Enzymatic Synthesis of Homogeneous Chondroitin Sulfate Oligosaccharides.
Chondroitin sulfate (CS) is a sulfated polysaccharide that plays essential physiological roles. Here, we report an enzyme-based method for the synthesis of a library of 15 different CS oligosaccharides. This library covers 4-O-sulfated and 6-O-sulfated oligosaccharides ranging from trisaccharides to nonasaccharides. We also describe the synthesis of unnatural 6-O-sulfated CS pentasaccharides containing either a 6-O-sulfo-2-azidogalactosamine or a 6-O-sulfogalactosamine residue. The availability of structurally defined CS oligosaccharides offers a novel approach to investigate the biological functions of CS.


Controlled release of tetracycline hydrochloride from poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin nanofibers.
Development of drug delivery systems is an extensively researched area in biomedical field. In recent years, there is an increasing interest on fabrication of biocompatible nanofibrous drug delivery systems. In the present study, poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin nanofibrous membranes were fabricated for the controlled delivery and release of tetracycline hydrochloride (TCH) antibiotic. Poly(ω-pentadecalactone-co-ε-caprolactone) content provides an originality to the membrane, since it has been synthesized enzymatically previously. Varied amounts of tetracycline hydrochloride including poly(ω-pentadecalactone-co-ε-caprolactone)/gelatin (1:1, v:v) binary polymer blend was electrospun and characterizations (morphological and molecular structure, wettability characteristics, and thermal behavior) were applied to investigate the incorporation of drug molecule. Afterwards, in vitro drug release studies were carried out and mathematical modelling was applied to drug release data in order to clarify the transport mechanism of drug. TCH release profile comprised of an initial burst release in first hour and followed by a sustained release through 14 days which allowed sufficient antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. The presented drug delivery system may be applied as an antibacterial wound dressing device for skin infections.


The recurrence spectra of Rydberg HeH+ molecule ion in a magnetic field.
Making use of the molecular closed-orbit theory and a new model potential for the Rydberg molecule, we calculated the recurrence spectra of HeH(+) molecule ion in a magnetic field for different quantum defects. The Fourier transformed spectra of HeH(+) molecule ion have allowed direct comparison between peaks in the spectra and the scaled action values of closed orbits of the excited electron in the external fields. We find that the spectral modulations can be analyzed in terms of the scattering of the excited electron on the molecular core. Unlike the case of the Rydberg atom where the elastic scattering is predominant, modulations produced by inelastic scattering are also vital to the photoabsorption spectrum of Rydberg molecule. Our results are in good agreement with the quantum results, which suggest that our method is correct.


Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells.
This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion.


Field exercise testing for assessing fitness in French standardbred trotters.
This review considers standardized exercise testing which is, routinely used for French Trotters in the field. Track testing provides a more limited range of measurements than treadmill testing, but has the advantage of being performed in the horse's natural environment. Various measurements such as heart rate during exercise and blood lactate concentration after exercise may be measured on the track and lead to the calculation of physiological variables such as V200 (velocity corresponding to a 200 bpm heart rate) and V4 (velocity corresponding to a 4 mmol/L blood lactate concentration). V4 is related to the onset of blood lactate accumulation and relates to the aerobic capacity of the horse, as horses with high values for V4 have higher aerobic capacities. Although V4 is calculated during submaximal intensity exercise, it is related to racing performance and seems to be the most important measurement to assess changes in fitness. V200 represents the cardiac capacity of the horse during exercise and is close to V4 in mature horses. To explain further the clinical usefulness of track testing, and to help interpret both V4 and V200 variables, examples of exercise tests in 3-year-old French Trotters are presented here. These results show that changes may occur in V4 and V200 according to different factors such as the horse's physical ability and either training or disease states. It underlines the importance of exercise tests for both trainers and veterinarians and how they may help in the evaluation of a horse's performance ability; in defining the intensity of a training program, and also in the early detection of underlying diseases.


Adapting an Effective Counseling Model from Patient-centered Care to Improve Motivation in Clinical Training Programs.
The value of establishing a patient-centered relationship within the context of the clinical encounter is well documented. The learner-centered method of medical education parallels the patient-centered clinical method; therefore, it should be explored as a method for teaching in the context of the learning encounter. In Japan and other Asian countries, rotations through services not related to the learner's chosen medical specialty are mandatory parts of the medical internship. Participation and effort in these rotations are often met with resistance from learners and are a common problem for medical educators. We adapted the counseling method for patients based on patient-centered methods such as motivational interviewing and solution-focused therapy to address this common problem. We show one case of a medical resident who lost his motivation to learn during his training. A resident has many kinds of mental and physical stress. One such problem arises from the gap between what they want to do and what they have to do. Strategies from motivational interviewing and solution-focused therapy were adapted to successfully resolve a common teaching problem in Japan. A physician teacher (preceptor) helped this resident solve the issue for himself instead of arguing in favor of change. The positive aspects of the counseling method were based on patient-centered medicine and proved useful and effective in counseling for medical residents. We may take the lessons learned from using patient-centered counseling methods to further develop a clear and systematic process of counseling methods for residents to conduct learner-centered medical education.


[The cardiotoxicity of bupivacaine during pacemaker stimulation is dependent on the stimulation frequency. Results of an experimental study].
The cardiotoxic effects of bupivacaine are related to the temporal dispersion of effective refractory periods in different parts of the cardiac conduction system. This effect facilitates the occurrence of re-entry arrhythmias under burst stimulation [4, 8]. In this study physiological increments in heart rate were simulated by cardiac pacing, and the electrophysiological and haemodynamic effects under the influence of cardiotoxic concentrations of bupivacaine were measured. METHODS. After institutional approval we generated cardiotoxic arterial plasma concentrations of bupivacaine (6.9 +/- 1.6 micrograms/ml) in pigs (n = 8; 15-22 kg) by i.v. injection of 4 mg bupivacaine/kg, followed by a constant rate infusion of 0.2 mg/kg per min [8]. The pigs were anaesthetized with midazolam, fentanyl and pancuronium and normoventilated with a FiO2 of 0.4. Internal right atrial and right ventricular pacing was performed with increasing frequencies of 20, 40, 60, 80 and 100 stimulations/min above individual spontaneous heart rates (AL) before (control) and after the administration of bupivacaine. ECG, MAP, LVSP, dp/dtmax and stimulation thresholds were recorded. Student's t-test, and the U-test of Wilcoxon, Mann and Whitney were used for statistical testing with a significance level of 0.05. RESULTS. By inducing a frequency-dependent increase in stimulation threshold, bupivacaine prevented regular atrial pacing with frequencies higher than AL + 60. Ventricular pacing with a frequency of AL+40 induced a lethal arrhythmia in 1 animal. In the remaining 7 pigs ventricular pacing showed a frequency-dependent increase in stimulation thresholds (Fig. 1) and stimulus-QRS intervals (Fig. 5). MAP (Fig. 2), LVSP (Fig. 3) and cardiac inotropy (Fig. 4) showed frequency-dependent decreases under ventricular pacing. CONCLUSIONS. The toxic effects of bupivacaine on pacing thresholds, av conduction, intraventricular conduction, cardiac inotropy, and blood pressure are modulated by the stimulation frequency of a cardiac pacemaker. The cardiotoxic effects of bupivacaine seem to be use dependent. Even minor increments in heart rate can induce malignant arrhythmias. Cardiac pacing can be difficult in the presence of toxic bupivacaine concentrations, and high-frequency pacing should be avoided. It has to be verified whether higher heart rates generated by the physiological pacemakers of the heart do also increase the cardio-circulatory toxicity of bupivacaine. If that holds true, drugs that can induce tachycardias should be avoided in the treatment of bupivacaine toxicity.


Sorghum and wheat differentially affect caecal microbiota and associated performance characteristics of meat chickens.
This study compared the effects of wheat- and sorghum-based diets on broiler chickens. The growth performance and caecal microbial community of chickens were measured and correlations between productivity and specific gut microbes were observed. Cobb broilers 15 days of age were individually caged and two dietary treatments were used, one with a wheat-based diet (n = 48) and another one with a sorghum-based diet (n = 48). Growth performance measurements were taken over a 10 day period and samples for microbiota analysis were taken at the end of that period. Caecal microbiota was characterised by sequencing of 16S bacterial rRNA gene amplicons. Overall, the results indicated that a sorghum-based diet produced higher apparent metabolisable energy (AME) and body-weight gain (BWG) values in chickens, compared to a wheat-based diet. Nevertheless, sorghum-fed birds had higher feed conversion ratio (FCR) values than wheat-fed birds, possibly because of some anti-nutritional factors in sorghum. Further analyses showed that caecal microbial community was significantly associated with AME values, but microbiota composition differed between dietary treatments. A number of bacteria were individually correlated with growth performance measurements. Numerous OTUs assigned to strains of Lactobacillus crispatus and Lachnospiraceae, which were prevalent in sorghum-fed chickens, were correlated with high AME and BWG values, respectively. Additionally, a number of OTUs assigned to Clostridiales that were prevalent in wheat-fed chickens were correlated with low FCR values. Overall, these results suggest that between-diet variations in growth performance were partly associated with changes in the caecal microbiota.


