Effect of purified human interleukin-1 on cartilage degradation.
The effects of highly purified human monocyte-derived interleukin-1 (IL-1) on bovine nasal cartilage breakdown were investigated. Cartilage degradation was determined by quantifying the fraction of total proteoglycan released from cartilage during 8 days of culture. The response appeared to be chondrocyte-dependent, for IL-1 stimulated proteoglycan (PG) release from living but not from dead (frozen-thawed) cartilage. IL-1 action on living cartilage was heat labile and concentration dependent, with significant effect at 5 U/ml and maximal effect at 10-20 U/ml. Kinetic studies showed significant stimulation of PG release by 3 days of incubation with 10 U/ml IL-1. Studies in which IL-1 was removed on day 1 or day 4 showed that the cartilage-degrading effect of this monokine was reversible. Although IL-1 caused little change in the Sepharose CL-2B chromatographic profile of released PGs using an associative elution buffer, a significant shift to lower mol wt was observed under dissociative conditions. To probe the mechanism of IL-1 action, cartilage samples were incubated with IL-1 in the presence of the protein synthesis inhibitor, cycloheximide, or the lysosomal membrane-stabilizing steroid, hydrocortisone. Cycloheximide at 5-10 micrograms/ml completely blocked IL-1-induced breakdown. One the other hand, 3 x 10(-7) M hydrocortisone had little or no effect on IL-1 action. IL-1 was also shown to stimulate the degradation of human articular cartilage.


Hydraulic lift and water use by plants: implications for water balance, performance and plant-plant interactions.
During drought periods, sugar maple (Acer saccharum) demonstrates "hydraulic lift"; nocturnal uptake of water by roots from deep soil layers that is released from shallow roots into upper soil layers. Using standard water relations methods and stable hydrogen isotope analysis of both source-water and plant-water, I investigated (1) the magnitude and radial extent of hydraulic lift by mature, relatively open-grown trees, of A. saccharum, (2) the proportion of hydraulically-lifted water (HLW) used by shallow-rooted neighbors growing at different distances from target trees, and (3) the influence that this water source had on stomatal conductance to water vapor (g), water balance and growth of these neighbors. Soil water potentials (ψs) at -20 and -35 cm showed a distinct diel fluctuation. Soil pits dug beneath three mature trees revealed a distinct hard-pan (e.g. fragipan) layer at a depth of approximately 50 cm. Examination of root distributions obtained from soil cores and soil pits revealed that some larger diameter roots (1.9-3.7 cm) did penetrate the fragipan and were established in the ground water table. The presence of the fragipan indicated that the "rewetting" of the upper soil layer during the night could not be explained by capillary rise from the shallow water table; it was the trees that were taking up ground water and then redepositing it at night into the upper 35 cm of soil, above the fragipan. The greatest fluctuations in ψs occurred within 2.5 m of trees and only extended out to approximately 5 m. Application of a two-end-member linear mixing model which used stable hydrogen isotopic data obtained from environmental water sources and xylem-sap demonstrated that all neighbors used some fraction (3-60%) of HLW supplied by sugar maple trees. Plants that used a high proportion of HLW (e.g. rhizomatous or stoloniferous perennials) maintained significantly higher leaf water potentials and g, and showed greater aboveground growth when compared with (i) neighbors that used little or no HLW or (ii) conspecifics found growing at distances greater than about 3 m away from maple trees. Three important conclusions can be drawn from the results of this investigation that have not been demonstrated before: (1) hydraulic lift need not only occur in arid or semi-arid environments where chronic water deficits prevail, but can be important in relatively mesic environments when subjected to periodic soil water deficits, (2) that plants neighboring trees which conduct hydraulic lift can use a significant proportion of this water source, and (3) that the HLW source can effectively ameliorate the influence of drought on the performance and growth of neighboring vegetation. The results are also discussed in terms of their influence on plant nutrient relations (including plant-mycorrhizal associations), the nature of plant-plant interactions and the water balance of individuals, communities and floristic regions.


The unique regulation of implant surface nanostructure on macrophages M1 polarization.
The inflammatory response is the first and inevitable event after implant surgery in vivo, in which the macrophages M1 polarization is mediated. Numerous publications indicate that the physical properties of implant surface nanostructure can influence macrophages M1 polarization status, whereas the regulation mechanisms have not been elucidated yet. Unlike the conventional biochemical factors that can directly bind to the cellular surface receptors or be transported into cytoplasm, the physical information of implant surface nanostructure can only be sensed by direct contact with cells. Therefore, we infer that the implant surface nanostructure may have unique regulation mechanisms. In this study, we compared the influences of the titanium implant surface coated with titania nanotubes on the surface (∼100 nm diameter, NT-100) and the standard IFN-γ/LPS stimulation on the macrophages M1 polarization. Both the NT-100 surface and IFN-γ/LPS stimulation could induce macrophages M1 polarization, indicated by significant upregulation of M1-specific molecules including CD86, iNOS, CCR7 and IL-1β, without affecting the M2-specific molecules including CD206, Arg1 and IL-10. However, we found that the IFN-γ/LPS induced macrophages M1 polarization was mediated by RBP-J-IRF8 pathway, whereas the NT-100 surface was more related to FAK-MAPKs pathway, particularly the JNK and ERK1/2 signaling. Our study demonstrated that the implant surface nanostructure has great potential to trigger the host inflammatory response through distinct pathways from conventional biochemical factors, which may remind us to re-consider the unique regulation mechanisms of nano surface on cell functions. Our finding offers a theoretical basis for titanium implant modification to benefit tissue integration.


Quantitative Evaluation of Exon Skipping in Urine-Derived Cells for Duchenne Muscular Dystrophy.
Antisense oligonucleotide (ASO)-based exon skipping therapy is thought to be promising for Duchenne muscular dystrophy (DMD). For the screening or assessing patient eligibility before administering ASO to patients, in vitro testing using myoblasts derived from each DMD patient is considered crucial. We previously reported state-of-the-art technology to obtain patient primary myoblasts from MYOD1-induced urine-derived cells (UDCs) as a model of DMD. We hypothesize that the myoblasts may potentially reflect specific pathological phenotypes, leading to a path for precision medicine in DMD patients. Here, we describe a detailed protocol for both acquiring MYOD1-induced myoblasts from UDCs and evaluating the correction of DMD mRNA and protein levels after exon-skipping in the cells.


