Determination of 14 trace elements in blood, serum and urine after environmental disaster in the Doce River basin: Relationship between mining waste and metal concentration in the population.
Exposure to chemical substances after an environmental disaster can cause both toxic effects and changes in the health status of people who live in or have proximity to environments of this nature, so that the concern with populations is growing. In this cross-sectional study, blood, serum and urine samples were collected from 100 volunteers from Santo Antônio do Rio Doce, eight from Ilha das Pimentas and 50 from the control group; and analyzed by inductively coupled plasma mass spectrometry for biomonitoring of Al, As, Ba, Cd, Co, Cu, Cr, Fe, Hg, Mn, Ni, Se, Pb, Zn. In addition, a comprehensive questionnaire was applied to collect demographic and socioeconomic information, as well as lifestyle. The concentrations of As, Al, Cd, Ni and Mn were above the reference value in some biological matrices, with more pronounced exposure in Ilha das Pimentas. The concentrations of As, Cd, Cu, Co, Pb and Zn showed statistical differences regarding gender in the different biological matrices. The trace elements in the blood, serum and urine showed significant correlations when considering age and habits such as the consumption of cigarettes, alcoholic beverages and fish. The main correlations were observed between Co, Cr, Mn, Ni and Pb in the blood and cigarette consumption. This is the first study in these regions after the environmental disaster and confirmation of the diagnosis and health care of the participants should be promoted for clinical investigation and the eventual need for treatment. Human biomonitoring demonstrated high concentrations of some toxic elements, with more accentuated exposure in Ilha das Pimentas.


The regulatory pathways of distinct flowering characteristics in Chinese jujube.
Flowering is the most important event in higher plants. Compared to most fruit tree species, Chinese jujube (Ziziphus jujuba Mill.), the most important member of the large, diverse Rhamnaceae family and a leading dry fruit-producing species, has unique characteristics that include a short juvenile phase and extremely fast flower bud differentiation. However, the distinct mechanism of flowering regulation in Chinese jujube is still unclear. The morphological and cytological development period of jujube flowering was first investigated, and the crucial developmental stages were defined. Flower bud differentiation in Chinese jujube took only approximately 11-13 days, which is a distinct characteristic of perennial fruit trees. Afterward, 44 genes related to six flowering pathways were identified in the jujube genome and were found to be randomly distributed among 11 of the 12 chromosomes. Tissue-specific and spatiotemporal expression patterns showed that all these genes were expressed in the flowers. Overall, photoperiod-related genes were highly expressed during flower bud differentiation. These genes were also positively responsive to photoperiod regulation and phase change processes, indicating that photoperiod- related genes play crucial roles in jujube flower bud differentiation. Under protected cultivation, ZjPIF4, a temperature-related gene, was expressed in the early stages of flowering and responded to increasing temperatures. Moreover, STRING analysis and yeast two-hybrid screening indicated that photoperiod-related (ZjCO) and temperature-related (ZjPIF4) proteins could interact with ZjFT, the key protein involved in the determination of flowering time, indicating crosstalk between photoperiod-related pathways and ambient temperature-related pathways in jujube. This study is the first report to comprehensively analyze the flowering pathways in Chinese jujube and revealed that photoperiod-related and ambient temperature-related pathways are the main mechanisms regulating the distinct flowering process and that members of the ZjPHY family (ZjPIF4, ZjFT, and ZjCO5) are the key factors involved in the regulatory network. These results will increase our understanding of the molecular and genetic mechanisms of flowering in Chinese jujube and provide meaningful clues for the flowering regulation of other fruit tree species.


Complement activation fragment Bb in early pregnancy and spontaneous preterm birth.
The objective of this study was to determine whether an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks' gestation or SPTB between 34 and 37 weeks' gestation (late SPTB). This was a prospective study of 784 women enrolled at less than 20 weeks' gestation. Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks' gestation and 25 (3.2%) a SPTB between 34 and 37 weeks' gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks' gestation as compared with women who had levels of Bb in the lower 3 quartiles (95% confidence interval [CI] 1.5-14, P = .003). There was no association between Bb and late SPTB (relative risk 0.8, 95% CI 0.3-2). A significant relationship was found between an elevated Bb in early pregnancy and SPTB less than 34 weeks' gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition.


Simultaneous operation of three catabolic pathways in the metabolism of glucose by Thiobacillus A2.
Enzymes essential to the operation of the Embden-Meyerhof glycolytic pathway, the Entner-Duodoroff pathway and oxidative pentose phosphate pathway were present in Thiobacillus A2 grown on glucose and other sugars. Radiorespirometry under various conditions with Thiobacillus A2 oxidising glucose specifically labelled with 14C in carbon atoms 1, 2, 3, 3 + 4, 6 or universally labelled demonstrated the simultaneous operation of the Embden-Meyerhof (48%), Entner-Doudoroff (28%), and pentose phosphate (24%) pathways in release of carbon dioxide from glucose. Growth on succinate, or autotrophically on formate or thiosulphate resulted in repression of most enzymes of the pathways, but high aldolase levels were retained indicating its role in gluconeogenesis and the Calvin cycle. Different fructose diphosphatase activities were found in succinate- and thiosulphate-grown organisms. The results indicate that all three major catabolic pathways for glucose function in Thiobacillus A2 grown on sugars. Thiobacillus acidophilus showed a different radiorespirometric pattern and apparently used the Entner-Duodoroff (64.5%) and pentose phosphate (35.5%) pathways, but showed unusually high release of carbon atom 6, as was also found for T. ferrooxidans.


Green and enhanced extraction of coumarins from Cortex Fraxini by ultrasound-assisted deep eutectic solvent extraction.
Green and enhanced extraction of bioactive ingredients from medicinal plants has become a hot research field, and deep eutectic solvents have been considered as a novel kind of sustainable solvents in the extraction process. In this study, hydrogen bond acceptor (choline chloride, etc.) and hydrogen bond donor (l-malic acid, etc.) were used to prepare different kinds of deep eutectic solvents to extract coumarins from Cortex Fraxini. The extraction conditions, including the composition and moisture content of deep eutectic solvents, extraction time, and liquid-solid ratio, were systematically optimized basing on the extraction yield of coumarins. To further investigate the extraction mechanism, Fourier transform infrared spectroscopy was performed, and the microstructures of Cortex Fraxini powders were observed before and after extraction using scanning electron microscope. Results showed that the novel ultrasound-assisted extraction with conditions of deep eutectic solvent containing betaine/glycerin (1:3), aqueous solution (20%), solid-liquid ratio (15 mg/mL), and extraction time (30 min) exhibited the best extraction yields for the four target coumarins and much better extraction efficiency than with conventional solvent extractions. This suggests that the new ultrasound-assisted deep eutectic solvent extraction could be used as a green and high-efficient approach for extraction of the main coumarins from Cortex Fraxini.


Pediatric Granulomatosis With Polyangiitis Mimicking IgA Vasculitis: A Case Report.
Granulomatosis with polyangiitis (GPA) is a systemic vasculitis of the upper and lower respiratory tract along with glomerulonephritis and is very rare in childhood. Its renal manifestations similarity with IgA vasculitis can be misleading. Herein, we report a 12-years-old girl with the clinical picture of IgA vasculitis and renal involvement at the time of presentation, over time, elevated cytoplasmic Anti-neutrophil Cytoplasmic Antibody (C-ANCA) and tissue biopsy confirmed GPA. In the case of a patient with an unusual presentation of IgA vasculitis, to some degree of suspicion, the GPA should be considered. Also, in approach to non-thrombocytopenic palpable petechia and purpura a wide range of differential diagnosis such as infections, ANCA associated vasculitis, and secondary vasculitis should be considered. Therefore, 2 effective method of GPA diagnosis, the high titer of C-ANCA test and tissue biopsy, should be considered simultaneously.


Clinical Profile and Outcome of Pediatric Sarcoidosis.
To document clinical features and outcome of children with sarcoidosis. Case records of 18 children (mean (SD) age 9 (2.2) years) diagnosed with sarcoidosis between 2006 and 2016 were reviewed. All children were followed up every 2-3 months and monitored for clinical and laboratory parameters. Their treatment and outcome were recorded. Clinical features at the time of diagnosis were fever (83%), uveitis (50%), difficulty in breathing (44%), hepatosplenomegaly, weight loss, arthritis and peripheral adenopathy. Imaging findings included: hilar adenopathy (94%), abdominal nodes (50%) and pulmonary infiltrates (44%). All children were treated with steroids (range 6-12 months) and weekly low dose oral methotrexate. All patients showed significant improvement over a mean (SD) duration of follow-up of 3.1 (0.9) years, as assessed by resolution of clinical symptoms, and improvement in spirometry parameters, erythrocyte sedimentation rate, and serum angiotensin converting enzyme levels. Children with sarcoidosis seem to respond well to systemic steroids and low dose methotrexate. Delayed diagnosis and ocular involvement are probably associated with poor outcome.


Effects of totally extraperitoneal (TEP) and Lichtenstein hernia repair on testicular blood flow and volume.
Laparoscopic totally extraperitoneal hernia repair (TEP) has been compared with the open technique in several studies in terms of technical properties and perioperative outcomes. There are few studies that compare the long-term effects of each technique on testicular structure and function on the side of the hernia repair. The objective of this study is to investigate the effects at 6 months of the TEP and the Lichtenstein technique on testicular volume and arterial flow by the use of Doppler ultrasonography. A total of 148 men with a unilateral hernia were randomized prospectively to undergo TEP or Lichtenstein repair. In both groups, unilateral resistive indices, pulsatile indices of capsular and intratesticular artery flow, and testicular volume (in milliliters) were measured preoperatively and 6 months postoperatively by the use of grayscale and color Doppler ultrasonography (CDUS). The primary outcomes of the study were postoperative findings from history, physical examination, and CDUS measurements at 6 months postoperatively. Demographics, clinical and operative data, CDUS measurements, and recurrence patterns were analyzed. Of 148 procedures, 134 cases consisting of 64 TEP and 70 Lichtenstein repairs were evaluated. Pre- and postoperative CDUS findings, rates of complications, and recurrence in both groups did not show any difference. Operative time was greater with a Lichtenstein repair (36 vs 30 minutes; P = .01). Complications and recurrence rates and effects on testicular perfusion and testicular volume in both laparoscopic and open techniques are similar, whereas the laparoscopic approach has shorter operative time than open hernia repair.