Reactivity of Ti(IV) species hosted in TS-1 towards H2O2-H2O solutions investigated by ab initio cluster and periodic approaches combined with experimental XANES and EXAFS data: a review and new highlights.
This work is intended to underline how the most-advanced experimental and theoretical physical chemistry tools must be used synergistically to understand the reactivity of Ti-silicalite-1 (TS-1) in an important number of low-temperature oxidation reactions with aqueous H(2)O(2) as the oxidant. Literature results are carefully reviewed and accompanied with new, unpublished highlights of both experimental and computational origin. The first part of this work is devoted to a discussion of the defective nature of the material and to the synergic role played by Si vacancies and Ti insertion in the framework. A summary of the experimental Ti-K-edge EXAFS and XANES literature concerning the activated material in vacuo conditions is then presented and compared to the corresponding Ti geometries obtained by ab initio calculations. From such a comparison, the excellent agreement between experiment and theory is evident. A very good agreement is also obtained for the interaction with water and ammonia. For both H(2)O and NH(3), the agreement is due to the possibility to perform experiments in which the probe molecule is dosed from the gas phase, thus allowing to reach the 1 : 1 (or 1 : 2) ratio between the adsorbing Ti sites and the adsorbed molecule. Then, interaction with hydrogen peroxide is discussed, underlining the problems faced in reaching a common view between experimental and theoretical results, owing to the difficulties both in performing experiments where anhydrous H(2)O(2) is dosed on TS-1, and in taking into account the role played by the aqueous medium in the reactivity of Ti(iv) centres toward H(2)O(2) using ab initio calculations. Only once such difficulties have been overcome, by increasing the complexities of both experiments and ab initio models, is a joint-view finally obtained. Where needed, comparison with other experimental results (X-ray and neutron diffraction, NMR, IR, Raman, UV-vis and resonant Raman) is made.


Human neutrophils mediate trogocytosis rather than phagocytosis of CLL B cells opsonized with anti-CD20 antibodies.
Polymorphonuclear neutrophils (PMNs) have previously been reported to mediate phagocytosis of anti-CD20-opsonized B cells from patients with chronic lymphocytic leukemia (CLL). However, recent data have suggested that PMNs, like macrophages, can also mediate trogocytosis. We have performed experiments to more precisely investigate this point and to discriminate between trogocytosis and phagocytosis. In live-cell time-lapse microscopy experiments, we could not detect any significant phagocytosis by purified PMNs of anti-CD20-opsonized CLL B cells, but could detect only the repeated close contact between effectors and targets, which suggested trogocytosis. Similarly, in flow cytometry assays using CLL B-cell targets labeled with the membrane dye PKH67 and opsonized with rituximab or obinutuzumab, we observed that a mean of 50% and 75% of PMNs had taken a fraction of the dye from CLL B cells at 3 and 20 hours, respectively, with no significant decrease in absolute live or total CLL B-cell numbers, confirming that trogocytosis occurs, rather than phagocytosis. Trogocytosis was accompanied by loss of membrane CD20 from CLL B cells, which was evident with rituximab but not obinutuzumab. We conclude that PMNs mediate mostly trogocytosis rather than phagocytosis of anti-CD20-opsonized CLL B cells, and we discuss the implications of this finding in patients with CLL treated with rituximab or obinutuzumab in vivo.


Microfracture patterns of abrasive wear striations on teeth indicate directionality.
A method is described that will indicate the direction that an abrasive particle was traveling as it scored the surface of a brittle material. Light and scanning electron micrographs of glass, dentine, and enamel abraded by loose and, steel carbide, and diamond indicate that partial Hertzian fracture cones are formed at the margins of wear striations during abrasion. The bases of these fracture cones face in the direction of travel of the abrasive particle and, therefore, indicate directionality. Because this method is based only on the consistent geometry of fracturing of brittle materials, it is independent of the loading of the abrasive particle. The only other method available to determine directionality of striations is unreliable since it uses the width of striations, and, hence, is dependent upon a consistent loading regime of the abrasive particle. This new method has direct application for determining the direction of movement of the jaws during mastication in living or fossil animals.


[Equity of Health Resources Allocation in Minority Regions of Sichuan Province].
To determine equity of health resources allocation in minority regions of Sichuan province from 2009 to 2013. Health resources distribution equity among populations and across geographic catchments were measured using coefficients of Inter-Individual differences and Individual-Mean differences. Health resources, especially human resources, in minority regions increased slowly over the years. Poorer allocation equity was found in nursing resources compared with doctors and hospital beds. Better distribution equity was found among populations than across geographic catchments. High levels of equity in resource distributions among populations and across geographic catchments were found in Aba. In Liangshan, more equitable distributions were found in doctors and hospital beds compared with nurses. The rest of minority regions had poor absolute allocation equity in doctors and hospital beds among populations. Appropriate allocation of health resources can promote health development. Health resources allocation in minority regions of Sichuan province is unreasonable. The government and relevant departments should take actions to optimize health resources allocations.


Investigation of population-based mental health staffing and efficiency-based mental health productivity using an information-theoretic approach.
Healthcare systems monitor and improve mental health treatment quality, access, continuity and satisfaction through use of population-based and efficiency-based staffing models, the former focused on staffing ratios and the latter, staff productivity. Preliminary evidence suggests that both high staffing ratios and moderate-to-high staff productivity are important for ensuring a full continuum of mental health services to indicated populations. With an information-theoretic approach, we conducted a longitudinal investigation of mental health staffing, productivity and treatment at the largest integrated healthcare system in American, the Veterans Health Administration (VHA). VHA facilities (N = 140) served as the unit of measure, with mental health treatment quality, access, continuity and satisfaction predicted by facility staffing and productivity in longitudinal mixed models. An information-theoretic approach: (a) entails the development of a comprehensive set of plausible models that are fit, ranked and weighted to quantitatively assess the relative support for each, and (b) accounts for model uncertainty while identifying best-fit model(s) that include important and exclude unimportant explanatory variables. In best-fit models, higher staffing was the strongest and most consistent predictor of better treatment quality, access, continuity and satisfaction. Higher staff productivity was often, but not always associated with better treatment quality, access, continuity and satisfaction. Results were further nuanced by differential prediction of treatment by between- and within-facility predictor effects and variable interactions. A population-based mental health staffing ratio and an efficiency-based productivity value are important longitudinal predictors of mental health treatment quality, access, continuity and satisfaction. Our longitudinal design and use of mixed regression models and an information-theoretic approach addresses multiple limitations of prior studies and strengthen our results. Results are discussed in terms of the provision of mental health treatment by healthcare systems, and analytical modeling of treatment quality, access, continuity and satisfaction.


Acute kidney injury in preterm neonates with ≤30 weeks of gestational age and its risk factors.
Acute kidney injury (AKI), an abrupt decline in kidney function, is a challenging diagnosis among preterm infants due to some specific features of this population. The aim of this study was to determine the risk factors of developing AKI and the predictive factors for its severity in preterm neonates with less than 31 weeks of gestational age. All neonates with less than 31 weeks of gestational age, admitted in our NICU between January 2012 and December 2015, were included. Maternal and neonatal records about demographics, placental abnormalities, perinatal and neonatal period and evolution in NICU, as well as electrolytic analysis and serum creatinine and urea values during their hospitalization were retrospectively collected and analyzed. A total of 106 neonates were included. Of those, 24 were diagnosed with AKI, resulting in a prevalence of 22.6%, and 82 were used as controls. Gestational age (OR=0.39; 95% CI=0.2-0.76; P=0.006), congenital malformations (OR=36.93; 95%CI=2.48-550.59; P=0.009), vasoactive drugs (OR=27.06; 95%CI=3.58-204.45; P=0.001), nonsteroidal anti-inflammatory drugs (OR=9.61; 95%CI=1.78-51.73; P=0.008) and sepsis (OR=7.78; 95%CI=1.32-46.04; P=0.024) were found to be independent risk factors. Cardiac surgery was a predictive factor for AKI severity (OR=25; 95%CI=2.09-298.29; P=0.011). The mortality rate in the AKI group was 41.7%. AKI in preterm neonates is an important feature that contributes to increase the mortality in NICUs. Thus, it is crucial to know its risk factors to establish prompt diagnosis and prevention and, in this way, be able to improve the prognosis.


The effect of microbial phytase and myo-inositol on performance and blood biochemistry of broiler chickens fed wheat/corn-based diets.
A total of 1,200 Ross broiler chickens were used in 2 separate feeding studies to explore the effect of myo-inositol (MYO) and phytase on performance and blood biochemistry of broilers fed diets formulated to be either adequate or insufficient in Ca and digestible P (dP). Supplementation of diets that were formulated to be insufficient in Ca and dP with MYO resulted in improved BW gain and feed conversion ratio in both experiments. However, these effects were most pronounced in the finisher phase, and moderate negative effects were observed during the starter period. Supplementation of the diet with microbial phytase improved BW gain and feed conversion ratio to a similar extent as was observed with MYO, and there was a degree of subadditivity between the 2 additives. Blood glucose concentrations were increased by both MYO and phytase, though possibly by different mechanisms, because insulin concentrations were not directly relatable to circulating glucose levels, especially when both MYO and phytase were applied simultaneously. The increase in blood glucose concentrations with MYO and phytase was most pronounced in the diet with a lower Ca and dP concentration. It can be concluded that dietary supplementation with MYO or phytase was effective in improving performance of commercial broiler chickens. However, further work is required to explore complex ontogenetic effects of MYO and possible involvement of both MYO and phytase in Na-dependent transport mechanisms.


Surgical treatment of the 'slipping rib syndrome'.
This review seeks to draw attention to the existence of the 'slipping rib syndrome' as a not uncommon clinical entity. It is characterized by trunk pain in a radicular distribution, often related to certain movements or activity, but not associated with other visceral symptoms. The diagnosis is a clinical one, with surgical excision of the affected rib and costal cartilage a successful simple treatment for relieving those patients of a severe and persistent pain syndrome.