Human biomonitoring reference values, exposure distribution, and characteristics of metals in the general population of Taiwan: Taiwan environmental survey for Toxicants (TESTs), 2013-2016.
Human biomonitoring (HBM) provides information to identify chemicals that need to be assessed regarding potential health risks to human populations. We established a population-representative sample in Taiwan, namely the Taiwan Environmental Survey for Toxicants (TESTs) in 2013-2016. In total, 1871 participants (aged 7-97 years) were recruited from throughout Taiwan. A questionnaire survey was applied to obtain individuals' demographic characteristics, and urine samples were obtained to assess metal concentrations. Inductively coupled plasma-mass spectrometry was used to determine concentrations of urinary As (total), Cd, Co, Cr, Cu, Fe, Ga, In, Mn, Ni, Pb, Se, Sr, Tl, and Zn. The purpose of this study was to establish the human urinary reference levels (RVs) for metals in the general population of Taiwan. We found that median concentrations of urinary Cu, Fe, Pb, and Zn in males were statistically significant (p < 0.05) higher than in females (Cu: 11.48 vs. 10.00 μg/L; Fe: 11.48 vs. 10.46 μg/L; Pb: 0.87 vs. 0.76 μg/L; and Zn: 448.93 vs. 348.35 μg/L). On the contrary, Cd and Co were significantly lower in males than in females (Cd: 0.61 vs. 0.64 μg/L; and Co: 0.27 vs. 0.40 μg/L). Urinary Cd levels in the ≥18-year-old group (0.69 μg/L) were significantly higher than those in the 7-17-year-old group (0.49 μg/L, p < 0.001). Among the investigated metals, most were significantly higher in the 7-17-year-old group than in the ≥18-year-old group, except for Cd, Ga, and Pb. Participants who lived in central Taiwan had higher median levels of urinary Cd, Cu, Ga, Ni, and Zn than those in other regions. Median levels of urinary As, Cd, Pb, and Se were significantly higher in participants who lived in harbor (94.12 μg/L), suburban (0.68 μg/L), industrial (0.92 μg/L), and rural (50.29 μg/L) areas, respectively, than the others who lived in other areas. RV95 percentiles of urinary metals (ng/mL) for 7-17/≥18-year-old groups were As (346.9/370.0), Cd (1.41/2.21), Co (2.30/1.73), Cr (0.88/0.88), Cu (28.02/22.78), Fe (42.27/42.36), Ga (0.13/0.12), In (0.05/0.04), Mn (3.83/2.91), Ni (8.09/6.17), Pb (8.09/5.75), Se (122.4/101.9), Sr (556.5/451.3), Tl (0.57/0.49), and Zn (1314.6/1058.8). In this study, we have highlighted the importance of As, Cd, Pb, and Mn exposure in the general population of Taiwan. The established RV95 of urinary metals in Taiwanese would be fundamental information to promote the reduction of metal exposure or policy intervention. We concluded that urinary levels of exposure to certain metals in the general Taiwanese population varied by sex, age, region, and urbanization level. References of metal exposure in Taiwan were established in the current study.


Elapid alpha-toxins have no effect on the cholinergic responses of bivalve myocardia.
Elapid alpha-toxins (alpha-bungarotoxin, alpha-cobratoxin and crude Bungarus caeruleus venom) do not affect the myocardial nicotinic ACh receptors of the following bivalve molluscs: Mercenaria mercenaria, Chione cancellata, Mya arenaria, Mytilus edulis, Rangia cuneata and Crassostrea virginica.


The generation and propagation of the human alpha rhythm.
The alpha rhythm is the longest-studied brain oscillation and has been theorized to play a key role in cognition. Still, its physiology is poorly understood. In this study, we used microelectrodes and macroelectrodes in surgical epilepsy patients to measure the intracortical and thalamic generators of the alpha rhythm during quiet wakefulness. We first found that alpha in both visual and somatosensory cortex propagates from higher-order to lower-order areas. In posterior cortex, alpha propagates from higher-order anterosuperior areas toward the occipital pole, whereas alpha in somatosensory cortex propagates from associative regions toward primary cortex. Several analyses suggest that this cortical alpha leads pulvinar alpha, complicating prevailing theories of a thalamic pacemaker. Finally, alpha is dominated by currents and firing in supragranular cortical layers. Together, these results suggest that the alpha rhythm likely reflects short-range supragranular feedback, which propagates from higher- to lower-order cortex and cortex to thalamus. These physiological insights suggest how alpha could mediate feedback throughout the thalamocortical system.


A novel method to directionally stabilize enzymes together with redox mediators by electrodeposition.
This paper depicts a novel method to directionally stabilize enzymes together with redox mediators by electrodeposition. Chitosan was used as a stabilizing matrix. By electrochemical removal of local H(+), chitosan close to working electrode became locally insoluble, and enzymes and redox mediators in chitosan were stabilized. The microelectrode on home-made microelectrode array (MEA) served as the working electrode. Three model enzymes--horseradish peroxidase (HRP), glucose oxidase (GOD), and glutamate oxidase (GlOD)--were used to fabricate different biosensors, and the redox mediator model was a poly(vinylpyridine) complex of Os(bpy)2Cl and a diepoxide (PVP-Os). Biosensors fabricated by the method exhibited very high performance. For HRP biosensor fabricated by this method, the sensitivity was 5.274 nA μM(-1) mm(-2), with linear detection range (LDR) of 2-220 μM and limit of detection (LOD) of 1 μM (S/N=3); for GOD biosensor, the sensitivity was 2.65 nA μM(-1) mm(-2), with LDR of 4-500 μM and LOD of 2 μM (S/N=3); for GlOD biosensor, the sensitivity was 0.33 nA μM(-1)mm(-2), with LDR of 4-500 μM and LOD of 2 μM (S/N=3). Since this method is very simple and especially suitable for directionally introducing enzymes and redox mediators onto microelectrode without contaminating other sites in the same microenvironment, it could be used for fabricating in vivo or in vitro 2nd generation biosensors in μm-scale, especially in neuroscience.