Clindamycin and lincomycin alter miniature endplate current decay.
Antibiotic-induced muscle paralysis has frequently been found in both experimental animals and man with three distinct classes of antibiotic: (1) streptomycin and related aminoglycoside compounds, (2) polymyxins and (3) tetracyclines. Recently lincomycin and its chemical congener, clindamycin, have been reported to produce muscle paralysis which has different characteristics from those seen with other classes of antibiotic. Although closely related in chemical structure, lincomycin and clindamycin also seem to produce muscle paralysis by different mechanisms. Clindamycin is considered to exert a direct depressant action on muscle contractility whereas the action of lincomycin is considered to be primarily a depression of neuromuscular transmission. We report here that each of these antibiotics had a significant but different influence on endplate channel behaviour. Clindamycin increased the rate of miniature endplate current (m.e.p.c.) decay and reduced its voltage sensitivity without altering its exponential nature. Lincomycin split m.e.p.c. decay into an initial rapid phase followed by a prolonged phase.


Can the presence of cat/dog at home be considered the only criterion of exposure to cat/dog allergens? A likely underestimated bias in clinical practice and in large epidemiological studies.
An important aspect of allergic sensitization to furry animals is the association of dog and cat exposure in early childhood with the incidence of respective allergies later in life. This topic is very controversial, because some authors have found a "facilitating" effect, while others have noticed a "protective" or even no significant effect in individuals living in urban areas. It is likely that some biases could be responsible of these contradictory findings. Cat/dog ownership or their presence in indoor environments are considered usually the main criteria to assess the exposure to these pets in studies' questionnaires. Even in clinical practice "are there animals at home?" is the common query usually done when collecting anamnestic data. In our opinion, these commonly used questions should not be considered the main index of exposure to pet allergens, because they can lead to erroneous interpretation of the clinical significance of positive skin prick tests for pet allergens as well as of the real risk of exposure to allergens of dog/cat in epidemiological studies. Consequently, we suggest a new, more realistic, classification of modalities of exposure to pet allergens in "real life" based on five possible conditions.


Inflammatory markers of complete blood count in Fuchs uveitis syndrome.
To evaluate inflammatory indices of complete blood count (CBC) in patients with Fuchs uveitis syndrome (FUS), and to compare the results with healthy individuals. Cross-sectional, comparative study. A total of 140 participants were included in the study and divided into 2 groups: 70 patients diagnosed with FUS (FUS group) and 70 healthy individuals (control group). The groups were compared in terms of ocular examination findings and CBC parameters. The independent samples t test was used to examine variables between the groups. The Pearson correlation test was performed to analyze correlation among the severity of anterior chamber reaction, duration of FUS, and CBC indices. The mean lymphocyte count and lymphocyte-to-monocyte ratio (LMR) were significantly higher in the FUS group than in the control group (p = 0.001 and p < 0.001, respectively). The mean monocyte count and neutrophil-to-lymphocyte ratio (NLR) were significantly lower in the FUS group than in the control group (p = 0.010 and p = 0.003, respectively). In the receiver operating characteristic curve analysis, the area under the curve (AUC) for LMR was 0.834, with a sensitivity of 82.6% and a specificity of 80.0%. The AUC for NLR was 0.789, with a sensitivity of 71.2% and a specificity of 70.0%. LMR was positively correlated with duration of FUS (p = 0.001, r = 0.574). Our findings suggest that decreased NLR and increased LMR values may be markers indicating impaired blood-aqueous barrier function in FUS.


Conventional versus fibrin-glue-augmented arterial microanastomosis: An experimental study.
The purpose of this experimental study was to develop an alternative technique of arterial microanastomosis using only 2 stay-sutures augmented with fibrin glue, and to compare it to the conventional technique in arteries of varying diameters mimicking hand arteries. Eight anastomoses were performed in 7 male rats, including 1 anastomosis each on the 2 femoral, iliac, and carotid arteries, and 2 on the subrenal aorta. The conventional technique was used on one side and on the first aorta anastomosis, while augmented anastomoses were performed on the other side and on the second aorta. Patency was tested 10 min after unclamping; clamping time, blood loss, anastomosis quality score (out of 15 points) and artery diameter were recorded. In arteries of diameter 0.5-2.2 mm, augmented anastomoses were on average 10.7 ± 3.2 min faster to perform (p < 0.0001), with an average of 1.3 ± 0.9 g less blood loss (p < 0.0001) and an average of 2.6 ± 2.5 points higher quality score (p < 0.0001). There were no significant differences between the two techniques in terms of patency rate, regardless of artery size. However, 3 of the 7 augmented anastomoses were non-permeable in the femoral subgroup (i.e., submillimetric arteries). This straightforward technique appears to be time-saving and reliable, provided that the repaired artery is of sufficient size. Subject to clinical validation, this technique might help surgeons treating extensive hand wounds with multiple severed neurovascular bundles.


Ultrasonic Substrate Vibration-Assisted Drop Casting (SVADC) for the Fabrication of Photovoltaic Solar Cell Arrays and Thin-Film Devices.
A simple, low-cost, versatile, and potentially scalable casting method is proposed for the fabrication of micro- and nano-thin films, herein termed as ultrasonic "substrate vibration-assisted drop casting" (SVADC). The impingement of a solution drop onto a substrate in a simple process called drop casting, usually results in spreading of the liquid solution and the formation of a non-uniform thin solid film after solvent evaporation. Our previous and current supporting results, as well as few similar reports by others, confirm that imposing ultrasonic vibration on the substrate can simply convert the uncontrollable drop casting method into a controllable coating technique. Therefore, the SVADC may be used to fabricate an array of emerging thin-film solar cells, such as polymer, perovskite, and quantum-dot solar cells, as well as other small thin-film devices, in a roll-to-roll and automated fabrication process. The preliminary results demonstrate a ten-fold increase in electrical conductivity of PSS made by SVADC compared with the film made by conventional drop casting. Also, simple planar perovskite solar cells made here using SVADC show promising performance with an efficiency of over 3 % for a simple structure without performing process optimization or using expensive materials and treatments.


Insertional Achilles tendinopathy is associated with arthritic changes of the posterior calcaneal cartilage: a retrospective study.
To characterize the histological changes within the posterior calcaneal cartilage in patients with insertional Achilles tendinopathy (IAT) and test the relationships between severity of the histological changes and level of functional impairment. Sixteen posterior calcaneal wall specimens of patients with IAT who had posterior calcaneal ostectomy were investigated. Hematoxylin-eosin stain, Toluidine-blue stain, Polarized light microscopy, and Masson Trichrome stain were used to characterize histological changes. Changes within the posterior calcaneal wall cartilage were graded according to Osteoarthritis Research Society International (OARSI) criteria. Functional scores were completed at the time of surgery according to the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score. Mean age of patients was 48.9 years. Histological findings within the posterior calcaneal wall cartilage specimens were consistent with arthritic changes. OARSI grading indicated Grade 2 changes in one specimen, mean AOFAS score 60; Grade 3 changes in three specimens, AOFAS score 73.7 ± 2.5; Grade 4 changes in four specimens, AOFAS score 44 ± 21.4; Grade 5 changes in eight specimens, AOFAS score 48 ± 9.9. Higher OARSI grades were correlated with lower AOFAS scores (rho = -0.65, p < 0.01). Degenerative arthritic changes of the posterior calcaneal wall cartilage characterize patients with IAT and the severity of such changes is directly correlated to the degree of functional impairment.


6: Thyroid nodules and thyroid cancer.
Thyroid nodules are common clinically (prevalence, about 5%) and even more common on ultrasound examination (about 25%). About 5% of thyroid nodules are malignant. Most thyroid cancers are well-differentiated papillary or follicular tumours with an excellent prognosis (10-year survival, 80%-95%). The incidence of papillary thyroid cancer appears to be increasing on the east coast of Australia. Fine-needle aspiration biopsy of the thyroid is the most cost-effective diagnostic tool. Recommended initial management of all follicular carcinomas and of papillary carcinomas > 1.0 cm is total thyroidectomy followed by radioiodine ablation. Most patients should be managed postoperatively with doses of thyroid hormone sufficient to suppress plasma levels of thyroid-stimulating hormone. Recurrences can occur many years after initial therapy, and follow-up should be lifelong. Thyroid nodules are very common, but have a relatively low risk of malignancy


Pilot-scale investigation of the robustness and efficiency of a copper-based treated wood wastes recycling process.
The disposal of metal-bearing treated wood wastes is becoming an environmental challenge. An efficient recycling process based on sulfuric acid leaching has been developed to remove metals from copper-based treated wood chips (0<x<12 mm). The present study explored the performance and the robustness of this technology in removing metals from copper-based treated wood wastes at a pilot plant scale (130-L reactor tank). After 3 × 2 h leaching steps followed by 3 × 7 min rinsing steps, up to 97.5% of As, 87.9% of Cr, and 96.1% of Cu were removed from CCA-treated wood wastes with different initial metal loading (>7.3 kgm(-3)) and more than 94.5% of Cu was removed from ACQ-, CA- and MCQ-treated wood. The treatment of effluents by precipitation-coagulation was highly efficient; allowing removals more than 93% for the As, Cr, and Cu contained in the effluent. The economic analysis included operating costs, indirect costs and revenues related to remediated wood sales. The economic analysis concluded that CCA-treated wood wastes remediation can lead to a benefit of 53.7 US$t(-1) or a cost of 35.5 US$t(-1) and that ACQ-, CA- and MCQ-treated wood wastes recycling led to benefits ranging from 9.3 to 21.2 US$t(-1).