Study on Photochemical Properties of a Sr-SnS2/CaIn2S4 Heterostructure to Improve Cr(VI) Removal.
Compound semiconductor photocatalysis technology is considered to be a promising treatment for solving water problems efficiently. The point of designing high-efficiency catalysts is to optimize the band gap structure and facilitate the separation of charge carriers by establishing new electron migration pathways. Recently, 3D porous CaIn2S4 was found to have good photocatalytic ability. However, the quick recombination and agglomeration of carriers still limit its application. Herein, we prepared a heterostructure by introducing 2D Sr-doped SnS2 to 3D CaIn2S4 by a hydrothermal synthesis method. The optimal dosage of Sr-SnS2 is 3%, and the photocatalytic Cr(VI) removal efficiency of 3% Sr-SnS2/CaIn2S4 (SSCS-3) is 5.82 and 10.83 times those of pure CaIn2S4 and SnS2, respectively. According to the results of characterization tests and calculation verification, we inferred that the enhanced photocatalytic removal of Cr(VI) is due to the introduction of Sr-SnS2 that can promote the rapid transfer of photogenerated electrons to the surface of CaIn2S4, and the heterostructure formed between 2D Sr-SnS2 and 3D CaIn2S4 can also provide abundant reaction sites. The promotion of carrier separation is mainly due to the formation of a built-in electric field of the Sr-SnS2/CaIn2S4 heterostructure. This work provides new ideas and technologies for the treatment of Cr(VI) in wastewater.


Efficacy of zidovudine compared to stavudine, both in combination with lamivudine and indinavir, in human immunodeficiency virus-infected nucleoside-experienced patients with no prior exposure to lamivudine, stavudine, or protease inhibitors (novavir trial).
We compared the efficacy and the toxicity of zidovudine (AZT) versus stavudine (d4T), in combination with lamivudine (3TC) and indinavir, in AZT-, dideoxyinosine (ddI)-, and/or dideoxycytosine (ddC)-experienced patients in a randomized comparative multicenter trial. One hundred seventy human immunodeficiency virus type 1 (HIV-1)-infected patients, who had received AZT, ddI, and/or ddC for at least 6 months but were naive for d4T, 3TC, and protease inhibitors, were randomized to AZT at 250 to 300 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h or to d4T at 40 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h. The primary endpoint was time to virological failure, defined as plasma HIV-1 RNA levels of >5,000 copies/ml after at least 8 weeks of antiretroviral therapy. Additional endpoints were change from baseline in CD4 cell counts, AIDS-defining events and adverse events, and proportion of patients with HIV-1 RNA levels of <500 copies/ml and HIV-1 RNA levels of <50 copies/ml. At week 80, 15 patients in the AZT arm and 14 patients in the d4T arm had reached the primary endpoint, and time to virological failure did not differ between the two arms (P = 0.98). In the d4T and in the AZT arms, 67 and 73% of patients, respectively, had HIV-1 RNA levels of <500 copies/ml (P = 0.50). The median change from baseline in CD4 cell count was 195 x 10(6) and 175 x 10(6)/liter for the d4T- and AZT-containing arms, respectively. The proportions of patients with HIV-1 RNA levels of <50 copies/ml at weeks 8, 16, and 24 were similar in the two arms. The occurrence of serious adverse events was not significantly different between arms. In conclusion, in these patients heavily pretreated with AZT, switching from AZT to d4T when initiating indinavir and 3TC did not bring any additional benefit compared to maintaining AZT.


Current status and future directions for diagnostic markers of drug-induced vascular injury.
Recently, there has been an increased incidence of vascular toxicity in pre-clinical toxicology studies. This is of concern because of the uncertain relevance and extrapolation of this finding to humans. In dogs, profound heart rate (HR) and mean arterial pressure (MAP) changes were considered surrogate markers for drug-induced vascular injury until the early 1990s when endothelin receptor antagonists (ETRA) did not significantly alter HR or MAP but induced identical lesions in the coronary arteries of dogs. Thus significant alterations in HR and MAP were found not to be a prerequisite for this lesion. Clinically, the potential for vascular injury coupled with the lack of an unequivocal non-invasive diagnostic marker is an issue of concern to pharmaceutical companies and the regulatory authorities. Therefore, qualification and validation of biomarkers as diagnostic tools for drug-induced vascular injury would add great value to risk management and expedite the drug development process. This review focuses on the status, progress and future trends in vascular biology aimed at identification and development of diagnostic markers that are specific, sensitive and possess potential utility in both a pre-clinical and clinical setting.


Effects of temperature on the carbonation of flue gas desulphurization gypsum using a CO2/N2 gas mixture.
The carbonation of flue gas desulphurization (FGD) gypsum using a CO2/N2 gas mixture was investigated to study the feasibility of using the flue gas directly in the gypsum carbonation. The effect of the reaction temperature on the carbonation reaction and the carbonation conversion efficiency of the samples were considered. In this study, the carbonation conversion efficiency was calculated using a new method for decreasing the error range from a sample containing unreacted gypsum. The carbonation reaction at 40°C was nearly twice as fast as the reaction at room temperature. In addition, the carbonation conversion efficiency at 40°C (96%) was nearly the same as that at room temperature. However, the efficiency decreased significantly with temperature, especially above 60°C. It can, therefore, be concluded that the direct use of flue gas in gypsum carbonation is most feasible at 40°C. The temperature of carbonation strongly affected the CaCO3 polymorphs and the morphological characteristics. Calcite with various shapes was the dominant (40-90%) phase at all temperatures. At temperatures below 40°C, spherical-shaped vaterite was pronounced, while needle-flower-shaped aragonite was dominant at temperatures above 80°C.


Phylogenetic relationships and divergence dates of softshell turtles (Testudines: Trionychidae) inferred from complete mitochondrial genomes.
The softshell turtles (Trionychidae) are one of the most widely distributed reptile groups in the world, and fossils have been found on all continents except Antarctica. The phylogenetic relationships among members of this group have been previously studied; however, disagreements regarding its taxonomy, its phylogeography and divergence times are still poorly understood as well. Here, we present a comprehensive mitogenomic study of softshell turtles. We sequenced the complete mitochondrial genomes of 10 softshell turtles, in addition to the GenBank sequence of Dogania subplana, Lissemys punctata, Trionyx triunguis, which cover all extant genera within Trionychidae except for Cyclanorbis and Cycloderma. These data were combined with other mitogenomes of turtles for phylogenetic analyses. Divergence time calibration and ancestral reconstruction were calculated using BEAST and RASP software, respectively. Our phylogenetic analyses indicate that Trionychidae is the sister taxon of Carettochelyidae, and support the monophyly of Trionychinae and Cyclanorbinae, which is consistent with morphological data and molecular analysis. Our phylogenetic analyses have established a sister taxon relationship between the Asian Rafetus and the Asian Palea + Pelodiscus + Dogania + Nilssonia + Amyda, whereas a previous study grouped the Asian Rafetus with the American Apalone. The results of divergence time estimates and area ancestral reconstruction show that extant Trionychidae originated in Asia at around 108 million years ago (MA), and radiations mainly occurred during two warm periods, namely Late Cretaceous-Early Eocene and Oligocene. By combining the estimated divergence time and the reconstructed ancestral area of softshell turtles, we determined that the dispersal of softshell turtles out of Asia may have taken three routes. Furthermore, the times of dispersal seem to be in agreement with the time of the India-Asia collision and opening of the Bering Strait, which provide evidence for the accuracy of our estimation of divergence time. Overall, the mitogenomes of this group were used to explore the origin and dispersal route of Trionychidae and have provided new insights on the evolution of this group.


Levels of Anti-Retinal Antibodies in Retinal Detachment and Proliferative Vitreoretinopathy.
The purpose of the study is to investigate the correlation between intraocular anti-retinal antibodies and clinical measurements in patients with rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinopathy (PVR). Aqueous humor and vitreous samples were collected from patients with RRD, PVR, and from control subjects with macular hole. The levels of total protein (TP), IgG, and anti-retinal antibodies were determined with a bicinchoninic acid assay, enzyme-linked immunosorbent assay, and dot blot, respectively. Correlations between these measurements were assessed using Pearson's correlation test. Analysis of variance followed by a post-hoc test or the Student t-test was used to compare differences between groups. The levels of anti-retinal antibodies and IgG were correlated with each other (P < 0.010). The IgG concentration was higher in patients with PVR than in controls in both the aqueous humor (P < 0.001) and the vitreous (P < 0.001), but not in patients with RRD. Conversely, TP levels and anti-retinal antibodies in both ocular fluids from RRD and PVR patients did not significantly differ from the controls. In a subgroup analysis, vitreal anti-retinal antibody levels were correlated with average macular thickness in the re-attached macula following surgery for macula-off RRD/PVR (P = 0.012). Furthermore, patients with post-operative cystoid macular edema had a higher level of vitreal anti-retinal antibodies than those without (P = 0.009). Intravitreal anti-retinal antibodies were increased in the eyes with maculopathy after surgical intervention for RRD/PVR.


Is ovulation induction with letrozole in breast cancer patients still safe even if it could increase progesterone levels?
Very high progesterone levels (mean 186.6 ± 43.6 ng/mL) during the luteal phase were found in a small study of breast cancers patients undergoing controlled ovarian stimulation (COS) with letrozole plus recombinant FSH. Results highlight the need to further evaluate this in larger series. While waiting, the clinical significance of high progesterone levels can be drawn from epidemiological and experimental data here reviewed in order to give reassurance to the clinician involved in fertility preservation. If the progesterone increase will be confirmed, epidemiological and experimental data do not seem to indicate a detrimental effect or they could even be protective. As this possible rise of levels is a very short event in the very long lasting and multifactorial breast carcinogenesis, it is unlikely that it will significantly influence breast cancer prognosis.


