone to preserve neurological function.


Classical Anglican moral theology: unavoidably non-ecumenical.
In its specific moral conclusions ecclesiastical Anglican theology shares much with traditional Protestantism, Roman Catholicism, and Eastern Orthodoxy. In its understanding of the method and purpose of moral theology classical Anglicanism sometimes diverges from earlier Roman Catholicism -- and anticipates the most positive developments in contemporary Roman Catholic moral theology -- while sharing a common theological heritage with Rome in its understanding of natural law, the moral agent, and the moral act. Anglicans situate moral reasoning within the Church of the patristic Tradition, which distinguishes them from Protestants, yet do not accept the Roman magisterium's self-understanding. Consequently, the Anglican mode of moral reasoning has strong affinities with the Orthodox churches.


Physiological implications of COVID-19 in reproduction: angiotensin-converting enzyme 2 a key player.
The COVID-19 outbreak, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was first identified in China, and it has quickly become a global threat to public health due to its rapid rate of transmission and fatalities. Angiotensin-converting enzyme 2 (ACE2) has been identified as a receptor that mediates the entry of SARS-CoV-2 into human cells, as in the case of severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have reported that ACE2 expression is higher in Leydig, Sertoli and seminiferous ductal cells of males, as well as in ovarian follicle cells of females, suggesting possible potential pathogenicity of the coronavirus in the reproductive system. Higher ACE2 expression in the human placenta and reports of vertical transmission of SARS-CoV-2 among clinical cases have increased the relevance of further studies in this area. This review focuses on the interaction between SARS-CoV-2 and the ACE2 receptor and speculates on the mechanistic interplay in association with male and female reproductive physiology. In addition, based on the available literature, we discuss the alleged sex differences in terms of the infectivity of SARS-CoV-2, which is claimed greater among males, and further explore the physiological role of ACE2 and 17β-oestradiol for the same.


High-resolution mapping of genes involved in plant stage-specific partial resistance of barley to leaf rust.
Partial resistance quantitative trait loci (QTLs) Rphq11 and rphq16 against Puccinia hordei isolate 1.2.1 were previously mapped in seedlings of the mapping populations Steptoe/Morex and Oregon Wolfe Barleys, respectively. In this study, QTL mapping was performed at adult plant stage for the two mapping populations challenged with the same rust isolate. The results suggest that Rphq11 and rphq16 are effective only at seedling stage, and not at adult plant stage. The cloning of several genes responsible for partial resistance of barley to P. hordei will allow elucidation of the molecular basis of this type of plant defence. A map-based cloning approach requires to fine-map the QTL in a narrow genetic window. In this study, Rphq11 and rphq16 were fine-mapped using an approach aiming at speeding up the development of plant material and simplifying its evaluation. The plant materials for fine-mapping were identified from early plant materials developed to produce QTL-NILs. The material was first selected to carry the targeted QTL in heterozygous condition and susceptibility alleles at other resistance QTLs in homozygous condition. This strategy took four to five generations to obtain fixed QTL recombinants (i.e., homozygous resistant at the Rphq11 or rphq16 QTL alleles, homozygous susceptible at the non-targeted QTL alleles). In less than 2 years, Rphq11 was fine-mapped into a 0.2-cM genetic interval and a 1.4-cM genetic interval for rphq16. The strongest candidate gene for Rphq11 is a phospholipid hydroperoxide glutathione peroxidase. Thus far, no candidate gene was identified for rphq16.