Complement activation in septic baboons detected by neoepitope-specific assays for C3b/iC3b/C3c, C5a and the terminal C5b-9 complement complex (TCC).
We have investigated the cross-reactivity of various species in neoepitope-specific methods for quantification of human complement activation products. In contrast to most other species examined, baboon showed a substantial cross-reactivity supporting a high degree of homology between human and baboon complement. An assay for C3b, iC3b and C3c (MoAb bH6) showed moderately good reactivity, in contrast to a C3a assay which did not cross-react. Excellent reactivity was found for C5a using MoAbs C17/5 and G25/2. The reactivity of an established TCC assay (MoAb aE11 to a C9 neoepitope and polyclonal antibody to C5) was improved substantially by replacing the anti-C5 antibody with a new MoAb to C6 particularly selected on the basis of baboon cross-reactivity. Plasma samples from baboons receiving 2.5 x 10(9) and 1.0 x 10(10) live Escherichia coli bacteria/kg were examined with the assays described. In vivo complement activation with the lowest dose was moderate and kept under control, in contrast to the highest dose, where an uncontrolled increase in all activation products continued throughout the infusion period. These results support the hypothesis that sufficiently high amounts of endotoxin lead to uncontrolled activation of complement as seen in irreversible septic shock. The results are discussed with particular emphasis on activation of the terminal complement pathway.


Analytical isotachophoresis in capillary tubes. Analysis of hemoglobin, hemiglobin cyanide and isoelectric fractions of hemiglobin cyanide.
The zone stabilization in capillary isotachophoresis in the water phase has been improved by methylcellulose so that proteins can be analysed. Hemoglobin and hemiglobin cyanide samples were studied as model systems. Ampholine carrier ampholytes were used as spacers, enhancing the detection of the different components. The optimal amounts of Ampholine, however, were found to be much smaller than in most of the previously published reports. Linear relationships were found between the zone lengths and sample amounts, including spacers. The separations were reproducible and reached the isotachophoretic steady state. The hemiglobin cyanide was fractionated by isoelectric focusing. The four main fractions were then analyzed by capillary isotachophoresis and shown to be heterogeneous in mobility with a pH of 7.5 in the leading electrolyte. The component zones of the total hemiglobin cyanide sample were all identified in relation to the isotachophoretic components of the isoelectric fractions. The total analysis time was in average 30-40 min. The sample amounts were about 40 mug protein in each experiment with very small Ampholine volumes, 25-100 nl 40% (w/v).


TRP and Rhodopsin Transport Depends on Dual XPORT ER Chaperones Encoded by an Operon.
TRP channels and G protein-coupled receptors (GPCRs) play critical roles in sensory reception. However, the identities of the chaperones that assist GPCRs in translocating from the endoplasmic reticulum (ER) are limited, and TRP ER chaperones are virtually unknown. The one exception for TRPs is Drosophila XPORT. Here, we show that the xport locus is bicistronic and encodes unrelated transmembrane proteins, which enable the signaling proteins that initiate and culminate phototransduction, rhodopsin 1 (Rh1) and TRP, to traffic to the plasma membrane. XPORT-A and XPORT-B are ER proteins, and loss of either has a profound impact on TRP and Rh1 targeting to the light-sensing compartment of photoreceptor cells. XPORT-B complexed in vivo with the Drosophila homolog of the mammalian HSP70 protein, GRP78/BiP, which, in turn, associated with Rh1. Our work highlights a coordinated network of chaperones required for the biosynthesis of the TRP channel and rhodopsin in Drosophila photoreceptor cells.


The production and verification of pristine semi-fluorinated thiol monolayers on gold.
The presence of adventitious contamination of self-assembled monolayers (SAMs) is a well-known phenomenon that is often overlooked or underestimated in the literature. Herein, we demonstrate that it is possible to produce pristine self-assembled monolayers (SAMs) on gold surfaces that are devoid of adventitious species. The chemical purity or the pristine quality of the SAM was verified by the experimental relative atomic ratios measured by X-ray photoelectron spectroscopy (XPS) of all elements including carbon and corresponded to within 5% of the stoichiometric ratios. Perfluoro-octyl-thiolate (F8) was used as a model compound in this study, where monolayers were assembled from solutions of an acetylated F8 precursor. Quantitative elemental characterization of the acetylated F8 precursor by cold-stage XPS provided valuable reference data for the analysis of the subsequent SAMs. Comprehensive analysis of high-resolution XPS C 1s spectra proved to be essential for establishing the purity of the SAMs, since the peaks of the adventitious species were easily distinguished from those of the F8. Analyses of deliberately contaminated F8 SAMs showed that the adventitious species persisted during the process of self-assembly and therefore co-existed with the SAM in the interfacial region. The work also established that even a lengthy deposition time of 18 h was incapable of displacing the adventitious species present at the interface.


Chain conformations and steady-shear viscosity properties of pectic polysaccharides from apple and tomato.
In this study, apple pectin (AP) and tomato pectin (TP) were demonstrated to be a high-ester (74.8%) polysaccharide with the weight-average molecular weight (Mw ) of ∼ 243 kDa and a low-ester (45.9%) polysaccharide with the Mw of ∼ 19 kDa, respectively. The semi-rigid chain conformations of pectic polysaccharides in NaNO3 aqueous solution were deduced according to the Smidsrød "B values" of AP (0.025) and TP (0.029), while AP and TP exhibited higher stiffness in water due to the electric repulsion of carboxyl groups, which was visually observed by AFM images. Under steady shear, the shear-thickening behaviors of AP and TP in NaNO3 aqueous solutions were observed in the shear rate range of < 1 s-1, which were attributed to the disruption of the ordered arrangement induced by semi-rigid pectin chains into randomly entangled structure by weak shear force. AP exhibited stronger shear-thickening behavior due to the formation of more entanglements resulted from the higher Mw and longer side chains highly branched at rhamngalacturonan region. This study provides the scientific basis for the construction of the relationship of steady-shear property with chain conformation and molecular weight of pectin.


A retrospective analysis of the sentence writing component of the Mini Mental State Examination: cognitive and affective aspects.
One of the components of the Mini Mental State Examination (MMSE) is the request to write a sentence. We investigated the relationship between the characteristics of the written sentence of the MMSE and the cognitive and affective status of elderly patients. The characteristics of the sentence were compared to the total MMSE score, sociodemographic characteristics, tests evaluating cognition and affective status, and diagnoses. The number of words was significantly associated with the degree of cognitive impairment, whereas the emotional polarity of sentences and concerns about health were associated with depression. Characteristics of the MMSE sentence may provide important additional information regarding both cognition and affect when assessing older people.


Development and validation of the infant feeding intentions scale.
There is a need in breastfeeding behavior studies for a quantitative measure of maternal breastfeeding intentions. The Infant Feeding Intentions (IFI) scale was developed to fill this need. Two items probe strength of intentions to initiate breastfeeding and subsequent items assess strength of intentions to be breastfeeding exclusively (EBF) at 1, 3, or 6 months. Total score ranges from 0 to 16. Content validity was established among women in their third trimester of pregnancy (n = 88). Subsequently, construct validity was assessed in a low-income, multi-ethnic cohort of primiparae (n = 170) interviewed at 25 +/- 15 h postpartum and followed to 6 months. Cronbach's coefficient alpha was 0.90 for both the content and construct validity samples. Construct validity was demonstrated by a significant association between IFI score and both planned and actual EBF duration: mean (+standard deviation) IFI scores were 4.6 +/- 2.9, 7.5 +/- 3.2, 10.3 +/- 2.7, 12.0 +/- 1.8, and 13.8 +/- 2.7 for planned duration of EBF of 'Never', up to 1 month, 1 to <3 months, 3 to <6 months, and > or =6 months, respectively; ANOVA, P < 0.0001; and each 1-point increase in IFI score decreased the hazard of not EBF by 23.4% at day 0 and 13.7% at day 30 (Cox proportional hazards model chi-square = 92.5, P < 0.0001). In a multi-ethnic U.S. sample of low-income primiparae, the IFI scale was shown to be a valid, simple tool for quantitatively assessing the strength of intentions to initiate and sustain EBF.


[Surgery of gastric cancer in patients older than 70 years (author's transl)].
In this study it is reported about operative mortality and long-term results of surgery of gastric carcinoma in patients over the age of 70 years. The operative mortality in 50 patients with a distal partial gastrectomy was 16%, the mortality in 24 patients with total gastrectomy was 33.3% and in 14 patients with a proximal gastrectomy the mortality was 28%. The main cause of death (40%) was a pneumonia. There was no correlation between frequency of pneumonia and preoperative results of measurement of lung function. Only advanced arteriosclerotic disease in the heart and brain has a fatal influence on mortality rate. In the old patients the long-term results are determined by the staging of the tumor at the time of operation, too. In the 60 patients, who had left the hospital and who are in our control, the half year survival rate was 78.3%, the 1-year survival rate was 58.3% and the 2-years survival rate is exceeding 41.6%. 14 patients of the 17, who are still alive and who are after 2 1/2 years again explored, are in a very good condition. In comparison with the literature it is to conclude that for the indication to surgery of gastric carcinoma there is important not only the real age of the patient but rather the biological and mental condition of the patient.


The size of the aortic arch: a suitable criterion for differentiating between congenital heart diseases with left-to-right shunt?
A retrospective study was carried out to determine whether aortic arch size can be regarded as a reliable criterion for differentiating between congenital left-to-right shunt defects. The PA and AP plain chest films of children of all age groups with ductus arteriosus persistens (DAP) (n = 91), atrial septal defect (ASD) (n = 86), ventricular septal defect (VSD) (n = 87) and a normal control group (n = 387) were used to measure the size of the aortic arch, and an aortic index (AI) was calculated from aortic arch size and the height of the eighth thoracic vertebral body. Three age classes were defined from the AI values of the control group, and the diagnostic groups in each age class were compared with each other. Enlargement of the aortic arch, as reflected in an elevated AI value, was found most frequently in DAP cases. The size of the aortic arch is, however, of varying differential diagnostic value, depending on the age group. No correlation was found between aortic arch size and the size of the left-to-right shunt in cases of DAP.