Confirmation of quark-hadron duality in the neutron F2 structure function.
We apply a recently developed technique to extract for the first time the neutron F(2)(n) structure function from inclusive proton and deuteron data in the nucleon resonance region, and test the validity of quark-hadron duality in the neutron. We establish the accuracy of duality in the low-lying neutron resonance regions over a range of Q(2), and compare with the corresponding results on the proton and with theoretical expectations. The confirmation of duality in both the neutron and proton opens the possibility of using resonance region data to constrain parton distributions at large x.


Cough and alterations in semen after a tropical swim.
This case report describes a patient with cough and haematospermia shortly after visiting a Schistosoma endemic area. Numerous S. haematobium eggs were found in the ejaculate, while no eggs were seen in the urine.


Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity.
The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4(+)SNS-Cre/TdTomato(+), 2) IB4(-)SNS-Cre/TdTomato(+), and 3) Parv-Cre/TdTomato(+) cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation.


The Association of Individual and Regional Socioeconomic Status on Initial Peritonitis and Outcomes in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Study.
♦ Research indicates that the socioeconomic status (SES) of individuals and the area where they live are related to initial peritonitis and outcomes in peritoneal dialysis (PD). We conducted a retrospective, multi-center cohort study in China to examine these associations. ♦ Data on 2,171 PD patients were collected from 7 centers, including baseline demographic, socioeconomic, and laboratory data. We explored the potential risk factors for initial peritonitis and outcomes using univariate Cox regression and unadjusted binary logistic regression. Then, we used propensity score matching to balance statistically significant risk factors for initial peritonitis and outcomes, and Kaplan-Meier survival analysis to compare differences in peritonitis-free rates between different groups of participants after matching. ♦ A total of 563 (25.9%) initial episodes of peritonitis occurred during the study period. The Kaplan-Meier peritonitis-free rate curve showed high-income patients had a significantly lower risk than low-income patients (p = 0.007) after matching for age, hemoglobin, albumin, and regional SES and PD center. The risk of treatment failure was significantly lower in the high-income than the low-income group after matching for the organism causing peritonitis and PD center: odds ratio (OR) = 0.27 (0.09 - 0.80, p = 0.018). Regional SES and education were not associated with initial peritonitis and outcomes. ♦ Our study demonstrates low individual income is a risk factor for the initial onset of peritonitis and treatment failure after initial peritonitis.


Characterization of the antiviral activity produced during Trypanosoma cruzi infection and protective effects of exogenous interferon against experimental Chagas' disease.
Mice infected with Trypanosoma cruzi have been shown to develop an antiviral activity in their sera as early as 24 hr postinfection. This activity was characterized in this work as alpha/beta interferon by the following criteria: resistance to pH 2 treatment, sensitivity to incubation at 56 C, or to trypsin treatment, or to actinomycin D treatment, and inactivation by antibody specific for alpha/beta interferon produced in L cells. Mice receiving exogenous alpha/beta interferon in seven daily doses starting on the day of infection with T. cruzi displayed an enhanced resistance evidenced by significantly decreased parasitemias with respect to those of infected animals receiving a mock preparation lacking interferon activity. Direct incubation of T. cruzi with interferon had no consequence on the motility, infectivity or virulence of the parasite. These results suggest a possible role for interferon in inducing enhancement of host resistance against T. cruzi infection.


Need for In Vivo Triggering of Homeostasis to Repair Irreversible Tissue Degeneration by Stem Cells through Innate and Invasive Regeneration Processes.
The regeneration patterns are innate, inherited and evolutionarily conserved mechanisms. In every individual there are certain cells and signaling networks which work together to proliferate the desired tissue lineages to replace the dead, lost and injured counter parts. This homeostasis mechanism keeps functioning of the organ system intact. There are some tissues such as skin, gut, blood, respiratory tract, uterine endometrium, testis must perpetually renew the majority of cells. As the aging advances the turnover potentials decreases under normal circumstances, some of these respond inefficiently to regenerative pressures (eg: brain and heart) while other respond quite well. Therefore creating an optimized micro environment using external means through non-invasive or invasive procedures preferably minimally by utilizing appropriately subjected stem cells/stem cell secretome to induce regeneration at the target sites where it does not take place spontaneously. Stem cell biology is one of the most attractive areas of biomedical research, as emerges for the execution of biotechnology towards the regenerative medicine continues to expand. The presumed potential of the stem cell populations with clonogenic capabilities are harnessed for the therapeutic applications. Advancements in the research technology and the idea of inducing innate regeneration by stem cell based approaches can generate the potential cure for many degenerative disorders, age related disabilities and accidental tissue damages.


Comparison of injectable doxorubicin & its nanodrug complex chemotherapy for the treatment of 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma in rats.
Combination treatments of chemotherapy and nanoparticle drug delivery have shown significant promise in cancer treatment. The aim of the present study was to compare the efficacy of a nanodrug complex with its free form in the treatment of tongue squamous cell carcinoma induced by 4-nitroquinoline-1-oxide in rats. In this study, 75 male Sprague-Dawley rats were divided into five groups. Oral squamous cell carcinoma (OSCC) was induced by using 4- nitroquinoline-1-oxide (4NQO) as a carcinogen. Newly formulated doxorubicin (DOX)-methotrexate (MTX)-loaded nanoparticles, and free DOX-MTX were administrated intravenously to rats. During the study, the animals were weighed once a week. At the end of the treatment, rats' tongues were evaluated histopathologically. There was significant difference between the mean weight of rats in groups A and B (P=0.001) and also groups A and K (P<0.001). No significant association was found between the mortality rate of groups. The difference between the severity of dysplasia of treated and untreated groups was significant (P<0.001). Our study showed that DOX-MTX nanoparticle complex was more effective than free DOX-MTX in chemotherapy treatment of oral squamous cell carcinoma in rat models. Further investigations are necessary to clarify the advantages and disadvantages of the nanoparticle complex and its potential therapeutic application for different types of cancer.


Effectiveness and side effects of UVB-phototherapy, dithranol inpatient therapy and a care instruction programme of short contact dithranol in moderate to severe psoriasis.
The efficacy of UVB-phototherapy (UVB) and dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient dithranol treatment. We found UVB and dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of dithranol is hampered by skin irritation and staining, the present study shows that dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.


Diagnosing Chlamydia Trachomatis Urinary Tract Infections--Preliminary Report.
Chlamydia trachomatis is mentioned among the etiologic factors for urinary tract infections. Chlamydias are parasites inside a cell. A very significant problem of C. trachomatis infections is their asymptomatic character. The most frequent infections caused by these bacteria are inflammations of the urethra and bladder; of the vagina, cervix, vaginal cavity and adnexa in women; and of the epididymis, testicles and prostate in men. In the diagnosis of C. trachomatis infections, the following methods are used: immunofluorescent techniques, immunoenzymatic assays, serological examinations and genetic techniques (for example PCR). The aim of the study was to detect C. trachomatis among patients with symptoms of non-gonorrheal urethritis using diagnostic serologic methods and direct immunofluorescence. The purpose was to assess the connection between the incidence of urinary tract infections caused by C. trachomatis and symptoms that patients report as well as other data from interviews. Blood serum and urethral smears were taken from each of 57 patients. The ELISA method was used to mark specific IgG and IgGcHSP60 anti-chlamydia antibodies in the blood serum. In the urethral smear, antigens were marked using the direct immunofluorescence method. Evidence for urinary tract infection caused by C. trachomatis was found in 15.79% of the examined patients using the immunofluorescence method. In the blood serum, positive results for IgGcHSP60 were obtained in 17.54% of the patients and for IgG in 8.77%. The studies carried out so far suggest that C. trachomatis has a significant role in the etiology of urethritis in adults and children. Other serological tests should be conducted in all the patients in order to study the immune responses in infected individuals and to confirm C. trachomatis infection using genetic methods such as PCR.


THE RELEVANCE OF CYTOLOGICAL DIAGNOSTIC IN THE MAMMARY GLAND CANCER.
Breast cancer is the second leading cause of cancer death in women, while in Eastern Europe the most common form of diagnosed cancer. Out of the multiple possibilities of early detection of mammary neoplasia that have been elaborated, only mammography has proved to be a simple, efficient method and of a high sensitivity, almost 90% However, the cytological confirmation of diagnosis allows us to perform the preoperative radiotherapy treatment or poly chemotherapy. we analyzed the informative value of these diagnosis methods in stage I mammary gland cancer (MGC). In this way, in the present paper we demonstrated that collecting samples through fine-needle aspiration biopsy allows the cytological confirmation of the diagnosis of stage I MGC in 30.7% cases. In stage I MGC young patients, under 35 years, the cytological confirmation rate is 22.2% and is lower as compared to the cytological confirmation rate in patients older than 35 years which is 37.9% Also, for a tumor diameter < 0.5 cm, the prevalence of cytological confirmation was only 10.3%, while for the diameter of 0.6-1.0 cm the cytological confirmation was around 40.0%. Therefore, in order to improve the cytological diagnosis confirmation rate the tumor biopsy through the USG of the mammary glands is required. Moreover, the cytological investigation of the smear obtained by the first and second puncture was instrumental in confirming the diagnosis in 41.3% and 17.4% cases; the subsequent repetition of the punctures was not useful as it helped to confirmation of the diagnosis only in 9.3% cases. The frequency of diagnosis cytological confirmation depends on the tumor histopathological form and type of growth. Thus, the lowest prevalence was in the mixed forms--12.5% cases, lobular cancer--24.4% cases, while regarding the type of growth, for the rare forms the cytological confirmation rate was 7.7% and 31.5% cases for the schiros growth type.