School principals coping with child sexual abuse in their schools.
Schools serve a central role in prevention, disclosure and intervention in cases of child sexual abuse (CSA). As school principals often face CSA cases in their daily work, they may hold the key to making social change on this front. However, research on principals' experiences of contending with CSA remains limited. The current study is part of a larger qualitative research project examining various Israeli educators' coping with CSA among their students in diverse cultural contexts. In this study, we specifically focused on principals. The research questions were: (1) What are the unique ways in which school principals cope with cases of CSA during their course of daily work? (2) Do their cultural contexts and cultural affiliations shape their coping, and if so, how? In-depth interviews were conducted with 25 principals from multiple cultural groups (secular, religious and ultra-Orthodox Jews, and Arab-Muslims), which were analyzed using a thematic approach. The findings indicated that principals demonstrate three types of coping strategies in response to encounters with CSA in the course of their work: they may act as "navigators" (exclusively responsible); "sharers" (rely on teamwork); or "balancers" (negotiating between cultural and legal demands). Furthermore, two contextual factors affected their construction of coping: ongoing professional experience in cases of CSA and personal experiences, including being a CSA survivor. This study highlights the importance of principals in identifying and leading interventions for CSA cases. It also raises the need for training to combine reflective, experience-based practice alongside evidence-informed practice.


Long-term reversal of diabetes by subcutaneous transplantation of pancreatic islet cells and adipose-derived stem cell sheet using surface-immobilized heparin and engineered collagen scaffold.
Esterified collagen (EC) can be functionalized with heparin to enhance islet graft stability. Growth factors secreted by human adipose-derived stem cells (hADSCs) can bind efficiently to EC-heparin (EC-Hep), which enhances revascularization and cell protection. We investigated the therapeutic potential of a combined heparin-esterified collagen-hADSC (HCA)-islet sheet to enhance islet engraftment. This study was designed to assess the efficiency of using EC-Hep as a scaffold for subcutaneous islet transplantation in diabetic athymic mice. After the hADSC-cocultured islets were seeded in the EC-Hep scaffold, islet function was measured by glucose-stimulated insulin secretion test and growth factors in the culture supernatants were detected by protein array. Islet transplantation was performed in mice, and graft function and survival were monitored by measuring the blood glucose levels. β-Cell mass and vascular densities were assessed by immunohistochemistry. The EC-Hep composite allowed sustained release of growth factors. Secretion of growth factors and islet functionality in the HCA-islet sheet were significantly increased compared with the control groups of islets alone or combined with native collagen. In vivo, stable long-term glucose control by the graft was achieved after subcutaneous transplantation of HCA-islet sheet due to enhanced capillary network formation around the sheet. The findings indicate the potential of the HCA-islet sheet to enhance islet revascularization and engraftment in a hADSC dose-dependent manner, following clinical islet transplantation for the treatment of diabetes mellitus.


Resilience of Fungal Communities to Elevated CO2.
Soil filamentous fungi play a prominent role in regulating ecosystem functioning in terrestrial ecosystems. This necessitates understanding their responses to climate change drivers in order to predict how nutrient cycling and ecosystem services will be influenced in the future. Here, we provide a quantitative synthesis of ten studies on soil fungal community responses to elevated CO2. Many of these studies reported contradictory diversity responses. We identify the duration of the study as an influential parameter that determines the outcome of experimentation. Our analysis reconciles the existing globally distributed experiments on fungal community responses to elevated CO2 and provides a framework for comparing results of future CO2 enrichment studies.


Prognostic value of right ventricular free wall strain in pulmonary hypertension patients with pseudo-normalized tricuspid annular plane systolic excursion values.
Pulmonary hypertension (PH) is a progressively fatal disease having a significant impact on right ventricular (RV) function, a major determinant of long-term outcome in PH patients. In our clinic we frequently noticed the combination of PH and reduced RV function, but with discordant Tricuspid Annular Plane Systolic Excursion (TAPSE) values. The present study focuses on whether RV free wall strain measured using 2-dimensional speckle-tracking echocardiography is able to predict mortality in this subgroup of PH patients. 57 patients with PH and RV dysfunction (visual echocardiographic assessment of ≥2) and pseudo-normalized TAPSE values (defined as ≥16 mm) were retrospectively evaluated. Patients were divided by RV free -20 % as cut-off value. Follow-up data on all-cause mortality were registered after a median follow-up time of 27.9 ± 1.7 months. RV free of ≥-20 % was predictive of all-cause mortality after a median follow-up time of 27.9 ± 1.7 months (HR 3.76, 95 % CI 1.02-13.92, p = 0.05). RV free ≥-20 % remained a significant predictor of all-cause mortality (HR 4.30, 95 % CI 1.11-16.61, p = 0.04) after adjusting for PH-specific treatment. On the contrary, TAPSE was not a significant predictor of all-cause mortality. RV free wall strain provides prognostic information in patients with PH and RV dysfunction, but with normal TAPSE values. Future studies with larger cohorts, longer follow-up periods and inclusion of more echocardiographic parameters measuring LV and RV function could confirm the strength of RV free ≥-20 % as a predictor of mortality for this subgroup of patients with PH.