Heteroleptic Gold(I)-bisNHC complex with excellent activity in vitro, ex vivo and in vivo against endometrial cancer.
Endometrial cancer (EC), one of the most common gynaecologic malignancies, can seriously impair female health. Although great advances in EC therapy have been achieved, specific and effective drugs for the disease are still limited. Here, different types of gold(I)-NHC compounds originated from 4,5-bis (4-methoxyphenyl) imidazole were designed and synthesised to target EC. Interestingly, the heteroleptic gold(I)-bisNHC complex 10 was 10 times more toxic than cisplatin or auranofin towards Ishikawa cells. Ex vivo studies found that complex 10 was characterised with a stronger anticancer effect than auranofin in the EC organoid model. Additionally, in vivo studies showed that complex 10 possessed a stronger anticancer effect (IRT = 44.86%) than auranofin (IRT = 19.93%) in the xenograft model of EC. Mechanistically, complex 10 could suppress the expression of thioredoxin reductase (TrxR) and nuclear factor E2-related factor 2 (Nrf2) in vitro and in vivo, which are essentially involved in EC development. Collectively, our findings demonstrated that complex 10 is a gold-based complex with a strong anti-EC activity and has the potential to be regarded as a promising option for the treatment of EC.


Legionellosis presenting as singultus and external ophthalmoplegia.
We report a 71-year-old man with legionellosis, who presented with abducens nerve palsy, singultus, confusion, memory impairment, ataxia, and hyporeflexia. Legionella pneumonia was diagnosed on the basis of detection of Legionella pneumophila antigen in the urine. The cerebrospinal fluid was negative for the antigen and antibody, but an oligoclonal band was detected, and the IgG index was elevated. It was speculated that an undetermined immune-mediated mechanism had contributed to the development of the neurological manifestations.


Canine mitochondrial uncoupling proteins: structure and mRNA expression of three isoforms in adult beagles.
Uncoupling proteins (UCPs) are members of the mitochondrial transporter family that dissipate the proton gradient as heat more than via ATP synthesis. In the present study, nucleotide and amino acid sequences of UCPs 1, 2 and 3 of a dog were determined, and their mRNA expression in various peripheral tissues was examined. The sequences were highly (76-97%) homologous to those of other species. Although lower homologies (60-74%) were found when compared among the three canine UCPs, their deduced amino acid sequences had some common domains, such as three mitochondrial carrier protein motifs, six transmembrane alpha-helix domains, and putative purine nucleotide binding domains. By Northern blot analyses, UCP1 mRNA was not detected in any tissues examined. UCP2 mRNA was expressed in most tissues, particularly abundantly in adipose tissue, spleen and lung. Two sizes of UCP3 mRNA were found exclusively in heart and skeletal muscle. These results suggest that canine UCPs have uncoupling activity, and are involved in the regulation of metabolic heat production and/or energy expenditure, as do those of other species.


Alexithymia and anhedonia in early Richardson's syndrome and progressive supranuclear palsy with predominant parkinsonism.
Phenotypic variants of progressive supranuclear palsy (PSP) are all characterized by the combination of motor symptoms of parkinsonism with a number of neuropsychiatric and cognitive disorders. Despite the strong effort in characterizing these features in PSP, alexithymia and anhedonia have not been investigated at present. Here, we aimed at investigating the qualitative and quantitative differences of alexithymia and anhedonia in the two more frequent variants of PSP, Richardson's syndrome (PSP-RS) and PSP with predominant parkinsonism (PSP-P) compared to Parkinson's disease (PD) patients recruited within 24 months after the onset of motor symptoms. One hundred fifty-five PD, 11 PSP-P, and 14 PSP-RS patients underwent clinical, neuropsychiatric, and neuropsychological evaluations. Alexithymia was assessed using the Toronto Alexithymia Scale-20 item (TAS-20), and hedonic tone was measured by the Snaith-Hamilton Pleasure Scale (SHAPS). In PSP-P and PSP-RS patients, the frequency of alexithymia diagnosis was higher than in PD. On the TAS-20 scores, PSP-RS performed worse in the total score and in F2 sub-scale when compared to PD. Among patients with diagnosis of depression, PSP-RS showed higher scores in TAS-20 total and TAS-20 F2 than PD. No significant differences in TAS-20 scores were found in nondepressed patients. Finally, we did not find significant differences among PD, PSP-P, and PSP-RS groups in the SHAPS scores. Alexithymia is identifiable very early in PSP-P and PSP-RS patients. Alexithymic symptoms differentiate PSP-RS group from PD group but not between the two subtypes of PSP. Further, alexithymia in PSP seems to be predicted by the presence of depression. Altered emotional capability could be related to specific neurophysiological dysfunction occurring precociously in PSP; therefore, its identification could orient the diagnosis toward PSP cases.


What is the switch for coupling transcription and splicing? RNA Polymerase II C-terminal domain phosphorylation, phase separation and beyond.
Phosphorylation of the RNA polymerase II C-terminal domain (Pol II CTD) has important roles in the kinetic coupling of splicing with transcription, which is essential for many genes to maintain correct splicing patterns. However, because of the extensively repeated low complexity sequences of Pol II CTD, it was unclear how phosphorylation-dependent molecular interactions were able to provide sufficient specificity to spatiotemporally partition various cotranscriptional events. Here we try to view the molecular mechanisms governing cotranscriptional splicing from the role of phase separation based on recent studies showing the ability of Pol II CTD to form droplets. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Processing > Splicing Mechanisms RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.


Effectiveness of early identification and electronic interventions for teens with risk factors for the development of heart disease and diabetes.
Serum risk factors for the development of heart disease and diabetes are not routinely evaluated in teens. The intent of this study was to determine the prevalence of these risk factors in teens and evaluate the effectiveness of a two-part electronic education program (recurring electronic lifestyle education program [REEP]) on reducing risks. Teens (n = 170) were recruited from one urban and one rural high school in the mid-Atlantic in 2014. Following baseline data collection in February, REEP was initiated and data collection repeated at 12 weeks. Data were analyzed and students sent a report with results and recommendations. One or more serum and/or physical risk factors were found in the majority of students with low vitamin D and elevated body mass index (BMI) being the most common. Correlations existed between elevated BMI and elevated diastolic blood pressure, low vitamin D, and low high-density lipoprotein. All but one risk factor (BMI) improved at 12 weeks. The majority of teens had one or more physical and/or serum risk factors. Using multiple electronic methods to deliver healthy lifestyle recommendations helps lower these risks. Also, Blackboard, an electronic learning platform, was found to be an effective data management and communication center.


Novel phosphate mimetics for the design of non-peptidyl inhibitors of protein tyrosine phosphatases.
Benzylic alpha,alpha-difluorosulfonates, alpha,alpha-difluorotetrazoles, and alpha,alpha-difluorocarboxylates of type 5 and 6 were synthesized and examined as potential phosphate biosteres for PTP1B inhibition. The alpha,alpha-difluorosulfonates and alpha,alpha-difluorotetrazoles were found to be more effective inhibitors than the analogous compounds bearing the fluoromalonyl group, a phosphate biostere currently being used for PTP inhibition.


Psychological repercussions in family members of hospitalised critical condition patients.
We analysed the influence of certain variables [quality of life (QoL) and passage of time] of patients in the intensive care unit (ICU) on other variables (clinical dimensions of personality, family environment, fear of death) of their family members. Fifty-seven family members of ICU patients filled in five questionnaires when the patients stayed in the ICU, and 4 years later, the patients filled in a QoL questionnaire. The following results were obtained: (1) Passage of time has influence on Agitation, Boredom-withdrawal, Psychopathic Deviation, and Psychological Inadequacy, only in family members of patients with good QoL; (2) family members score higher in Hypochondriasis, Suicidal Depression, Agitation, Anxious Depression, Guilt-resentment, Paranoia, Psychasthenia, Psychological Inadequacy, and Expression, and lower in Fear of the process of another's dying, when the patient was in ICU than 4 years later; (3) family members of patients with bad QoL 4 years after ICU score higher in Hypochondriasis, Suicidal Depression, Agitation, Schizophrenia, Psychasthenia and Psychological Inadequacy than did the family members of patients with good QoL.


Tumor necrosis factor-α -308 G>A and interleukin-6 -174 G>C promoter polymorphisms and pemphigus.
The objective of this study was to analyze the possible involvement of the tumor necrosis factor (TNF)-α -308 G>A and interleukin-6 (IL-6) -174 G>C polymorphisms in the susceptibility and/or disease profile of pemphigus in Egyptian patients. Detection of TNF-α -308 G>A by amplification refractory mutation system and IL-6 -174 G>C by restriction fragment length polymorphism was performed for 70 patients and 203 controls. No significant differences were observed in the distribution of TNF-α -308 in pemphigus patients and controls. However, GA+AA genotypes were more frequent in pemphigus vulgaris (PV) patients only versus controls (p(c) = 0.046). The frequency of the C allele and CC/GC genotypes of IL-6 -174 was significantly higher in pemphigus patients and those with the 2 major clinical forms (PV and pemphigus foliaceus [PF]) compared with controls (p < 0.05). Comparison of the distribution of TNF-α -308 and IL-6 -174 variants in relation to clinical type of pemphigus (PV versus PF), activity score, recurrence, and demographic data of patients revealed no significant associations. The IL-6 -174 CC genotype represents a marker of increased susceptibility to pemphigus in Egyptian patients and GG genotype can be considered a low-risk genotype; TNF-α -308 A-containing genotypes contribute to the susceptibility to PV only.


Knocking down Siglec-15 in osteosarcoma cells inhibits proliferation while promoting apoptosis and pyroptosis by targeting the Siglec-15/STAT3/Bcl-2 pathway.
Sialic acid-bound immunoglobulin lectin 15 (Siglec-15) plays a crucial role in many kinds of tumors. The relationship between Siglec-15 and the prognosis of osteosarcoma patients and its role in the apoptosis and pyroptosis of osteosarcoma cells are not sufficiently understood. Our study aimed to investigate the function of Siglec-15 in osteosarcoma cells and its effect on tumor cell proliferation, apoptosis and pyroptosis. The Siglec-15 expression in pathological sections of osteosarcoma patients was analyzed and the overall survival time related to the expression of Siglec-15 was further analyzed. Next, we detected the expression of Siglec-15 in osteosarcoma cells and downregulated the expression of Siglec-15 by small interfering RNA (siRNA). The proliferation, apoptosis and pyroptosis of osteosarcoma cells were studied by proliferation and apoptosis kits and Western blotting. Furthermore, the Siglec-15 signaling pathway was examined, which may be involved in the observed cellular effects. We demonstrated the expression of Siglec-15 in osteosarcoma cells. SiRNA-mediated downregulation of Siglec-15 was successful. We found that knockdown of Siglec-15 in osteosarcoma cell lines significantly inhibited proliferation while promoting apoptosis. Further investigation showed that the expression of proliferation-related proteins was downregulated and that apoptosis- and pyroptosis-related proteins were upregulated. In addition, we found that Siglec-15 may inhibit proliferation while inducing apoptosis and pyroptosis via the (Signal Transducer and Activator of Transcription 3) STAT3/Bcl-2 pathway in osteosarcoma. In this study, we demonstrated that the ablation of Siglec-15 in osteosarcoma inhibited proliferation and promoted apoptosis and pyroptosis by targeting the Siglec-15/STAT3/Bcl-2 pathway.