Arginine methylation in a beta-hairpin peptide: implications for Arg-pi interactions, DeltaCp(o), and the cold denatured state.
Arginine methylation is a common post-translational modification that plays a role in many cellular processes through mediation of protein-protein interactions. There is still a dearth of structural information as to its role in mediating such interactions, but the available data suggest a possible role of cation-pi interactions in the recognition of methylated arginine. Hence, the effect of arginine methylation on its interaction with tryptophan has been investigated within the context of a beta-hairpin peptide. Arginine methylation was found to enhance the stacking interaction between the cationic guanidinium functionality of arginine and the indole ring of tryptophan, resulting in structural stabilization of the hairpin. Thermodynamic analysis reveals more favorable entropy of hairpin folding with arginine methylation, a more negative change in heat capacity for folding, and a modest decrease in enthalpic driving force. This is consistent with enhanced stacking and hydrophobic interactions through increased surface area of the guanidinium moiety and greater delocalization of positive charge. In addition, these peptides exhibit significant cold denaturation, which can be accounted for by the inclusion of an expression of temperature-dependent DeltaC(p) in the thermodynamic analysis.


Fate of Escherichia coli O157:H7 in coleslaw during storage.
An outbreak of Escherichia coli O157:H7 infection associated with the consumption of coleslaw in several units of a restaurant chain prompted a study to determine the fate of the pathogen in two commercial coleslaw preparations (pH 4.3 and 4.5) held at 4, 11, and 21 degrees C for 3 days. At an initial population of 5.3 log10 CFU/g of coleslaw, E. coli O157:H7 did not grow in either coleslaw stored at the three temperatures. Rather, the population of E. coli O157:H7 decreased by 0.1 to 0.5 log10 CFU/g within 3 days. The greatest reduction (0.4 and 0.5 log10 CFU/g) in population occurred at 21 degrees C, whereas only slight decreases (0.1 to 0.2 log10 CFU/g) occurred at 4 and 11 degrees C. A pH of 4.3 to 4.5 of coleslaw had little effect on reducing E. coli O157:H7 populations. Results suggest that the tolerance of E. coli O157:H7 to acid pH, not temperature abuse, is a major factor influencing the pathogen's fate in restaurant-prepared coleslaw.


Physiological protection of probiotic microcapsules by coatings.
Nowadays, food and nutrition have a greater impact in people's concerns, with the awareness that nutrition have a direct impact in health and wellbeing. Probiotics have an important role in this topic and consumers are starting to really understand their potential in health, leading to an increasing interest of the companies to their commercial use in foods. However, there are several limitations to the use of probiotics in foods and beverages, being one of them their efficiency (directly associated to their survival rate) upon ingestion. This work is focused in microencapsulation techniques that have been used to increase probiotics efficiency. More specifically, this work reviews the most recent and relevant research about the production and coating techniques of probiotic-loaded microcapsules, providing an insight in the effect of these coatings in probiotics survival during the gastrointestinal phase. This review shows that coatings with the better performances in probiotics protection, against the harsh conditions of digestion, are chitosan, alginate, poly-L-lysine, and whey protein. Chitosan presented an interesting performance in probiotics protection being able to maintain the initial concentration of viable probiotics during a digestive test. The analyses of different works also showed that the utilization of several coatings does not guarantee a better protection in comparison with monocoated microcapsules.


[Sevoflurane anesthesia for pancreatectomy in an infant with nesidioblastosis].
We report a case of nesidioblastosis, which is characterized by hyperinsulinism due to a diffuse increase in the number of beta-cells in the pancreas and, consequently, severe hypoglycemia. The patient was a 79-day-old boy. He had been suffering from severe hypoglycemia despite aggressive treatment, including glucose loading and administration of glucocorticoid and diazoxide. Pancreatectomy was performed. Anesthesia was induced by thiamilal 25 mg and vecronium and was maintained by 1 to 2% sevoflurane in 65% nitrous oxide and fentanyl 5 micrograms. No hemodynamic instability was observed during anesthesia. Blood glucose level was maintained around 200 mg.dl-1 without any hyperglycemic event by continuous infusion of 20% glucose at the rate of 14.5 mg.kg-1.min-1, which was calculated from the daily glucose demand to prevent hypoglycemia preoperatively.


[Beneficial effect of continuous positive airway pressure therapy in obstructive sleep apnea syndrome].
Continuous positive airway pressure therapy is an evidence based therapy of obstructive sleep apnea syndrome. The effective treatment of obstructive sleep apnea can decrease sympaticotonia and, consequently, blood pressure. Furthermore, it can improve inflammatory and metabolic parameters resulting in a decreased cardiovascular risk. This article summarizes the positive effects of continuous positive airway pressure therapy on cardiovascular risk factors in obstructive sleep apnea syndrome.


Pharmaceutical development for treating pancreatic diseases.
The efficacy of medications to treat pancreatic diseases, even when proven effective by experimental studies, are difficult to prove by controlled clinical trials. In the treatment of acute pancreatitis, prophylactic antibiotics, somatostatin, protease inhibitors, and cholecystokinin (CCK)-receptor antagonists are advocated for use in the early stages of acute pancreatitis, but the data are insufficient to mandate prophylaxis use or recommend their use as a standard of care. In the treatment of chronic pancreatitis, digestive enzymes, oral active protease inhibitors, CCK-receptor antagonists, or somatostatin are administered for pain relief. Extracorporeal shock-wave lithotripsy and oral dissolution therapy with trimethadione are used to treat pancreatic stones. The goals of treatment of acute pancreatitis should be to ameliorate the severity of pancreatic inflammation or to prevent its complications. Although several treatments seem to be promising from the studies reviewed, these medications require prospective comparison with the standard procedures and long-term evaluation.


Paralogous translation factors target distinct mRNAs to differentially regulate tolerance to oxidative stress in yeast.
Translation initiation factor 4G (eIF4G) is an integral component of the eIF4F complex which is key to translation initiation for most eukaryotic mRNAs. Many eIF4G isoforms have been described in diverse eukaryotic organisms but we currently have a poor understanding of their functional roles and whether they regulate translation in an mRNA specific manner. The yeast Saccharomyces cerevisiae expresses two eIF4G isoforms, eIF4G1 and eIF4G2, that have previously been considered as functionally redundant with any phenotypic differences arising due to alteration in eIF4G expression levels. Using homogenic strains that express eIF4G1 or eIF4G2 as the sole eIF4G isoforms at comparable expression levels to total eIF4G, we show that eIF4G1 is specifically required to mediate the translational response to oxidative stress. eIF4G1 binds the mRNA cap and remains associated with actively translating ribosomes during oxidative stress conditions and we use quantitative proteomics to show that eIF4G1 promotes oxidative stress-specific proteome changes. eIF4G1, but not eIF4G2, binds the Slf1 LARP protein which appears to mediate the eIF4G1-dependent translational response to oxidative stress. We show similar isoform specific roles for eIF4G in human cells suggesting convergent evolution of multiple eIF4G isoforms offers significant advantages especially where translation must continue under stress conditions.


Is there a relation between computed tomography findings and electrocardiography findings in COVID-19?
COVID-19 can cause lung damage and may present with pneumonia in patients. In the present study, the correlation between the severity of pneumonia and electrocardiography parameters of COVID-19 were examined. A total of 93 COVID-19 patients and a control group consisting of 62 volunteers were studied. Computed thorax tomography evaluation was performed; each lung was divided into three zones. For each affected zone, scores were given. The main computed thorax tomography patterns were described in line with the terms defined by the Fleischner Society and peer reviewed literature on viral pneumonia. We compared Computed thorax tomography of patients with corrected QT (QTc) and P wave dispersion (Pd) time. There is a significant difference between the patient and control groups in terms of QTc values (413.5±28.8 msec vs. 395.6±16.7 msec p<0.001). Likewise, the Pd value of the patient group is statistically significantly higher than that of the control group (50.0±9.6 ms computed thorax tomography ec vs. 41.3±5.8 msec p<0.001). In the patient group, a reverse correlation was detected between computed thorax tomography score and Pd value according to partial correlation coefficient analysis (correlation coefficient: -0.232, p=0.027). In the patient group, the correlation between computed thorax tomography score and QTc value was similarly determined according to partial correlation coefficient analysis (Correlation coefficient:0.224, p=0.017). COVID-19 prolongs QTc and P wave dispersion values; and as the severity of pneumonia increases, QTc value increases. However, whereas the severity of pneumonia increases, P wave dispersion value decreases.


Management of behavioral symptoms in progressive degenerative dementias.
Management of behavioral symptoms of Alzheimer's disease and other progressive degenerative dementias poses continuous challenge to both family and professional caregivers. Behavioral symptoms are complex in nature and require that caregivers understand their presumed causes and intervene appropriately using validated caregiving techniques. Unfortunately, confusing terminology hampers improvement in management techniques. This review attempts to clarify terminology and specifically the behavioral symptoms "agitation" and "resistiveness to care" that require different management techniques. Several conceptual frameworks for behavioral symptoms of dementia are presented. These frameworks include behavioral models, a psychiatric model, and a comprehensive model that combines both behavioral and psychiatric strategies. Using precise terminology consistently and providing care based on a conceptual framework will facilitate the education of caregivers in appropriate techniques for management of behavioral symptoms of dementias.