Myoma-associated pain frequency and intensity: a retrospective evaluation of 1548 myoma patients.
To analyze the possible relation between symptoms (especially pain) reported by myoma patients and objective features of their myomas as determined by ultrasound. Specifically: (1) What is the frequency and intensity of myoma-related pain? (2) Does the pain intensity depend on the number, size, or location of the myomas? (3) Is there any correlation between premenstrual pain, menstrual pain, and pain during sexual intercourse? A retrospective analysis of data from a patient questionnaire and ultrasound exams, collected from February 2009 until January 2013 at the myoma clinic of a university hospital in a large European city. The study analyzed data from 1548 myoma patients. Patients completed a 0-10 Likert scale questionnaire about their symptoms. The number, size, and location of myomas were determined from ultrasound exams. The three most frequent symptoms reported were hypermenorrhea, dysmenorrhea, and premenstrual pain. There was no statistically significant relationship between premenstrual pain or pain during sexual intercourse on the one hand and the number, size, or location of myomas on the other hand. For women with severe dysmenorrhea (Likert-scale scores of 8-10), submucosal myomas were significantly more frequent than all other myoma locations (p=0.01). Severe dysmenorrhea (Likert-scale scores of 8-10) was reported by a significantly (p<0.001) greater portion of the women whose largest myoma had a largest diameter of <5cm than by the women whose largest myoma had a diameter ≥5cm. The number of myomas did not have a significant influence on the dysmenorrhea intensity. The three types of pain (premenstrual, menstrual, and/or during sexual intercourse) had moderate pairwise correlations (ρ values from 0.304 to 0.542) that were all statistically highly significant (p<0.001). Myoma-associated pain is, alongside hypermenorrhea, the most frequent problem reported by the affected patients. Unlike premenstrual pain and pain during sexual intercourse, the intensity of menstrual pain is clearly dependent on the location and size of the largest myoma. Further research is needed to better understand the degree to which the pain reported by the patients is due to features of the myomas versus other possible factors.


Population data for 15 loci (Identifiler Kit) in a sample from the Valley of Mexico.
We analyzed 242 individuals from the Valley of Mexico, including the larger and more cosmopolitan city of this country. They were PCR-typed for 15 STR loci with the AmpFlSTR Identifiler PCR Amplification Kit (Applied Biosystems). Allele frequencies for each STR were estimated and compared to previous reports. Genotype distribution by locus and by two-loci combination was in agreement with Hardy-Weinberg expectations for all fifteen STRs. This STR system in Mexican-mestizos presented a combined probability of exclusion (PE) and discrimination (PD) longer than 99.999%, respectively.


[Rapid setting calcium phosphate cement for craniomaxillofacial surgery. 6 years experience].
Long-term results using hydroxyapatite cement (Bone Source) for the reconstruction of the facial skeleton and the forehead are reported. The cement consists of 73% tetracalcium phosphate and 27% dicalcium phosphate. Using 0.25 M phosphoric acid instead of water, the primary setting time can be shortened from 20 to 5 min in an isothermic reaction. Twenty-two patients suffering from consequences of trauma, tumor-like lesions, or neoplasm as well as dysmorphia were treated. Following implantation, the healing process proceeded in most cases without complications. Due to hematoma and seroma as well as infection, two implants were lost. Follow-up examinations could be performed in 19 of the 22 patients on a average 40 months after operation. Most patients had good clinical long-term results. X-ray-analysis showed some discrete resorption of the implants in six patients. The further course must be decided based on clinical relevance. The hydroxyapatite cement used in this study evidenced good intraoperative handling, an excellent histologically proved biocompatibility, and good long-term stability in normal body fluid. Up to now we have limited its use to non-load-bearing applications in craniofacial surgery.


Synthesis of retinylphosphate mannose in yeast and its possible involvement in lipid-linked oligosaccharide formation.
A membrane fraction from Saccharomyces cerevisiae as well as a mannosyltransferase purified therefrom was shown to catalyze the transfer of mannose from GDPmannose to retinyl phosphate. The product formed has chromatographic and chemical properties characteristic for retinylphosphate mannose. The enzyme requires divalent cations. Mg2+ is more effective than Mn2+ with an optimum concentration around 25 mM. Amphomycin at a concentration of 0.1 mg/ml inhibits the reaction to 50%. Glycosyl transfer was specific for mannose residues from GDPmannose and did not occur with dolichylphosphate mannose nor with UDP galactose; UDPglucose is a poor donor. Formation of retinylphosphate mannose is inhibited by dolichyl phosphate. This observation as well as similarities between retinylphosphate mannose and dolichylphosphate mannose synthesis in respect to ion requirement, inhibition by amphomycin are suggestive that both reactions are catalyzed by one and the same enzyme. In experiments studying the glycosyl donor specificity in the assembly of lipid-linked oligosaccharide intermediates involved in N-glycosylation of proteins, it could be demonstrated that retinylphosphate mannose can replace dolichylphosphate mannose in the final steps of mannosylation.


Protection against collagen-induced arthritis by intramuscular gene therapy with an expression plasmid for the interleukin-1 receptor antagonist.
The interleukin-1 receptor antagonist (IL-1Ra) is an endogenous protein that can prevent the binding of IL-1 to its cell-surface receptors. Among a number of techniques for gene transfer in vivo, the direct injection of naked DNA into muscle is simple, inexpensive and safe. In this study, we evaluated the potential of intramuscular gene therapy with plasmid DNA containing the cDNA for IL-1Ra in the prevention of murine collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type II collagen. At 4 weeks after the initial immunization, expression plasmid for IL-1Ra was injected into four selected sites in the thigh and calf muscles of DBA/1 mice. Control mice received the same plasmid, but lacking the IL-1Ra coding sequence. Macroscopic analysis of paws for redness, swelling and deformities showed that the onset of moderate to severe CIA in the paws of mice injected with IL-1Ra DNA was significantly prevented (P<0.05). In addition, both the synovitis and the cartilage erosion in knee joints were dramatically reduced in mice treated with IL-1Ra DNA (P<0.05). The expression of IL-1beta was significantly decreased in the ankle joints of mice treated with IL-1Ra (P<0.01). Interestingly, the levels of IL-1Ra in sera and joints after intramuscular injection of IL-1Ra DNA were significantly lower than when protein had been used in previous reports, suggesting that the therapeutic effect may be achieved by an alternative mechanism(s) rather than by systemic elevation of IL-1Ra. These observations provide the first evidence that direct intramuscular injection of expression plasmid for IL-1Ra may effectively suppress the inflammatory pathology in arthritis.