Screening by nurses and junior doctors to detect malnutrition when patients are first assessed in hospital.
Four hundred and fifty four ward nurses and 319 junior doctors in 70 hospitals were interviewed about the last patient they had admitted, using a brief questionnaire. The availability of weighing scales and height measuring equipment was assessed by observers who visited the wards of 107 hospitals. Two thirds of nurses and doctors asked patients about recent food intake; half of the nurses and three quarters of the doctors asked about unintentional weight loss. Answers to the questions were recorded in the notes on 52-80 per cent of occasions. Two thirds of nurses weighed the patient, but only 11 per cent (%) measured height; approximately 80% of results were recorded. Most nurses and doctors who asked no questions about nutrition and made no measurements failed to do so because they regarded them as unimportant. Weighing scales were adequately provided, but height measuring equipment was available in only 17% of wards.


Social network analysis to study health behaviours in adolescents: A systematic review of methods.
Our objectives were (i) to systematically review how SNA is used in studies investigating adolescent health behaviours (i.e., the purpose of using SNA, methods used for network data collection and analysis), and (ii) to develop methodological guidelines to help researchers use SNA in studies on adolescent health behaviours. Five databases were searched using keywords related to "social network analysis" and "adolescents". We extracted data from included articles pertaining to the choice of methods for network data collection and analysis. We used these data to develop a 5-step decision tree to help researchers make methodological decisions most appropriate to their research objectives. A total of 201 articles were included. Most investigated tobacco (50%) or alcohol use (48%). SNA was used most often to examine processes related to peer selection or influence (37%) and/or to examine the effect of sociometric position on health behaviours (34%). 181 studies (90%) used a sociocentric approach for SNA, 16 studies (8%) used an egocentric approach, and 4 studies (2%) used both. We identified five decision-making steps in SNA including the choice of: (i) network boundary, (ii) SNA approach, (iii) methods for name generators, (iv) methods for name interpreters, and (iv) SNA indicators. This study provides insights and guidance in a 5-step decision tree on practical and methodological considerations in using SNA to explore adolescent health behaviours.


Nitrogen and water inputs to tomato plant do not trigger bottom-up effects on a leafminer parasitoid through host and non-host exposures.
Bottom-up and top-down forces are major components of biological control against pests in an agro-ecosystem. Understanding the multi-trophic interactions between plants and secondary consumers would help optimize pest control strategies. We manipulated nitrogen and/or water inputs to tomato plants (Solanum lycopersicum) to test whether these manipulations could trigger bottom-up effects on the parasitoid Necremnus tutae via host (Tuta absoluta) and/or non-host (Bemisia tabaci) exposures, and compared the control efficacy of N. tutae on T. absoluta in the presence and absence of B. tabaci. The results showed no cascading effects of plant nitrogen and/or water inputs on N. tutae via either host or non-host exposure. The bottom-up force was mitigated by chewing or sap-feeding insect consumers at the second energy level. By contrast, the top-down force on T. absoluta from parasitoids was enhanced by an additionally provided non-host, which could produce alternative food sources extending N. tutae longevity and enhancing the fitness of its offspring. Our results provided evidence for the combination of bottom-up and top-down approaches in tomato integrated pest management programs. © 2017 Society of Chemical Industry.


Haemodynamic effects of induction of epidural analgesia in labour.
The effect of induction of epidural analgesia with 0.5 per cent bupivacaine on maternal haemodynamics was investigated in 21 patients with uncomplicated full-term pregnancies in early labour. Stroke volume, heart rate, and cardiac output (SV, HR, and CO) were measured by transcutaneous aortovelography (TAV). Systolic, diastolic, and mean arterial blood pressures (SBP, DNP, and MAP) were measured by indirect automatic oscillometry. Measurements were made with the patient in the left lateral decubitus position before and after an intravenous bolus of 500 ml of lactated Ringer's solution preceding induction of epidural analgesia, and again 30 and 45 minutes after induction. The 500 ml bolus of lactated Ringer's solution did not prevent fall of CO and BP measured 30 minutes after induction, when there were statistically significant decreases in CO and cardiac index (-10.2 and -10.6 per cent, p less than 0.05), and in SBP, DBP, and MAP (-9.7, -12.5, and -11.9 per cent, p less than 0.005, p less than 0.005 and p less than 0.01 respectively). At 45 minutes after induction, CO and cardiac index had returned to baseline values. Although the decreases in SDP and DBP persisted, the change in MAP was not statistically significant.


Properties of hydric and biodegradability of cassava starch-based bioplastics reinforced with thermally modified kaolin.
In this study, hydric and biodegradability properties of cassava starch-based bioplastics reinforced with crude kaolin or treated kaolinitic clay at 700 °C called metakaolin were investigated using water adsorption and microbiological tests. Non-reinforced bioplastics (BP) and those containing 5 wt.% crude kaolin (BPKB) or metakaolin (BPMKB) were manufactured using the casting/evaporation method. Results obtained showed a decrease in the solubility and in the water diffusion and permeability of clay-reinforced bioplastics with respect to the ones without reinforcement. This improvement of the hydric properties has been attributed to the reduction in the free volumes existing between the starch macromolecules due to their interactions with clay platelets. These interactions might favor a more homogeneous and compact microstructure. The biodegradability of the clay reinforced bioplastics was significantly improved due to the bacterial proliferation. The thermal treatment of kaolinitic clay further improved the hydric and biodegradability properties of starch-based bioplastics.


Revisiting the supplementary relationship of dynamic contact angles measured by sessile-droplet and captive-bubble methods: Role of surface roughness.
Quantitative characterization of surface wettability through contact angle (CA) measurement using the sessile droplet (SD) or captive bubble (CB) methods is often limited by the intrinsic wetting properties of the substrate. Situations may arise when an extreme surface wettability may preclude using one of the two methods for predicting the behaviors of droplets or bubbles on the surface. This warrants a relationship between the dynamic CAs measured via the SD and CB methods. While the two dynamic CAs (e.g., the advancing CA of SD and receding CA of CB) add up to 180° on a smooth surface, the simple geometric supplementary principle may not apply for rough surfaces. We perform a systematic wettability characterization of solid substrates with varying degrees of roughness using the sessile-droplet and captive-bubble methods, and interpret the experimental observations using a theoretical model. The dynamic contact angles measured by the sessile-droplet and captive-bubble methods deviate from the supplementary principle as the surface roughness is increased. We present a theoretical explanation for this disparity and predict the values of the contact angles using prevalent thermodynamic models of wetting and contact-angle hysteresis on rough substrates. The theoretical prediction is in good agreement with the experimental observations.


Digital tomosynthesis of the pediatric elbow.
Imaging pediatric elbow trauma in the acute setting remains diagnostically challenging given difficult patient positioning, multiple ossification centers of the pediatric elbow, overlapping structures, and complex joint anatomy. Digital tomosynthesis is a technique where the X-ray source travels across a limited arc angle, obtaining a series of low-dose exposures that are in turn digitally reconstructed to produce high in-plane resolution at a relatively low overall radiation dose. Digital tomosynthesis is now more commonly integrated into standard radiographic machines and offers a new and exciting way to assess the pediatric elbow. In this review article we discuss the clinical applications of digital tomosynthesis in pediatric elbow trauma along with challenges related to technique, patient positioning and artifacts.


Effect of carbamylation on the molecular recognition action of amino benzothiazole by carrier protein.
Increasing benzothiazole derivatives containing amino or N-acyl structures in position 2 have been largely developed as pesticides and medicines. However, the structure-function relationship of 2-substituted benzothiazole derivatives has seldom been illustrated from the perspective of their albumin-binding nature. Herein, to probe the influence of carbamylation on the albumin-binding nature of benzothiazole derivatives, formyl group was introduced to the amine group of 2-amino benzothiazole (ABT) to yield a novel modified ABT (MABT). Their protein-binding properties were systematically deciphered by spectroscopy, molecular modeling and density functional theory (DFT) calculations. The interaction mechanisms, recognition thermodynamics and binding geometry were investigated and compared. The structural alteration of human serum albumin was explored using synchronous fluorescence emission and circular dichroism spectrum technologies. Based on experimental results, the structures of protein complex with MABT and ABT were revealed by molecular docking method. The differences in energy transfer efficiency and molecular orientation of ABT and MABT in new complexes were tentatively explained by DFT calculations. The work was expected to help to understand the impact of different substituents on the bioactivity of benzothiazole derivatives and guide for structural designs of new compounds.


Rescue of human corneal epithelial cells after alkaline insult using renalase derived peptide, RP-220.
To study the effect of renalase peptide, RP-220, on cell viability of human corneal epithelial cells after alkali insult. A dose-response relationship between cell viability and exposure to NaOH solution were characterized using cultured human corneal epithelial cells. Viability of corneal epithelial cells was determined using commercially available MTT and CyQUANT® assays. At a concentration of 6 mmol/L, insult with NaOH leads to reduced corneal epithelial cell viability by approximately 30%. This reduced viability was prevented by treating the cells after initial insult with the 20-amino acid renalase derived peptide (RP-220). RP-220 has a pro-survival role for RP-220 following alkaline insult to corneal epithelial cells.