Pesticide Exposure and Risk of Rheumatoid Arthritis among Licensed Male Pesticide Applicators in the Agricultural Health Study.
The occupation of farming has been associated with rheumatoid arthritis (RA); pesticides may account for this association, but there are few studies. We investigated associations between RA and use of pesticides in the Agricultural Health Study. The study sample was drawn from male pesticide applicators enrolled in 1993–1997 who provided questionnaire data at baseline and at least once during follow-up (over a median 18 y; interquartile range 16–19). Incident RA cases (n=220), confirmed by physicians or by self-reported use of disease-modifying antirheumatic drugs, were compared with noncases (n=26,134) who did not report RA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for enrollment age, state, smoking pack-years, and education. We evaluated the association of RA with the use of 46 pesticides and across 4 levels (never use and tertiles) of lifetime days of use for 16 pesticides with OR≥1.2 for ever use. Incident RA was associated with ever use of fonofos (OR = 1.70; 95% CI: 1.22, 2.37), carbaryl (OR = 1.51; 95% CI: 1.03, 2.23), and chlorimuron ethyl (OR = 1.45; 95% CI: 1.01, 2.07) compared with never use. Statistically significant exposure–response trends in association with RA were observed for lifetime days of use of atrazine [ORtertile3= 1.62 (95% CI: 1.09, 2.40); ptrend=0.01] and toxaphene [ORtertile3= 2.42 (95% CI: 1.03, 5.68); ptrend=0.02]. Exposure–response was nonlinear for fonofos [ORtertile1= 2.27 (95% CI: 1.44, 3.57); ORtertile2= 0.98 (95% CI: 0.54, 1.80); ORtertile3= 2.10 (95% CI: 1.32, 3.36); ptrend=0.005] and suggestive for carbaryl (ptrend=0.053). Our results provide novel evidence of associations between exposure to some pesticides and RA in male farmers. https://doi.org/10.1289/EHP1013.


Gas-containing liver abscesses: assessment by ultrasound (US) and computed tomography (CT).
Single gas-containing pyogenic liver abscesses in 11 patients were studied by ultrasound and computed tomography (CT). On ultrasound, all abscesses were predominantly echogenic compared to the normal liver parenchyma. The gas collections appeared as hyperreflective areas arranged in clusters associated with acoustic shadowing and ring-down artifacts. Ten abscesses (90%) had ill-defined margins on ultrasound, causing underestimation of their sizes in these patients. All abscesses were shown to be multiloculated and had clearly defined borders on CT, not appreciated or mistaken for multiplicity of abscesses on ultrasound. Ultrasound may be inadequate in the evaluation of gas-containing liver abscesses, as they have complex echotexture in addition to ring-down artifacts, acoustic shadows and poorly-defined margins; leading to underestimation of abscess size, difficulty in identifying loculations and erroneous interpretation of multiplicity of abscess cavities.


Advances in understanding the impact of stressful life events on health.
Throughout history, philosophers have debated the interaction of mind and body, but only in the last decade have psychiatrists and other health professionals begun to scrutinize how stressful life events may precipitate or contribute to the onset of illness. While traumatic experiences can profoundly affect physical and psychological well-being, their impact may be mediated by factors such as body chemistry and personality traits, which may predispose an individual to greater resilience or greater vulnerability to life stresses. This review covers research exploring the relationship between life stresses and illness, particularly the eating disorders and myocardial infarction, and describes efforts to develop objective instruments to assess the degree of stress associated with specific life events, a task known as life-events scaling. Avenues for future research are recommended.


Excess Body Mass and Leisure Time Physical Activity in the Incidence and Persistence of Chronic Pain.
To estimate the effects of excess body mass and leisure time physical activity on the incidence and persistence of chronic pain. A prospective cohort study. As a part of the Finnish Helsinki Health Study, we included three cohorts of employees of the City of Helsinki (18,562 observations) and defined incident chronic pain as having pain in any part of the body for more than three months at follow-up in participants without chronic pain at baseline (N = 13,029 observations). Persistent chronic pain was defined as having pain for more than three months at both baseline and follow-up (N = 5,533 observations). Overweight (adjusted odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.06-1.31) and obesity (OR = 1.65, 95% CI = 1.45-1.88) increased the incidence of chronic pain. Moreover, overweight (OR = 1.16, 95% CI = 1.02-1.32) and obesity (OR = 1.48, 95% CI = 1.26-1.74) increased the risk of persistent chronic pain. Vigorous leisure time physical activity reduced the incidence of chronic pain (OR = 0.85, 95% CI = 0.75-0.96). Physical activity did not influence the risk of persistent chronic pain. Furthermore, overweight/obesity modified the effect of leisure time physical activity on incident chronic pain. Inactive overweight or obese participants were at the highest risk of chronic pain (OR = 1.71, 95% CI = 1.40-2.09), while the OR dropped to 1.44 (95% CI = 1.19-1.75) in moderately active overweight or obese participants and to 1.20 (95% CI = 0.97-1.47) in highly active overweight or obese participants. Obesity not only increases the risk of developing chronic pain, but also increases the risk of persistent pain, while leisure time physical activity reduces the risk of developing chronic pain.


Trajectories of internalizing symptoms across childhood: The roles of biological self-regulation and maternal psychopathology.
Whether internalizing symptoms increase or remain at similar levels throughout childhood is currently not well understood. Moreover, the association between vagal regulation of cardiac activity and internalizing symptoms across childhood needs to be clarified. We used a multilevel conceptual framework to examine how children's vagal regulation of cardiac activity and mothers' internalizing symptoms were jointly associated with children's developmental trajectories of internalizing symptoms from ages 4 to 10 years old. Data came from 384 children who participated in an ongoing longitudinal study. Children and their mothers came to the research laboratory at ages 4, 5, 7, and 10. Mothers reported their children's and their own internalizing symptoms. Children's vagal regulation of cardiac activity was assessed during quiet baseline tasks and during challenge tasks. Multilevel models revealed that child internalizing symptoms increased from ages 4 to 10 years old, but only in females, and especially between ages 7 and 10. More vagal withdrawal in response to challenge was associated with more internalizing symptoms, particularly with more somatic symptoms. Associations between children's physiological regulation and internalizing symptoms differed by children's age, sex, and presence of maternal internalizing symptoms. Understanding associations between vagal regulation of cardiac activity and internalizing symptoms during childhood calls for fine-grained developmental analyses that take into account the heterogeneity of internalizing symptoms, as well as developmental phase, context, and gender.


Biomechanics of the classic metaphyseal lesion: finite element analysis.
The classic metaphyseal lesion (CML) is strongly associated with infant abuse, but the biomechanics responsible for this injury have not been rigorously studied. Radiologic and CT-pathological correlates show that the distal tibial CML always involves the cortex near the subperiosteal bone collar, with variable extension of the fracture into the medullary cavity. Therefore, it is reasonable to assume that the primary site of bone failure is cortical, rather than intramedullary. This study focuses on the strain patterns generated from finite element modeling to identify loading scenarios and regions of the cortex that are susceptible to bone failure. A geometric model was constructed from a normal 3-month-old infant's distal tibia and fibula. The model's boundary conditions were set to mimic forceful manipulation of the ankle with eight load modalities (tension, compression, internal rotation, external rotation, dorsiflexion, plantar flexion, valgus bending and varus bending). For all modalities except internal and external rotation, simulations showed increased cortical strains near the subperiosteal bone collar. Tension generated the largest magnitude of cortical strain (24%) that was uniformly distributed near the subperiosteal bone collar. Compression generated the same distribution of strain but to a lesser magnitude overall (15%). Dorsiflexion and plantar flexion generated high (22%) and moderate (14%) localized cortical strains, respectively, near the subperiosteal bone collar. Lower cortical strains resulted from valgus bending, varus bending, internal rotation and external rotation (8-10%). The highest valgus and varus bending cortical strains occurred medially. These simulations suggest that the likelihood of the initial cortical bone failure of the CML is higher along the margin of the subperiosteal bone collar when the ankle is under tension, compression, valgus bending, varus bending, dorsiflexion and plantar flexion, but not under internal and external rotation. Focal cortical strains along the medial margins of the subperiosteal bone collar with varus and valgus bending may explain the known tendency for focal distal tibial CMLs to occur medially. Further research is needed to determine the threshold of applied forces required to produce this strong indicator of infant abuse.


Therapeutic Candidates for Alzheimer's Disease: Saponins.
Drug development for Alzheimer's disease, the leading cause of dementia, has been a long-standing challenge. Saponins, which are steroid or triterpenoid glycosides with various pharmacological activities, have displayed therapeutic potential in treating Alzheimer's disease. In a comprehensive review of the literature from May 2007 to May 2023, we identified 63 references involving 40 different types of saponins that have been studied for their effects on Alzheimer's disease. These studies suggest that saponins have the potential to ameliorate Alzheimer's disease by reducing amyloid beta peptide deposition, inhibiting tau phosphorylation, modulating oxidative stress, reducing inflammation, and antiapoptosis. Most intriguingly, ginsenoside Rg1 and pseudoginsenoside-F11 possess these important pharmacological properties and show the best promise for the treatment of Alzheimer's disease. This review provides a summary and classification of common saponins that have been studied for their therapeutic potential in Alzheimer's disease, showcasing their underlying mechanisms. This highlights the promising potential of saponins for the treatment of Alzheimer's disease.


A Machine Learning-based Method for Question Type Classification in Biomedical Question Answering.
Biomedical question type classification is one of the important components of an automatic biomedical question answering system. The performance of the latter depends directly on the performance of its biomedical question type classification system, which consists of assigning a category to each question in order to determine the appropriate answer extraction algorithm. This study aims to automatically classify biomedical questions into one of the four categories: (1) yes/no, (2) factoid, (3) list, and (4) summary. In this paper, we propose a biomedical question type classification method based on machine learning approaches to automatically assign a category to a biomedical question. First, we extract features from biomedical questions using the proposed handcrafted lexico-syntactic patterns. Then, we feed these features for machine-learning algorithms. Finally, the class label is predicted using the trained classifiers. Experimental evaluations performed on large standard annotated datasets of biomedical questions, provided by the BioASQ challenge, demonstrated that our method exhibits significant improved performance when compared to four baseline systems. The proposed method achieves a roughly 10-point increase over the best baseline in terms of accuracy. Moreover, the obtained results show that using handcrafted lexico-syntactic patterns as features' provider of support vector machine (SVM) lead to the highest accuracy of 89.40 %. The proposed method can automatically classify BioASQ questions into one of the four categories: yes/no, factoid, list, and summary. Furthermore, the results demonstrated that our method produced the best classification performance compared to four baseline systems.