CSF and plasma morphine concentrations in cancer patients during chronic epidural morphine therapy and its relation to pain relief.
Seventeen patients with advanced cancer pain, treated with chronic epidural morphine, were studied. Minimum plasma and CSF morphine concentrations (CSSmin) were determined at pharmacokinetic steady state. A linear relationship was found between epidural morphine dose and concentrations obtained in plasma (r = 0.92) as well as CSF (r = 0.90). The line for best fit was much steeper for CSF than for plasma. The CSF/plasma concentration gradient of morphine at CSSmin was 132 +/- 31 (mean +/- S.E.M.). Large interindividual variations of morphine concentrations in CSF were found. It is suggested that the variations are due to substantial differences in transdural morphine diffusion between individuals. No correlation was found between pain relief, evaluated with a visual analog scale, and CSF morphine concentrations at pharmacokinetic steady state, when calculated in 9 patients. Mean duration of treatment was 104 days (range 14-366) and the daily dose was increased from 18 +/- 2 to 87 +/- 31 mg/day (mean +/- S.E.M.). A total of 39 epidural catheters were inserted in 14 patients. The catheters were patent for 2-223 days with a mean of 38 days. When re-examined later during treatment, 2 out of 8 patients demonstrated decreased CSF morphine concentrations in spite of increased doses given. One patient with extremely high dose demand is reported on separately and data supporting the concept of a combined spinal and systemic brain morphine effect in such cases are presented. Side effects were not a major problem but the possibility of infectious complications should be considered during chronic epidural morphine therapy.


Enhancement of ε-poly-L-lysine production coupled with precursor L-lysine feeding in glucose-glycerol co-fermentation by Streptomyces sp. M-Z18.
ε-Poly-L-lysine (ε-PL), one of the only two homo-poly amino acids known in nature, is used as a preservative. In this study, strategies of feeding precursor L-lysine into 5 L laboratory scale fermenters, including optimization of L-lysine concentration and time, was investigated to optimize the production of ε-PL by Streptomyces sp. M-Z18. The optimized strategy was then used in ε-PL fed-batch fermentation in which glucose and glycerol served as mixed carbon sources. In this way, a novel ε-PL production strategy involving precursor L-lysine coupled with glucose-glycerol co-fermentation was developed. Under optimal conditions, ε-PL production reached 37.6 g/l, which was 6.2 % greater than in a previous study in which glucose and glycerol co-fermentation was performed without added L-lysine (35.14 g/l). To the best of our knowledge, this is the first report of the enhancement of ε-PL production through L-lysine feeding to evaluate the use of fermenters. Meanwhile, the role of L-lysine in the promotion of ε-PL production, participating ε-PL synthesis as a whole, was first determined using the L-[U-(13)C] lysine labeling method. It has been suggested that the bottleneck of ε-PL synthesis in Streptomyces sp. M-Z18 is in the biosynthesis of precursor L-lysine. The information obtained in the present work may facilitate strain improvement and efficient large-scale ε-PL production.


Study on cathepsin B activity in human thyroid tumors.
Cathepsin B activity was measured in human thyroid tissue obtained surgically from 2 patients with Grave's disease, 3 with follicular adenoma, 4 with papillary carcinoma, and 4 with follicular carcinoma. Three normal thyroid tissues were also studied. Comparisons were made between cathepsin B activity and clinical findings, including histopathological diagnosis and the presence or absence of extra-capsular invasion and metastasis. The abilities of original tumors to degrade type I and type IV collagen were also measured. Mean cathepsin B activities of both specimens with benign and those with malignant disease were significantly higher than those of normal thyroid. On cases of thyroid carcinoma, those with extra-capsular invasions and metastasis had the highest cathepsin B activities. Cases with high cathepsin B activities also tended to show high type I and IV collagen degrading abilities. These findings suggest that cathepsin B plays a role in the development of extra-capsular invasion and lymph node metastasis in human thyroid tumors.


Sequential testing for efficacy in clinical trials with non-transient effects.
This paper describes a new type of sequential testing for clinical trials. The sequential nature of the data is not from additional patients, but rather from longer follow-up times. At each analysis, the null hypothesis that all treatments are equivalent in effect on the outcome after that amount of time is tested. The trial might still have staggered entry or not, but the key feature is that a different statistical hypothesis is tested at each analysis. It is assumed that any effect of treatment is non-transient, allowing a conclusion to be drawn in favour of one treatment or the other based on a difference at a single follow-up time. It is shown that a general method based on the Bonferroni inequality can be used to obtain critical cutpoints for sequential testing, that controls the chance of a type I error for the clinical decision. This method is applicable regardless of the test used at each analysis. In the case of a two-armed trial with a Gaussian outcome variable, it is shown how simulation can be used to obtain critical cutpoints that maintain the chance of a type I error for the clinical decision. The methods are compared by Monte-Carlo simulation, and it is seen that in most practical cases the Bonferroni method is not very conservative. The Bonferroni procedure is illustrated on the results of a real clinical trial of Pirfenidone on pulmonary fibrosis in Hermansky-Pudlak Syndrome.


Trends in Degradable Mesoporous Organosilica-Based Nanomaterials for Controlling Drug Delivery: A Mini Review.
The last few years of enhancing the design of hybrid mesoporous organosilica nanoparticleshas allowed their degradation under specific pathologic conditions, which finally is showing a lightin their potential use as drug delivery systems towards clinical trials. Nevertheless, the issueof controlling the degradation on-demand at cellular level still remains a major challenge, even if ithas lately been addressed through the incorporation of degradable organo-bridged alkoxysilanesinto the silica framework. On this basis, this mini review covers some of the most recent examplesof dierent degradable organosilica nanomaterials with potential application in nanomedicine,from degradable non-porous to mesoporous organosilica nanoparticles (MONs), functionalized withresponsive molecular gates, and also the very promising degradable periodic mesoporous organosilicamaterials (PMOs) only consisting of organosilica bridges.


Highly tunable arylated cinchona alkaloids as bifunctional catalysts.
We report the design and evaluation of a library of chiral bifunctional organocatalysts in which the distance between the catalytically active units can be systematically varied.