1,3-diarylpyrazolones as potential anticancer agents for non-small cell lung cancer: Synthesis and antiproliferative activity evaluation.
A series of pyrazolone compounds with different substitution patterns have been synthesized using microwave-assisted methods and evaluated their in vitro antiproliferative activity against human lung adenocarcinoma cell lines (A549 and NCI-H522). Among the tested compounds, the pyrazolone P7 exhibited high antiproliferative activity against both A549 and NCIH522 cancer cell lines while being 10 times less cytotoxic to non-cancerous cells. Moreover, our compounds P7 and P11 exhibited higher antiproliferative activity and selectivity against A549 and NCIH522 cells compared with the clinically approved drugs Afatinib and Gefitinib. The cell cycle analysis showed that the compound P7 and P11 arrests the cell cycle at G0/G1 phase, whereas the compounds P13 and P14 involved in G2/M phase arrest. The results from antiproliferative activity screening, cell cycle analysis, and kinase profiling indicate that the suitably substituted 1,3-diarylpyrazolones exhibit high antiproliferative activity against non-small cell lung cancer cells.


The KCNH2 genetic polymorphism (1956, C>T) is a novel biomarker that is associated with CCB and α,β-ADR blocker response in EH patients in China.
KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies. To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out. There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed. We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs.


Sensitivity of ICD coding for sepsis in children-a population-based study.
International Classification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease. To describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome. Secondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland. We compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals. We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37-50). Agreement of ICD-10 coding abstraction with validated study data varied by the underlying infection type and disease severity (p < 0.05). The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data. In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease. The online version contains supplementary material available at 10.1007/s44253-023-00006-1.


Evidence of the direct adsorption of mercury in human hair during occupational exposure to mercury vapour.
We have found clear evidence of direct adsorption of mercury in human hair after the occupational exposure to mercury vapour. We have performed both longitudinal analysis of human hair by laser ablation ICP-MS and speciation analysis by gas chromatography ICP-MS in single hair strands of 5 individuals which were occupationally exposed to high levels of mercury vapour and showed acute mercury poisoning symptoms. Hair samples, between 3.5 and 11cm long depending on the individual, were taken ca. three months after exposure. Single point laser ablation samples of 50μm diameter were taken at 1mm intervals starting from the root of the hairs. Sulfur-34 was used as internal standard. The ratio (202)Hg/(34)S showed a distinct pattern of mercury concentration with much lower levels of mercury near the root of the hair and high levels of mercury near the end of the hair. In all cases a big jump in the concentration of mercury in hair occurred at a given distance from the root, between 32 and 42mm depending on the individual, with a high and almost constant concentration of mercury for longer distances to the root. When we took into account the rate of hair growth in humans, 9-15mm/month, the jump in mercury concentration agreed approximately with the dates when the contamination occurred with the new growing hair showing much lower mercury concentration. In some cases the concentration of mercury at the tip of the hair was ca. 1000 times higher than that near the root. Additionally, speciation studies confirmed that mercury in all hair samples was present as inorganic mercury. The only explanation for these results was the direct adsorption of mercury vapour in hair at the time of exposure.


MRI of "diffusion" in the human brain: new results using a modified CE-FAST sequence.
"Diffusion-weighted"MRI in the normal human brain and in a patient with a cerebral metastasis is demonstrated. The method employed was a modified CE-FAST sequence with imaging times of only 6-10 s using a conventional 1.5-T whole-body MRI system (Siemens Magnetom). As with previous phantom and animal studies, the use of strong gradients together with macroscopic motions in vivo causes unavoidable artifacts in diffusion-weighted images of the human brain. While these artifacts are shown to be considerably reduced by averaging of 8-16 images, the resulting diffusion contrast is compromised by unknown signal losses due to motion.


SMAD2 inhibits pyroptosis of fibroblast-like synoviocytes and secretion of inflammatory factors via the TGF-β pathway in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease. Over-activation of fibroblast-like synoviocytes is responsible for the hyperplasia of synovium and destruction of cartilage and bone and pyroptosis of FLS plays a key role in those pathological processes during RA. This study investigated the detailed mechanisms that SMAD2 regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis. We collected synovial tissues of RA patients and FLS-RA and cultured FLS for detection of expression of SMAD2. ASC, NLRP3, cleaved-caspase-1, and GSDMD-N were detected by Western blot after overexpression of SMAD2. Besides, flow cytometry, electron microscope, ELISA, HE staining, and Safranin O staining were performed to further demonstrate that SMAD2 can affect the pyroptosis of FLS-RA. The expression of SMAD2 was down-regulated in synovial tissues of RA patients and FLS-RA. Overexpression of SMAD2 can inhibit the expression of ASC, NLRP3, cleaved-caspase-1, and GSDMD-N. Flow cytometry and electron microscope further demonstrated that SMAD2 attenuated pyroptosis of FLS-RA. In addition, overexpression of SMAD2 also inhibited inflammatory factors such as IL-1β, IL-18, IL-6, and IL-8 secretion and release of LDH. Besides, overexpression of SMAD2 can reverse the decrease of p-SMAD2 and TGF-TGF-β induced by nigericin. In vivo experiments on CIA rats further demonstrated that overexpression of SMAD2 by local intra-articular injection of LV-SMAD2 can effectively alleviate joint redness, swelling, and destruction of cartilage and bones. SMAD2 inhibited FLS-RA pyroptosis by down-regulating of NLRP3 inflammasomes (NLRP3, ASC, and caspase-1 complex) and eased the secretion of inflammatory factors via the TGF-β signaling pathway, thereby improving the symptom of RA. We hope that this study may provide a new research idea for RA and a potential target for the treatment of RA.


Transfusional transmitted virus seroprevalence in asymptomatic HBsAg (+) hepatitis B carriers.
The aim of this study was to evaluate the transfusional transmitted virus (TTV) seroprevalence in asymptomatic HBsAg (+) patients and to assess the influence of TTV on the course of these patients. Sixty asymptomatic HBV carriers were included and 31 healthy volunteers served as controls. Cases were followed at 6-month intervals for a total duration of 4 years. In the asymptomatic carrier group, 31 patients (51.7%) had a history of surgery and 10 (16.7%) had a history of blood transfusions. TTV-DNA was detected in 45 of these patients (75%). In the control group, 12 patients (38.7%) had a history of surgery and 2 had (6.5%) a history of blood transfusions. TTV-DNA was found in 20 (64.5%) of these subjects. The incidence of TTV-DNA positivity was not significantly different between the two groups (P > 0.05). In spite of the common occurrence of HBV and TTV, TTV-DNA was also detected in 64.5% of healthy controls. Furthermore, during 4 years of follow up, TTV had no detrimental effects on the course of asymptomatic HBV carriers. These results suggest that the hepatic injury due to TTV is insignificant in this group of patients.


Health care prioritization in ageing societies: influence of age, education, health literacy and culture.
To examine how Chinese people in Hong Kong view health care prioritization and to compare the findings with those from a United Kingdom survey. A cross-sectional opinion survey was conducted in Hong Kong and 1512 participants were interviewed. Data show that the highest rankings were accorded to "treatment for children" and "high technology services." Services for the elderly, whether in the community or in hospitals, and including end-of-life care, were ranked among the lowest. This view was also shared by healthcare professionals. Compared with the UK findings, there are stark contrasts in the low ranking of end-of-life care and the high ranking of high technology services among the HK population. It is evident that most people would give priority to the young over the old in distributing a given amount of healthcare services. To meet the needs of ageing societies and to meet the needs of all users equitably, health care policy needs to acknowledge constraints and the needs for prioritization. Both the public and professionals should engage with policy makers in formulating a policy based on cost benefit considerations as well as overall societal view of prioritization that is not based on age alone.


[Nursing care for tracheotomy and tracheostomy patients].
Nursing care is specific in otorhinolaryngology, particularly in oncology. The three dimensions of the care, technical, relational and educational, are essential and reflect the quality of the patient management which must be multi-disciplinary.


The need for national mandatory guidance on CSTDs.
Closed system transfer devices play a vital role in reducing health professionals' risk of exposure to hazardous drugs. Although recommended as a first line of defence against contamination, they are not widely used. Clear mandatory national guidance is needed to address this.


Wavelength dependence of ultraviolet light inactivation for SARS-CoV-2 omicron variants.
Ultraviolet (UV) irradiation offers an effective and convenient method for the disinfection of pathogenic microorganisms. However, UV irradiation causes protein and/or DNA damage; therefore, further insight into the performance of different UV wavelengths and their applications is needed to reduce risks to the human body. In this paper, we determined the efficacy of UV inactivation of the SARS-CoV-2 omicron BA.2 and BA.5 variants in a liquid suspension at various UV wavelengths by the 50% tissue culture infection dose (TCID50) method and quantitative polymerase chain reaction (qPCR) assay. The inactivation efficacy of 220 nm light, which is considered safe for the human body, was approximately the same as that of health hazardous 260 nm light for both BA.2 and BA.5. Based on the inactivation rate constants determined by the TCID50 and qPCR methods versus the UV wavelength, the action spectra were determined, and BA.2 and BA.5 showed almost the same spectra. This result suggests that both variants have the same UV inactivation characteristics.


Brain as the house of autistic soul: current trends in analyzing the risk factors and building up the diagnosis in mild forms of autism spectrum disorder.
The number of children with Autism Spectrum Disorder (ASD) has significantly increased over the last few years. On the one hand, this surge may be associated with increased awareness of this entity and the greater availability of diagnostic tools. On the other hand, influence of factors believed to cause or facilitate ASD development (including environment pollution, stress of modern civilization, brain trauma and use of drugs) could have a negative impact on individuals in the phase of their social and psychological development. Due to the increasing problem, more and more attention is being focused on early detection of ASD, what allows to intervene at the earliest time point. In consequence, the quality of life of ASD-affected people may be significantly improved if diagnosed early. In this review, the list of possible risk factors for ASD is critically appraised and some "pearls for practice", helping in early diagnosis of even mild ASD are outlined.