The Psychometric Evaluation of a Speech Production Test Battery for Children: The Reliability and Validity of the Computer Articulation Instrument.
Purpose The aims of this study were to assess the reliability and validity of the Computer Articulation Instrument (CAI), a speech production test battery assessing phonological and speech motor skills in 4 tasks: (1) picture naming, (2) nonword imitation, (3) word and nonword repetition, and (4) maximum repetition rate (MRR). Method Normative data were collected in 1,524 typically developing Dutch-speaking children (aged between 2;0 and 7;0 [years;months]). Parameters were extracted on segmental and syllabic accuracy (Tasks 1 and 2), consistency (Task 3), and syllables per second (Task 4). Interrater reliability and test-retest reliability were analyzed using subgroups of the normative sample and studied by estimating intraclass correlation coefficients (ICCs). Construct validity was investigated by determining age-related changes of test results and factor analyses of the extracted speech measures. Results ICCs for interrater reliability ranged from sufficient to good, except for percentage of vowels correct of picture naming and nonword imitation and for the MRRs for bisyllabic and trisyllabic items. The ICCs for test-retest reliability were sufficient (picture naming, nonword imitation) to insufficient (word and nonword repetition, MRR) due to larger-than-expected normal development and learning effects. Continuous norms showed developmental patterns for all CAI parameters. The factor analyses revealed 5 meaningful factors: all picture-naming parameters, the segmental parameters of nonword imitation, the syllabic structure parameters of nonword imitation, (non)word repetition consistency, and all MRR parameters. Conclusion Its overall sufficient to good psychometric properties indicate that the CAI is a reliable and valid instrument for the assessment of typical and delayed speech development in Dutch children in the ages of 2-7 years.


Role overlap between clinical nurse specialists and nursing unit managers.
Role ambiguity is a serious and costly phenomenon that the healthcare delivery system can ill afford. Classically, it results from a lack of clarity or information concerning the expectations of a role, and it often results in several staff members undertaking the same activities. The resultant inefficiencies are costly to the organization because job satisfaction decreases and the number and quality of applicants for positions decline because people are unsure about the role and its functions. The authors describe an example of role ambiguity that resulted when the new classifications of nursing unit manager and clinical nurse specialist were introduced in New South Wales, Australia, in 1986.


Synthesis and Properties of Polyamide 6 Random Copolymers Containing an Aromatic Imide Structure.
In order to adjust the properties of polyamide 6 (PA6) and expand its application, a new strategy of introducing an aromatic imide structure into the PA6 chain through the random copolymerization method is reported. The diimide diacid monomer was first synthesized by the dehydration and cyclization of pyromellitic dianhydride and 6-aminocaproic acid before it reacted with 1,6-hexamethylene diamine to form poly(amide imide) (PAI) salt, and finally synthesized PA6/PAI random copolymers containing an aromatic imide structure by the random copolymerization of ε-caprolactam and PAI salt. The introduction of an aromatic imide structural unit into the PA6 chain could have a great influence on its properties. As the content of PAI increases, the crystallinity (Xc) and melting temperature (Tm) of the PA6/PAI random copolymer gradually decrease, but its glass transition temperature (Tg) increases obviously. When the PAI content is 20 wt%, the copolymer PA6/PAI-20 has the best comprehensive performance and not only has high thermal stabilities but also excellent mechanical properties (high strength, high modulus, and good toughness) and dielectric properties (low dielectric constant and dielectric loss). Moreover, these properties are significantly superior to those of PA6. Such high-performance PA6 random copolymers can provide great promise for the wider applications of PA6 materials.


[The wax and wane of the trend of "man benefits man" in the late Ming Dynasty].
It was in the period of from Jia Jing to Wan Li Reign that the trend of medication of "man benefits man" appeared with rather great influence in the society. This medication trend experienced a process of rising, zenith, declining, and eventual termination. Among this trend, the refining process of Hong Qian (Red Lead) and Pan Tao Jiu (Mythical Peach Alcohol) was imbued with the ruin of women, arousing debate soon after the trend appeared, with a tit for tat struggle between two medical schools. This research reveals that such medication trend is an adverse current started by fallacious alchemists. Its influence goes beyond the scope of medical field, though its position in the medical province itself is rather low.


Fit of CAD/CAM implant frameworks: a comprehensive review.
Computer-aided design and computer-aided manufacturing (CAD/CAM) is a strongly emerging prosthesis fabrication method for implant dentistry. Currently, CAD/CAM allows the construction of implant frameworks from different materials. This review evaluates the literature pertaining to the precision fit of fixed implant frameworks fabricated by CAD/CAM. Following a comprehensive electronic search through PubMed (MEDLINE), 14 relevant articles were identified. The results indicate that the precision fit of CAD/CAM frameworks exceeded the fit of the 1-piece cast frameworks and laser-welded frameworks. A similar fit was observed for CAD/CAM frameworks and bonding of the framework body to prefabricated cylinders. The influence of CAD/CAM materials on the fit of a framework is minimal.


Effect of short-term exposure of selected aromatic nitrogen compounds on wastewater treatment.
The biodegradation of melamine and p-nitrophenol (PNP) and their impact on wastewater treatment was evaluated after a short-term individual chemical loading in activated sludge treatment systems. Melamine was not degraded and quickly washed out of the system. PNP was degraded, but it led to a prolonged period of nitrification inhibition and deterioration of effluent quality. Both melamine and PNP loadings increased the effluent nitrogen concentrations, with their main contributors being melamine and NH4+, respectively. Nitrosomonas and Nitrospira were dominant in the activated sludge. Melamine did not affect the nitrifying assemblages, whereas PNP led to a reduced Nitrosomonas population size and complete washout of Nitrobacter. The results suggest that melamine is an inert compound if it enters the treatment facility for a short duration. Although the short-term exposure of melamine or PNP decreased effluent water quality,the impact of such aromatic nitrogen compounds on wastewater treatment performance may vary significantly. Water


The metabolic syndrome among postmenopausal women in Ecuador.
The prevalence of the metabolic syndrome increases with age and after the onset of menopause, and may explain in part the apparent acceleration of cardiovascular disease in postmenopausal women. To determine the prevalence of metabolic syndrome and related risk determinants among postmenopausal women in Ecuador. Postmenopausal women >or=40 years of age, non-users of hormone therapy and with an intact uterus, were asked to participate in a metabolic syndrome screening and educational program at the Institute of Biomedicine of the Universidad Católica of Guayaquil, Ecuador. Sociodemographic data, waist circumference and blood pressure measurements were recorded, and a fasting blood sample obtained for serum glucose and lipid profile determinations. Woman were counseled and managed according to the results. Metabolic syndrome was defined in accordance with the criteria of the Third Adult Treatment Panel (ATP III). Three hundred and twenty-five postmenopausal women entered the program. Mean (+/-standard deviation) age was 55.9 +/- 8.1 years, 53.5% of them were aged >or=54 years (median). The prevalence of metabolic syndrome, according to ATP III criteria, was 41.5%. Using the same criteria, 38.8%, 16.6%, 56.9% and 54.2% of the women presented with hypertension, diabetes, hypertriglyceridemia and abdominal obesity, respectively. More than 40% of women determined to have hypertension or diabetes lacked knowing so. Logistic regression analysis determined that age increased the risk of presenting hypertension and diabetes (odds ratio (95% confidence interval): 2.0 (1.2-3.2) and 1.6 (0.9-3.0), respectively, p < 0.05), entities which in turn duplicated the risk of having high triglyceride levels. Sedentary women with <5 years since menopause onset were at higher risk of having abdominal obesity, which was directly related to diabetes and hypertension. In this postmenopausal Ecuadorian population the prevalence of the metabolic syndrome was high and its determinant factors related to age, time since menopause onset and sedentary habits. Because of the implications for cardiovascular risk, counseling programs directed toward high-risk populations should be encouraged.


Risk perception and surveillance uptake in individuals at increased risk for pancreatic ductal adenocarcinoma.
Surveillance for pancreatic ductal adenocarcinoma (PDAC) is recommended for high-risk individuals with genetic variants in PDAC-associated genes and/or family history. Surveillance uptake and adherence may depend on the perception of PDAC risk and cancer worry. We aimed to determine PDAC risk perception in at-risk individuals and assess factors associated with PDAC surveillance uptake. At-risk individuals identified from a prospective academic registry were sent a survey electronically. PDAC risk perception, cancer worry and surveillance uptake were surveyed. Factors associated with increased risk perception and surveillance were assessed. Five-year PDAC risk was calculated using the PancPRO risk assessment model, and correlation with subjective risk assessment was assessed. The overall survey response rate was 34% (279/816). The median perceived PDAC risk was twofold (IQR 1-4) above respondents' estimates of general population risk. Factors significantly associated with higher perceived PDAC risk included non-Hispanic white race, post-graduate education level, PDAC-affected first-degree relative, genetic variants and lack of personal cancer history. Cancer worry had a very weak correlation across PDAC risk estimates (r=0.16). No correlation between perceived PDAC risk and 5-year calculated PDAC risk was found. Older age, having a first-degree relative with PDAC, meeting with a medical provider about PDAC cancer risk and awareness of surveillance modalities were significant predictors of undergoing PDAC surveillance. Individuals at risk for PDAC do not report risk perception that correlates with calculated risk. This presents an opportunity for counselling of at-risk patients to individualise management and improve surveillance uptake for eligible individuals.