Distinct structural elements dictate the specificity of the type III pentaketide synthase from Neurospora crassa.
The fungal type III polyketide synthase 2'-oxoalkylresorcylic acid synthase (ORAS) primes with a range of acyl-Coenzyme A thioesters (C4-C20) and extends using malonyl-Coenzyme A to produce pyrones, resorcinols, and resorcylic acids. To gain insight into this unusual substrate specificity and product profile, we have determined the crystal structures of ORAS to 1.75 A resolution, the Phe-252-->Gly site-directed mutant to 2.1 A resolution, and a binary complex of ORAS with eicosanoic acid to 2.0 A resolution. The structures reveal a distinct rearrangement of structural elements near the active site that allows accommodation of long-chain fatty acid esters and a reorientation of the gating mechanism that controls cyclization and polyketide chain length. The roles of these structural elements are further elucidated by characterization of various structure-based site-directed variants. These studies establish an unexpected plasticity to the PKS fold, unanticipated from structural studies of other members of this enzyme family.


Bone radiomics reproducibility: a three-centered study on the impacts of image contrast, edge enhancement, and latitude variations.
This study aims to measure the reproducibility of radiomics features in ankle bone radiography over changes in post-processing parameters including contrast, edge enhancement and latitude. Lateral ankle bone radiographies for sixty patients were obtained from three digital radiology centers. All images were acquired by same image acquisition settings. A two-dimensional region of interest was drawn in any image and 93 features from 6 feature sets including first and second order were extracted. The coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated to assess feature reproducibility for each center and among all centers in three scenarios: Adams (Nat Rev Endocrinol 9(1):28, 2013) ten different contrast Brown et al. (J Med Imaging 5(1):011017, 2018) ten different edge enhancement and Hirvasniemi et al. (Osteoarthr Cartilage 27(6):906-914, 2019) ten different image latitude parameters. Based on ICC analysis, it is observed that 46-100-44% of Histogram, 54-72-42% of GLCM, 43-76-36% of GLDM, 60-90-17% of GLRLM, 33-19-21% of GLSZM and 13-20-0% of NGTDM radiomics features had 90% < ICC < 100% over changes in contrast-edge enhancement-latitude changes respectively. Based on COV, GLRLM was only feature set that 100% of their features had COV ≤ 5% over changes in contrast and edge enhancement. The results presented here, indicating that radiomics features extracted are vulnerable over changes in contrast, edge enhancement and latitude. The most reproducible features that introduced in this study could be used for further clinical decision making.


The feasibility of demonstration of GM- and InV-systems in decaying organs.
Gamma-globulin factors (Gm and InV-systems) were determined in 12 cadavers in blood and various organ exprimates (kidney, liver, spleen and muscle). Also checked was the time interval up to which these factors could still be demonstrated in decaying organs. For this purpose blood and portions of the organs were left to decay in plastic containers at an average temperature of 19.1 degree C. Examinations were done with the agglutination-inhibition-test. The exprimates were employed in dilutions 1:10 and 1:20. The serum factors Gm (1), (2), (4), (10) and InV (1) could be demonstrated for varying periods of time. In organs they could be demonstrated for between one and eight weeks. Only factors Gm(1) and Gm(2) could be demonstrated beyond this time. As a rule these serum factors were demonstrable in blood for a longer period of time than in organs; Factor Gm(4) proved to be the most stable one, as it could be demonstrated up to 11 weeks in decaying serum. In 2200 individuals tests with a dilution 1:20 no false positive results were obtained, with the dilution 1:10, however, 5 false positive tests were found. No explanation can be given for the different periods of time for which these factors can be demonstrated under conditions of decay.


Taurine effect on neuritic outgrowth from goldfish retinal explants in the absence and presence of fetal calf serum.
Post-crush goldfish retinal explants were cultured in the absence of fetal calf serum and in the presence of calcium, albumin, glucose or taurine. There was an increase in length and density of the neurites in a dose-dependent manner when fetal calf serum was added to the medium. The addition of calcium to the basic medium, Leibovitz, produced a small increase in neuritic outgrowth at low concentrations, but inhibited outgrowth at higher levels. Albumin did not significantly modify neuritic outgrowth. Glucose, at variable concentrations, produced a bell-shaped increase in length and density of the neurites. Taurine, in the absence of fetal calf serum, produced a small increase in neuritic outgrowth at 10 mM. In the presence of glucose, taurine stimulated outgrowth was less efficient than in the presence of fetal calf serum. In order to investigate the mechanisms of action of taurine as a trophic agent, the culture medium in the absence of fetal calf serum will be supplemented with glucose.


Siwa Oasis groundwater quality: factors controlling spatial and temporal changes.
Siwa Oasis is of great historical, environmental, and scientific importance, as it contains unique archeological and geological features. Groundwater is the main source of freshwater in that oasis. The carbonate aquifer groundwater, used for irrigation, was sampled to evaluate factors controlling quality changes spatially and temporally by applying hydrochemical and statistical analyses. The salinity of the aquifer varied spatially from 1367 to 8645 mg/l based on one hydrogeological condition, with the highest TDS (> 5432.5 mg/l, 25% of samples) at the central part of the study area. Temporally, the salinity changed slightly from 3754.3 mg/l (in 2014) to 4222.4 mg/l (in 2020). The cession of illegal wells, pumping control, and excavation of formed salts have a noticeable impact on salinity (mediate the increase in salinity) and ions. However, about 61% of the studied samples can be considered unsuitable for irrigation owing to salinity and can harm plant yield. The heavy metals studied (Fe, Mn, Cu, Pb), except Cd, were within the permissible limit for irrigation water. Finally, it is proposed to construct desalination stations to enhance water quality for irrigation in the study area and set up many companies for salt extraction.