Prospective Validation of the Ottawa 3DY Scale by Geriatric Emergency Management Nurses to Identify Impaired Cognition in Older Emergency Department Patients.
Assessment of older emergency department (ED) patients with cognitive impairment is challenging because few tools exist that can be quickly administered by front-line practitioners. Our objective is to validate the Ottawa 3DY Scale, a 4-question screening tool for cognitive impairment, in older ED patients and compare its performance with that of the Animal Fluency Test. We conducted a prospective cohort study in 2 EDs and enrolled a convenience sample of patients aged 75 years or older with no history of cognitive impairment. Eligible patients were assessed by geriatric emergency management nurses who administered the Mini-Mental State Examination, ordered with the Ottawa 3DY Scale questions first, followed by the Animal Fluency Test. Mini-Mental State Examination score less than 25 was our criterion standard for cognitive impairment. Study patients (N=238) had a mean age of 81.9 years and were 60.1% women, and 26.5% were admitted to the hospital. The Ottawa 3DY Scale and Mini-Mental State Examination were in agreement for 75.6% of cases, with a sensitivity of 93.8% (95% confidence interval [CI] 77.8% to 98.9%) and specificity of 72.8% (95% CI 66.1% to 78.7%). The Animal Fluency Test score less than 15 and Mini-Mental State Examination score were in agreement for 46.2% of cases, with sensitivity 90.6% (95% CI 73.8% to 97.5%) and specificity 39.3% (95% CI 32.7% to 46.4%). Both the Ottawa 3DY Scale and the Animal Fluency Test demonstrated excellent sensitivity versus the Mini-Mental State Examination; however, the Animal Fluency Test exhibited poor specificity. The Ottawa 3DY Scale is an effective tool to screen for cognitive impairment in older ED patients, and its use may facilitate improved care in this vulnerable population.


Cloning and characterization of an n-alkane-inducible cytochrome P450 gene essential for n-decane assimilation by Yarrowia lipolytica.
A gene encoding cytochrome P450 involved in n-alkane utilization was cloned from an n-alkane assimilating yeast, Yarrowia lipolytica CX161-1B. The RT-PCR was performed on the mRNA prepared from the cells grown on n-alkane as a template using degenerated PCR primers designed for the conserved amino acid sequences of the CYP52 family. The RT-PCR amplified fragment was then used as a probe to isolate genes coding for P450 of the CYP52 family from the genomic DNA library of the strain CX161-1B. The nucleotide sequence of one of the positive clones was determined. An open reading frame which had the same nucleotide sequence as the RT-PCR-amplified fragment was identified. It was of 523 amino acid residues, 60.2 kDa in molecular mass, and had 30-45% sequence identity with the other members of the CYP52 family of Candida species so far analysed. The expression of the P450 gene that was named as YlALK1 was induced by n-tetradecane and repressed by glycerol. A YlALK1 gene disruptant did not grow well on n-decane, but grew on longer-chain n-alkanes such as hexadecane as a sole carbon source. Introduction of YlALK1 on a plasmid to the disruptant restored the decane assimilation. These results suggest that the YlALK1 gene product is the major P450A1k to metabolize short-chain n-alkanes such as decane and dodecane in Y. lipolytica.


[In search of the true dosage: statistics applied to the analysis of the cocaine].
A method of separation by gas chromatography with a flame ionization detector was developed for quantifying cocaine in powders seized by the police. The method was validated by studying parameters of calibration, trueness, precision based on trueness error (or systematic bias) and random error. Total error, which is the combination of these errors, is used to confirm the method adequacy with the objectives fixed by the analyst. Accuracy profile is an efficient decision tool to do it. Results obtained with weighted regression model allow concluding that the method fits quantitation of heroin and cocaine in powders on 2 to 100% concentration (w/w) domain with 10% limits of acceptation and a risk of 5%.


Nitrates: why and how should they be used today? Current status of the clinical usefulness of nitroglycerin, isosorbide dinitrate and isosorbide-5-mononitrate.
Nitrates are highly effective both in terminating acute attacks of angina pectoris and in the prophylaxis of symptomatic and asymptomatic myocardial ischemia. Preload reduction by venodilatation is the prevailing mechanism of nitrates in patients with chronic stable angina and is the unique feature distinguishing them from beta and calcium-channel blockers. Nitrates dilate coronary arteries not only in pre- and poststenotic vessels, but also in eccentric lesions. In patients with endothelial dysfunction, nitrates seem to be the physiological substitute for endothelium-derived relaxing factor. During the past decade, however, there has been substantial evidence of a clinically relevant loss of the anti-ischemic effects ("nitrate tolerance"). Many studies with oral dosing of isosorbide dinitrate or isosorbide-5-mononitrate at least three times daily have proven nitrate tolerance in patients with coronary artery disease and/or congestive heart failure. Complete loss of anti-ischemic effects after repetitive, continuous patch attachments has also been found. As we first showed in 1983, intermittent therapy with once-daily ingestion of high-dose sustained-release isosorbide dinitrate was successful in preventing the development of tolerance. Similarly, tolerance to isosorbide-5-mononitrate also does not develop when it is ingested once daily. It is now generally accepted that a daily low-nitrate interval is required to prevent tolerance development. Although the minimal patch-free interval required to prevent tolerance needs further investigation, a 12-h patch-free interval should prevent tolerance in most patients. The prolonged duration of action of once-daily high-dosage administration of sustained-release formulations, the improved patient compliance with a single daily administration, and the increased likelihood of maximal anti-ischemic effects are important reasons for recommending high single daily doses of isosorbide dinitrate or isosorbide-5-mononitrate.


Short and long term changes in carbon, nitrogen and acidity in the forest soils under oak at the Alice Holt Environmental Change Network site.
The dynamics of soil properties within a 70 year old oak plot were assessed every five years (1994-2009), by depth and by horizon to identify short term changes in soil carbon and nitrogen stocks, and acidity. The findings were set within a study of long term changes in soil properties in a 180 year chronosequence of oak plots from the same forest. Carbon stock increased significantly in the top mineral horizon - overall increase was 5 t C ha(-1), at a mean accumulation rate of 0.34 t C ha(-1)y(-1), which was mainly due to increase in horizon thickness. No increase was seen when soils were sampled by depth. Differences obtained by depth or horizon sampling due to changes in horizon thickness over time highlight the importance of horizon in the correct evaluation of soil property change in small scale sampling programs. This is particularly important in forest soils with high litter accumulation and low turnover rates when compared to other land uses. Nitrogen stock increases below 10cm soil depth were attributed to insect activity, litterfall variation and a change in water table. Findings were confirmed in the chronosequence study of oak across the forests; increases in soil C stocks of 0.1-0.2 t C ha(-1)y(-1) were calculated across young (~25 years), mid-rotation (~60 years) and old (120+ years) stands. Soil nitrogen increased significantly with canopy age whilst pH increased significantly between young-mid rotation stands but decreased between mid rotation and old stands. Significant increases in pH were also recorded before 2004 in the ECN 70 year old oak plots reflecting overall pollution recovery.


Collective Motion in Human Crowds.
The balletic motion of bird flocks, fish schools, and human crowds is believed to emerge from local interactions between individuals, in a process of self-organization. The key to explaining such collective behavior thus lies in understanding these local interactions. After decades of theoretical modeling, experiments using virtual crowds and analysis of real crowd data are enabling us to decipher the 'rules' governing these interactions. Based on such results, we build a dynamical model of how a pedestrian aligns their motion with that of a neighbor, and how these binary interactions are combined within a neighborhood in a crowd. Computer simulations of the model generate coherent motion at the global level and reproduce individual trajectories at the local level. This approach yields the first experiment-driven, bottom-up model of collective motion, providing a basis for understanding more complex patterns of crowd behavior in both everyday and emergency situations.


Glycaemic response and hydrogen production to blenderised and polymeric enteral nutrition formulas.
Complete enteral nutrition preparations include blenderised formulas based on natural foods with some fibre content and also low-residue polymeric formulas. This study examines the effect of the different fibre content of two commercial formulas (6.4 g/l and 0.25 g/l) on glycaemic and insulin response and hydrogen production in the colon during constant rate administration in 11 normal subjects. No difference in serum glucose and insulin levels was found. No rise in hydrogen production was detected with either formula suggesting no carbohydrate malabsorption. The quantity or nature of fibre present in blenderised formulas does not modify the pattern of carbohydrate absorption compared to a low-residue polymeric formula. However, this does not preclude other possible physiological effects of fibre content upon gastrointestinal motility and function.


Lipopolysaccharide augments venous and arterial thrombosis in the mouse.
Animal models of diseases are essential for therapeutic target validation, drug discovery and development. Increasing evidence has demonstrated the importance of inflammation in thrombosis. Here, murine models of vena cava thrombosis and carotid arterial thrombosis augmented by lipopolysaccharide (LPS) were established and characterized to study the association between inflammation and thrombosis. Murine (C57BL/6 mice) models of ferric chloride (FeCl(3))-induced carotid arterial and vena cava thrombosis were established. Thrombus formation was measured indirectly by Doppler blood flow (i.e., clot functional interference with blood flow) in the arterial thrombosis model and directly by protein content of the clot in the venous thrombosis model. An optimal concentration of FeCl(3) was defined to induce thrombus formation and used to study the effects of LPS (i.e., a well-known inflammatory stimulus under these conditions). Real-time polymerase chain reaction (PCR) was used to examine the effect of LPS on TNFalpha and IL-1beta mRNA expression in thrombus formation. Dose-dependent analysis demonstrated that 2 mg/kg, i.p., LPS provided a maximal prothrombotic effect in 2.5% ferric chloride-induced vena cava thrombosis, with a 60% increase in thrombus size (n=8, p<0.05) compared to vehicle treatment. In contrast, 2 mg/kg LPS had no significant effect on thrombus formation in a more severe, 3.5% FeCl(3)-induced vena cava thrombosis. A similar prothrombotic effect was observed for LPS in 2.5% FeCl(3)-induced carotid arterial thrombosis model. Treatment of 2 mg/kg LPS significantly augmented arterial thrombosis immediately (between 5-30 minutes) following FeCl(3) injury as assessed by change of Doppler blood flow (n=8, p<0.05). Real-time PCR demonstrated significant induction of TNFalpha and IL-1beta mRNA expression in the thrombus formation in the vessels in response to LPS challenge. These data demonstrate that LPS augments thrombus formation in acute vascular injury and that LPS-augmented thrombosis might be a useful tool to study the relationship between inflammation and thrombosis.