Capella's gastroplasty: metabolites and acute phase proteins changes in midline and bilateral arciform approaches.
Obesity has adverse health effects. Dietary reeducation does not seem to offer sustained weight loss. For appropriately selected patients, surgery may be beneficial. To evaluate early postoperative metabolic response to surgery in patients submitted to Capella's gastroplasty using two different surgical approaches to the abdominal cavity. Twenty patients (9 males and 11 females, aged 21 to 53 years) were randomized prior to submission to either one of the surgical access incisions (bilateral arciform or supra-umbilical midline incisions). Blood samples were collected at the beginning and end of the operation, 12 (T-12 h) and 24 hours (T-24 h) postoperatively. Dieresis and synthesis time, blood loss, planimetry of operative field, operative time, hospital stay, hemoglobin, hematocrit, lymphocytes, potassium, albumin, erythrocyte sedimentation rate, C-reactive protein, glucose, pyruvate, lactate and ketone bodies were analyzed. Dieresis time was significantly decreased when median approach was used. Total operating time, hospital stay, hematocrit, hemoglobin, lymphocyte count, potassium and albumin concentrations were similar in both groups. C-reactive protein (T-12 h), glucose and pyruvate concentrations (T-24 h) increased significantly after completion of surgical procedure. Ketone bodies concentrations were significantly decreased 24 hour following completion of surgical procedure. Capella's gastroplasty induces metabolic and inflammatory changes in blood parameters. There is no evidence of technical superiority of arciform over midline incisions in this study.


The timing of cotE expression affects Bacillus subtilis spore coat morphology but not lysozyme resistance.
The synthesis of structural components and morphogenetic factors required for the assembly of the Bacillus subtilis spore coat is governed by a mother cell-specific transcriptional cascade. The first two temporal classes of gene expression, which involve RNA polymerase sigma sigma(E) factor and the ancillary regulators GerR and SpoIIID, are deployed prior to engulfment of the prespore by the mother cell. The two last classes rely on sigma(K), whose activation follows engulfment completion, and GerE. The cotE gene codes for a morphogenetic protein essential for the assembly of the outer coat layer and spore resistance to lysozyme. cotE is expressed first from a sigma(E)-dependent promoter and, in a second stage, from a promoter that additionally requires SpoIIID and that remains active under sigma(K) control. CotE localizes prior to engulfment completion close to the surface of the developing spore, but formation of the outer coat is a late, sigma(K)-controlled event. We have transplanted cotE to progressively later classes of mother cell gene expression. This created an early class of mutants in which cotE is expressed prior to engulfment completion and a late class in which expression of cotE follows the complete engulfment of the prespore. Mutants of the early class assemble a nearly normal outer coat structure, whereas mutants of the late class do not. Hence, the early expression of CotE is essential for outer coat assembly. Surprisingly, however, all mutants were fully resistant to lysozyme. The results suggest that CotE has genetically separable functions in spore resistance to lysozyme and spore outer coat assembly.


The Cost of Activity during the Rest Phase: Animal Models and Theoretical Perspectives.
For humans, activity during the night is correlated with multiple pathologies that may reflect a lack of harmony among components of the circadian system; however, it remains difficult to identify causal links between nocturnal activity and different pathologies based on the data available from epidemiological studies. Animal models that use forced activity or timed sleep deprivation provide evidence of circadian disruptions that may be at the core of the health risks faced by human night and shift workers. One valuable insight from that work is the importance of changes in the distribution of food intake as a cause of metabolic imbalances associated with activity during the natural rest phase. Limitations of those models stem from the use of only nocturnal laboratory rodents and the fact that they do not replicate situations in which humans engage in work with high cognitive demands or engage voluntarily in nocturnal activity (i.e., human eveningness). Temporal niche switches by rodents have been observed in the wild and interpreted as adaptive responses to energetic challenges, but possible negative outcomes, similar to those associated with human eveningness, have not been systematically studied. Species in which a proportion of animals shows a switch from a day-active to a night-active (e.g., grass rats) when given access to running wheels provide a unique opportunity to model human eveningness in a diurnal rodent. In particular, the mosaic of phases of brain oscillators in night-active grass rats may provide clues about the circadian challenges faced by humans who show voluntary nocturnal wakefulness.


Quantitative Elasticity Mapping of Submicron Silica Hollow Particles by PeakForce QNM AFM Mode.
Silica hollow spheres with a diameter of 100-300 nm and a shell thickness of 8±2 nm were synthesized using a self-templating amphiphilic polymeric precursor, i.e., poly(ethylene glycol)-substituted hyperbranched polyethoxysiloxane. Their elastic properties were addressed with a high-frequency AFM indentation method based on the PeakForce QNM (quantitative nanomechanical mapping) mode enabling simultaneous visualization of the surface morphology and high-resolution mapping of the mechanical properties. The factors affecting the accuracy of the mechanical measurements such as a local slope of the particle surface, deformation of the silica hollow particles by a solid substrate, shell thickness variation, and applied force range were analysed. The Young's modulus of the shell material was evaluated as E=26±7 GPa independent of the applied force in the elastic regime of deformations. Beyond the elastic regime, the buckling instability was observed revealing a non-linear force-deformation response with a hysteresis between the loading and unloading force-distance curves and irreversible deformation of the shell at high applied forces. Thus, it was demonstrated that PeakForce QNM mode can be used for quantitative measurements of the elastic properties of submicon-sized silica hollow particles with nano-size shell thickness, as well as for estimation of the buckling behaviour beyond the elastic regime of shell deformations.


Therapeutic targets and nanomaterial-based therapies for mitigation of secondary injury after spinal cord injury.
Spinal cord injury (SCI) and the resulting neurological trauma commonly result in complete or incomplete neurological dysfunction and there are few effective treatments for primary SCI. However, the following secondary SCI, including the changes of microvasculature, inflammatory response and oxidative stress around the injury site, may provide promising therapeutic targets. The advances of nanomaterials hold promise for delivering therapeutics to alleviate secondary SCI and promote functional recovery. In this review, we highlight recent achievements of nanomaterial-based therapy, specifically targeting blood-spinal cord barrier disruption, mitigation of the inflammatory response and lightening of oxidative stress after spinal cord injury.


Biodegradation of polyfluoroalkyl phosphates as a source of perfluorinated acids to the environment.
Wastewater treatment plants (WWTPs) have been identified as a major source of perfluorocarboxylates (PFCAs) to aqueous environments. The observed increase in PFCA mass flows from WWTP influent to effluent suggests the biodegradation of commercial fluorinated materials within the WWTP. Commercial fluorinated surfactants are used as greaseproofing agents in food-contact paper products as well as leveling and wetting agents. As WWTPs are likely the major fate of these surfactants, their biodegradation may be a source of PFCA production. One class of commercial surfactants, the polyfluoroalkyl phosphates (PAPs), have been observed in WWTP sludge. While PAPs have been shown to degrade into PFCAs in a rat model, the present study investigates their microbial fate to determine whether the biodegradation of PAPs within a WWTP-simulated system will contribute to the load of PFCAs released. PAPs are applied commercially in mixed formulations of different chain lengths and substitution at the phosphate center. The effect of chain length and phosphate substitution on the biodegradation of PAPs was investigated by incubating mixtures of 4:2, 6:2, 8:2, and 10:2 monosubstituted PAPs (monoPAPs) in an aerobic microbial system and by separately incubating the 6:2 monoPAP and 6:2 disubstituted PAP (diPAP) for 92 days. Headspace sampling revealed production of the fluorotelomer alcohols (FTOHs) from the hydrolysis of the PAP phosphate ester linkages. Analysis of the aqueous phase revealed microbial transformation of the PAPs to the final PFCA products was possible. The majority of the oxidation products observed were consistent with previous investigations that have suggested fluorotelomer precursor compounds degrade predominantly via a beta-oxidation-like mechanism. However, in this study, the detection of odd-chain PFCAs suggests that other pathways may be important. The present study demonstrated microbially mediated biodegradation of PAPs to PFCAs. This observation, together with the diPAP concentrations observed in WWTP sludge, suggest PAPs-containing commercial products may be a significant contributor to the increased PFCA mass flows observed in WWTP effluents.


The Role of Non-alcoholic Fatty Liver Disease in Cardiovascular Disease.
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in western countries and is closely related to the metabolic syndrome. When NAFLD is associated with hepatocellular damage and inflammation (non-alcoholic steatohepatitis [NASH]) it can lead to severe liver disease. However, it has become clear that NAFLD is also associated with an increased risk of cardiovascular disease (CVD), independently of classical known risk factors for the latter. In the current review we briefly summarise the current clinical evidence on the role of NAFLD in CVD and discuss the potential mechanisms by which NAFLD can be linked to the pathophysiology of CVD.


In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury.
The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET-MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of infiltrating monocytes from an inflammatory (Ly6Chigh ) to a repair (Ly6Clow ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology. Here, using an acute sterile skeletal muscle injury model combined with irradiation, bone marrow transplantation and in vivo imaging, we show that preserved muscle integrity and cell composition prior to the injury is necessary for the repair macrophage phenotypic transition and subsequently for proper and complete tissue regeneration. Importantly, by using a model of in vivo ablation of PAX7 positive cells, we show that this radiosensitive skeletal muscle progenitor pool contributes to macrophage phenotypic transition following acute sterile muscle injury. In addition, local muscle tissue radioprotection by lead shielding during irradiation preserves normal macrophage transition dynamics and subsequently muscle tissue regeneration. Taken together, our data suggest the existence of a more extensive and reciprocal cross-talk between muscle tissue compartments, including satellite cells, and infiltrating myeloid cells upon tissue damage. These interactions shape the macrophage in situ phenotypic shift, which is indispensable for normal muscle tissue repair dynamics.