Oscillatory vapour shielding of liquid metal walls in nuclear fusion devices.
Providing an efficacious plasma facing surface between the extreme plasma heat exhaust and the structural materials of nuclear fusion devices is a major challenge on the road to electricity production by fusion power plants. The performance of solid plasma facing surfaces may become critically reduced over time due to progressing damage accumulation. Liquid metals, however, are now gaining interest in solving the challenge of extreme heat flux hitting the reactor walls. A key advantage of liquid metals is the use of vapour shielding to reduce the plasma exhaust. Here we demonstrate that this phenomenon is oscillatory by nature. The dynamics of a Sn vapour cloud are investigated by exposing liquid Sn targets to H and He plasmas at heat fluxes greater than 5 MW m-2. The observations indicate the presence of a dynamic equilibrium between the plasma and liquid target ruled by recombinatory processes in the plasma, leading to an approximately stable surface temperature.Vapour shielding is one of the interesting mechanisms for reducing the heat load to plasma facing components in fusion reactors. Here the authors report on the observation of a dynamic equilibrium between the plasma and the divertor liquid Sn surface leading to an overall stable surface temperature.


Close ties, near and far away: patterns and predictors of geographic network range among older Europeans.
A growing number of older adults maintain connections in their core discussion networks at variant distances, raising concerns about the lack of discussants in proximity and the consequences on their social life. This study examines the typical geographic layouts for aging Europeans' core discussion networks and their implications for network function and quality. With a sample of community-dwelling respondents aged 50 and above from the Survey of Health, Aging, and Retirement in Europe, the present research identifies seven geographic layouts that extend previously identified family and diverse network types by adding spatial nuance. Individuals in mid-range and distant-family networks typically lack a discussant nearby but sustain high emotional closeness with family discussants at a distance and express high overall satisfaction with their network. Proximate-diverse networks with a strong representation of non-kin members nearby turn out to be less advantageous than prior research might suggest, providing relatively frequent contact but the lowest level of network satisfaction. Results also identify how individual characteristics link to the geographic layouts and describe their prevalence across European regions. Overall, relatively dispersed layouts are common for older adults across multiple countries and do not necessarily indicate lower emotional closeness and network satisfaction. The present study highlights the importance of looking beyond the mere presence of proximate connections in older adults' core networks.


Mobilization of iron from the plasma membrane of the murine reticulocyte. The role of ferritin.
1. Plasma membranes prepared by pre-incumbation of mouse reticulocytes with 125I, 59Fe-labeled murine transferrin were able to release 59Fe in preference to 125I when incubated in the presence of murine reticulocyte cytosol, demonstrating that the latter mobilized iron which had been dissociated from transferrin. 2. 59Fe in cytosol was associated with at least two components in addition to hemoglobin, a high molecular weight component, identified as ferritin by specific immunoprecipitation, and an as yet unidentified, low molecular weight component of approx 17 00. 3. Ferritin itself, in the absence of added cytosol, was abloe to mobilize 59Fe from s9Fe-labeled reticulocyte plasma membranes. 4. Lysates of reticulocytes synthesized 59Fe-labeled heme when incubated with 59Fe-labeled ferritin. 5. These findings reflect a pathway of iron uptake and incorporation into heme in which ferritin plays an active role.


Azobenzene-Containing Liquid Crystalline Twisted Ribbons via Polymerization-Induced Hierarchical Self-Assembly.
Polymerization-induced self-assembly incorporating liquid crystallization, as a polymerization-induced hierarchical self-assembly (PIHSA) method to produce polymeric particles with anisotropic morphologies facilely and efficiently, has drawn wide attention recently. However, the means of regulating the morphologies of liquid crystalline (LC) polymer assemblies still need to be explored. Herein, a route is presented to fabricate the twisted ribbons via PIHSA containing azobenzene based on poor reversible addition-fragmentation chain transfer (RAFT) control, called poorly controlled PIHSA. Cyano-4-(dodecylsulfanylthiocarbonyl)sulfanyl pentanoic acid-2-(2-pyridyldithio) ethyl ester is used as the RAFT agent with poor controllability, and the morphological evolution from ribbons to twisted ribbons can be observed in the corresponding PIHSA system. The formation mechanism of the twisted ribbons is studied systematically and the broad molecular weight distribution is considered to be the decisive factor. Moreover, the supramolecular chirality induced by symmetry breaking is also related to the twist of the ribbons. This study enriches the methods of controlling the morphologies of LC polymer particles and is helpful for further clarifying the mechanism of PIHSA.


Triple-negative breast cancers: unique clinical presentations and outcomes.
Triple-negative (TN) breast cancers lack estrogen receptor (ER), progesterone receptor (PR), and HER2/neu amplification (HER2). Few studies have been dedicated to characterizing this subset of cancer. Retrospective review of a prospectively collected database of patients treated for invasive breast cancer at a single institution. Three tumor marker groups were compared: TN [ER-/PR-/HER2-], HER2+ [ERx/PRx/HER2+], and ER+ [ER+/PRx/HER2-]. Over 8 years, 123 TN, 210 HER2+, and 728 ER+ patients were identified. On average, TN patients were younger (mean age TN 59.7, HER2+ 62.0, ER+ 64.5 years, P = 0.0001). They were referred for genetic testing more frequently (17% TN, 10% HER2+, 10% ER+, P = 0.055) and were most likely to have a BRCA mutation identified if tested (24% TN, 10% HER2+, 4% ER+, P = 0.019). TN tumors were larger (mean size 2.1 cm TN, 2.0 cm HER2+, 1.8 cm ER+, P = 0.031) and most commonly detected by breast exam (54% TN, 43% HER2+, 42% ER+, P = 0.025). Lymph node involvement was least common with TN tumors (21% TN, 37% HER2+, 32% ER+, P = 0.013), and angiolymphatic invasion was less common for TN than HER2+ (18% TN, 24% HER2+, 15% ER+, P = 0.006). TN patients had significantly higher local or regional recurrence (5.7% TN, 2.9% HER2+, 1.0% ER+, P = 0.001), and the worst 5-year overall survival, although this did not reach statistical significance (85% ± 6% TN, 94% ± 2% HER2+, 91% ± 2% ER+). TN breast cancers are associated with unique patient presentations, tumor characteristics, and clinical outcomes of which clinicians and investigators should be aware.