Constitutive activation of MEK1 in osteoprogenitors increases strength of bone despite impairing mineralization.
Recent clinical studies have revealed that a somatic mutation in MAP2K1, causing constitutive activation of MEK1 in osteogenic cells, occurs in melorheostotic bone disease in humans. We have generated a mouse model which expresses an activated form of MEK1 (MEK1DD) specifically in osteoprogenitors postnatally. The skeletal phenotype of these mice recapitulates many features of melorheostosis observed in humans, including extra-cortical bone formation, abundant osteoid formation, decreased mineral density, and increased porosity. Paradoxically, in both humans and mice, MEK1 activation in osteoprogenitors results in bone that is not structurally compromised, but is hardened and stronger, which would not be predicted based on tissue and matrix properties. Thus, a specific activating mutation in MEK1, expressed only by osteoprogenitors postnatally, can have a significant impact on bone strength through complex alterations in whole bone geometry, bone micro-structure, and bone matrix.


[Genetic effects induced by nickel sulfate in germline and somatic cells of WR mice].
We examined the effects of nickel sulfate at doses 0.5 to 5.0 mg/kg (LD50) on the frequency of dominant lethal mutations and two-strand DNA breaks (TSBs) in germline cells and on an increase in frequency in gene mutations W(y) in pigment cells of first-generation mice. The results indicated that spermatogenesis stages most sensitive to nickel sulfate (at a dose of 1.0 mg/kg) are spermatozoids, early spermatids, late spermatocytes, and stem spermatogonia. No statistically significant increase in the total TSB level was detected in spermatozoids 4 weeks after exposure. At the same time, a significant (P < 0.05) increase in percentage of cells with an extremely high level of DNA fragmentation (supposedly apoptotic cells) was observed upon exposure at a dose of 0.5 mg/kg. Nickel sulfate at doses of 5.0 and 1.0 mg/kg induced a marked increase in the c-kit gene expression in pigment cells of heterozygous first-generation WR mice as compared to control (P < 0.001). It was shown that the nonobservable adverse effect level (NOAEL) of nickel sulfate on the dominant lethal mutation frequency and gene mutations was 1/200 LD50, while the lowest observable adverse effect level (LOAEL) was 1/100 LD50.


Preliminary experience with endoscopic stent placement in benign pancreatic diseases.
We treated 35 patients with endoscopic stent placement across the major or minor papilla in an attempt to relieve suspected partial obstruction to pancreatic duct drainage in patients with pancreatitis. The patients subsequently have been followed for periods ranging from 6 months to 3 years (mean, 14 months). Endoscopic stents were successfully placed across the minor papilla in 19 of 22 patients with pancreas divisum associated with acute recurrent pancreatitis (19) and severe abdominal pain (3). 17 patients had symptomatic improvement manifested by a decrease in frequency of attacks of pain and emergency admission. Stents were placed through the major papilla in 14 of 15 patients with recurrent pancreatitis related to a variety of causes. 8 of the 14 patients improved during the follow-up period, including 4 of 5 patients with alcoholic pancreatitis complicated by a segmental stricture.


Recycling of polluted dredged sediment - Building new materials for plant growing.
The worldwide concern is caused by a large quantity of dredged sediment. The issue becomes more severe when contaminated sediment has to be landfilled. Therefore, researchers involved in the dredged sediment management are increasingly motivated to improve circularity in sediment management processes. Prior to the dredged sediment usage in agriculture, its necessary to confirm conclusively its safety in the context of trace elements (TEs) levels. This study reports the use of different solidification/stabilization (S/S) sediment amendments (cement, clay, fly ash and green synthetized nano-zerovalent iron-nZVI) to remediate dredged sediment. The aim was to identify the effects of applied sediment S/S treatments on the growth and development of Brassica napus. The results showed that in all S/S mixtures TEs levels in the highly labile and bioavailable fraction were significantly decreased (less than 10%, while untreated sediment contained up to 36% of TEs). Simultaneously, the highest share of metals (69-92%) was in the residual fraction, which is considered as chemically stable and biologically inert fraction. Nevertheless, it was noticed that different S/S treatments trigger plants' functional traits indicating that plants' establishment in S/S treated sediment can be limited to certain extent. Besides, based on primary and secondary metabolites (elevated specific leaf area along with declined malondialdehyde content) it was concluded that Brassica plants employ a conservative resource use strategy aiming to buffer phenotypes against stress condition. Lastly, it was inferred that among all analyzed S/S treatments, green synthetized nZVI from oak leaves can effectively promote TEs stabilization in dredged sediment, concurrently enabling plant's establishment and fitness.


DNA microsatellite markers for Swartzia glazioviana (Fabaceae), a threatened species from the Brazilian Atlantic Forest.
Development and characterization of a set of DNA microsatellite markers for Swartzia glazioviana (Fabaceae), a naturally rare and threatened tree species, were carried out to investigate its conservation genetics. Through an enriched genomic library procedure, 10 DNA microsatellite loci were isolated and characterized for the species. The mean expected heterozygosity was 0.776 (0.424-0.894). Cross-species amplifications of these loci were successfully tested for six congener taxa (S. apetala var. apetala, S. flaemingii, S. langsdorffii, S. macrostachya, S. myrtifolia var. elegans, and S. simplex var. continentalis). The 10 polymorphic microsatellite markers developed are quite informative and will provide a valuable resource to study the population and conservation genetics of S. glazioviana and other Swartzia species.


Characterization and clinical verification of immune-related genes in hepatocellular carcinoma to aid prognosis evaluation and immunotherapy.
Immune-related genes (IRGs) have been confirmed to play an important role in tumorigenesis and tumor microenvironment formation in hepatocellular carcinoma (HCC). We investigated how IRGs regulates the HCC immunophenotype and thus affects the prognosis and response to immunotherapy. We investigated RNA expression of IRGs and developed an immune-related genes-based prognostic index (IRGPI) in HCC samples. Then, the influence of the IRGPI on the immune microenvironment was comprehensively analysed. According to IRGPI, HCC patients are divided into two immune subtypes. A high IRGPI was characterized by an increased tumor mutation burden (TMB) and a poor prognosis. More CD8 + tumor infiltrating cells and expression of PD-L1 were observed in low IRGPI subtypes. Two immunotherapy cohorts confirmed patients with low IRGPI demonstrated significant therapeutic benefits. Multiplex immunofluorescence staining determined that there were more CD8 + T cells infiltrating into tumor microenvironment in IRGPI-low groups, and the survival time of these patients was longer. This study demonstrated that the IRGPI serve as a predictive prognostic biomarker and potential indicator for immunotherapy.


The GPI-Linked Protein LY6A Drives AAV-PHP.B Transport across the Blood-Brain Barrier.
Efficient delivery of gene therapy vectors across the blood-brain barrier (BBB) is the holy grail of neurological disease therapies. A variant of the neurotropic vector adeno-associated virus (AAV) serotype 9, called AAV-PHP.B, was shown to very efficiently deliver transgenes across the BBB in C57BL/6J mice. Based on our recent observation that this phenotype is mouse strain dependent, we used whole-exome sequencing-based genetics to map this phenotype to a specific haplotype of lymphocyte antigen 6 complex, locus A (Ly6a) (stem cell antigen-1 [Sca-1]), which encodes a glycosylphosphatidylinositol (GPI)-anchored protein whose function had been thought to be limited to the biology of hematopoiesis. Additional biochemical and genetic studies definitively linked high BBB transport to the binding of AAV-PHP.B with LY6A (SCA-1). These studies identify, for the first time, a ligand for this GPI-anchored protein and suggest a role for it in BBB transport that could be hijacked by viruses in natural infections or by gene therapy vectors to treat neurological diseases.


Nitroxoline (8-hydroxy-5-nitroquinoline) is more a potent anti-cancer agent than clioquinol (5-chloro-7-iodo-8-quinoline).
Clioquinol has been shown to have anticancer activity both in vitro and in vivo. The present study compared the cytotoxicity of clioquinol with six analogues using human cancer cell lines. Of the analogues tested, 8-hydroxy-5-nitroquinoline (NQ) was the most toxic, with an IC(50) that was five to ten fold lower than that of other congeners. Its activity was enhanced by copper, but not zinc, and the use of a zinc-sensitive fluorophore showed that unlike clioquinol, NQ is not a zinc ionophore. NQ increased intracellular reactive oxygen species generation, an effect that was significantly enhanced by the addition of copper at levels approximately the same as those found in human plasma. NQ has been used in humans for the treatment of urinary infections. NQ is an 8-hydroxyquinoline derivative that is more potent than the halogenated 8-hydroxyquinolines, and it may be less neurotoxic because it lacks zinc ionophore activity. NQ is another clinically used anti-microbial agent whose properties suggest that it may be useful in treating cancer.


Conformational characterization of the mammalian-expressed SARS-CoV-2 recombinant receptor binding domain, a COVID-19 vaccine.
The COVID-19 pandemic has caused a large number of diseases worldwide. There are few vaccines to constrain this disease and the value of them is high. In this sense, the antigens of the vaccine platform Soberana, the receptor binding domain from SARS-CoV-2 Spike protein, both the monomeric (mRBD) and dimeric (dRBD) forms, have been developed. This study encompassed several analyses by different techniques like circular dichroism (CD), fluorescence spectroscopy (FS) and Gel Filtration- High Performance Liquid ChLC of mRBD and dRBD. Monomer and dimer exhibited similar far-UV CD spectral characteristics with 54% of β-sheet content. Similar conformational features according to near-UV CD and FS studies were observed in both RBD. Stress stability studies by far-UV CD, FS, biological activity and GF-HPLC at 37 °C showed that mRBD is very stable. On the other hand, dRBD fluorescent emission showed a shift towards higher wavelengths as the incubation time increases, suggesting exposition of tryptophan residues, unlike what happens with mRBD. Biological activity outcome confirms these results. GF-HPLC profiles showed that in mRBD, the product of molecular stress are dimers and does not increase over time. However, dRBD showed dimer fragmentation as the main degradation species. This study reveals the usefulness of CD techniques for the analysis of degradation of RBD molecules as well as showed the difference in stability of both RBD molecules. Besides, our work provides useful insights into the production of a key protein used in diagnosis and therapeutics to fight COVID-19 pandemia.