Soil particle size fractions affect arsenic (As) release and speciation: Insights into dissolved organic matter and functional genes.
Soil particle size fractions (PSFs) are important for arsenic (As) partitioning, migration, and speciation transformation. However, information is lacking about the environmental fate of As and its distribution on different PSFs. In the present study, two types of soils from mining areas were divided into four PSFs, including coarse sand (2-0.25 mm), fine sand (0.25-0.05 mm), silt (0.05-0.002 mm), and clay (< 0.002 mm) fractions. The results showed that As was enriched in the coarse sand, which was primarily affected by the content of organic carbon (OC), followed by iron (Fe), aluminum (Al), and manganese (Mn) (hydr)oxides. The elevated total As (TAs), As(III), organic As, Fe(II), and dissolved organic carbon (DOC) concentrations were mainly originated from the clay fraction. The intensified humification degree of DOM and promoted bacterial metabolism related to As/iron bioreduction were also exhibited in the clay fractions. The dynamics of As fractions in soils indicated the potential formation of secondary minerals and re-adsorption of As in the PSFs. The highest abundances of arrA, arsC, arsM, and Geo genes were found in the clay fraction, implying that the clay fraction potentially released more As, including As(III) and organic As. Results from the correlation analysis showed that elevated DOC concentrations promoted the catabolic responses of iron-reducing microorganisms and triggered microbial As detoxification. Overall, this study provides valuable information and guidance for the remediation of As-contaminated soils.


Serum amyloid A proteins reduce bone mass during mycobacterial infections.
Osteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. Genetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. We found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.


Abnormal tau in amyloid PET negative individuals.
We examined the characteristics of individuals with biomarker evidence of tauopathy but without β-amyloid (Aβ) (A-T+) in relation to individuals with (A+T+) and without (A-T-) evidence of Alzheimer's disease (AD). We included 561 participants with Aβ and tau PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We compared A-T- (n = 316), A-T+ (n = 63), and A+T+ (n = 182) individuals on demographics, amyloid, tau, hippocampal volumes, and cognition. A-T+ individuals were low on apolipoprotein E ɛ4 prevalence (17%) and had no evidence of subtly elevated brain Aβ within the negative range. The severity of tau deposition, hippocampal atrophy, and cognitive dysfunction in the A-T+ group was intermediate between A-T- and A+T+ (all p < 0.001). Tau uptake patterns in A-T+ individuals were heterogeneous, but approximately 29% showed tau deposition in the medial temporal lobe only, consistent with primary age-related tauopathy and an additional 32% showed a pattern consistent with AD. A-T+ individuals also share other features that are characteristic of AD such as cognitive impairment and neurodegeneration, but this group is heterogeneous and likely reflects more than one disorder.


Autonomic nervous system correlates to readiness state and negative outcome during visual discrimination tasks.
Decision-making in daily activities require different levels of mental load depending on both objective task requirements and self-perception of task constraints. Such factors elicit strain that could influence information processing, decision-making, and forthcoming performance. This experiment aimed at studying how task difficulty, errors and unfair feedback may impact strain. Participants were requested to compare two polygons and to decide as quickly and accurately as possible whether these were identical or different. Task difficulty depended upon the number of polygon sides (from 12 to 21 sides) and their degree of similarity (different by 1, 2 or 3 sides). Reaction time (RT) and response accuracy were the dependent variables as well as electrodermal activity (EDA) and Instantaneous Heart Rate (IHR). Physiological variables from the autonomic nervous system were expected to evolve as a function of strain. As expected, we found that RT increased along with task difficulty. Similarly, the amplitude of IHR responses was affected by task difficulty. We recorded bradycardia during the 5s pre-stimulation period associated with correct responses, while wrong responses were associated with tachycardia. Bradycardia was thus a predictive index of performance related to the readiness to act when the participants focused on external cues. Processing identical polygons elicited longer electrodermal responses than those for different polygons. Indeed, the comparison of two different polygons ended as early as the difference was found. When similar, the participants were still looking for a difference and the issue was uncertain until the performance was displayed. Unfair information, i.e. wrong feedback associated with a good response, as well as response errors elicited larger and longer electrodermal responses. Autonomic nervous system activity was thus task-specific, and correlated to both cognitive and emotional processes.


An investigation of the effect of silicone oil on polymer intraocular lenses by means of PALS, FT-IR and Raman spectroscopies.
The effect of the polydimethylsiloxane (PDMS) based silicone oil, that is widely used in vitreoretinal surgery, on internal structures of the polymer intraocular lenses was investigated. The effect of PDMS was studied on the polymethyl methacrylate (PMMA) rigid lenses and poly(2-hydroxyethyl methacrylate) (PHEMA) flexible lenses. The research was carried out by means of the positron lifetime spectroscopy (PALS) as well as the infrared spectroscopy (FT-IR) and the Raman spectroscopy (RS). The studies involving the use of PALS and FT-IR methods have revealed that the PHEMA based lenses absorbed, whereas the PMMA lenses did not absorb, silicone oil. The results obtained with the use of the RS method were inconclusive, probably due to the too low intensity of the characteristic PDMS bands. The evidence from this study was discussed in terms of physics and related to the clinical use of both silicone oil and intraocular lenses.


Silica nanoparticles induce ovarian granulosa cell apoptosis via activation of the PERK-ATF4-CHOP-ERO1α pathway-mediated IP3R1-dependent calcium mobilization.
Ambient particulate matters (PMs) have adverse effects in human and animal female reproductive health. Silica nanoparticles (SNPs), as a major component of PMs, can induce follicular atresia via the promotion of ovarian granulosa cell apoptosis. However, the molecular mechanisms of apoptosis induced by SNPs are not very clear. This work focuses on revealing the mechanisms of ER stress on SNP-induced apoptosis. Our results showed that spherical Stöber SNPs (110 nm, 25.0 mg/kg b.w.) induced follicular atresia via the promotion of granulosa cell apoptosis by intratracheal instillation in vivo; meanwhile, SNPs decreased the viability and increase apoptosis in granulosa cells in vitro. SNPs were taken up and accumulated in the vesicles of granulosa cells. Additionally, our results found that SNPs increased calcium ion (Ca2+) concentration in granulosa cell cytoplasm. Furthermore, SNPs activated ER stress via an increase in the PERK and ATF6 pathway-related protein levels and IP3R1-dependent calcium mobilization via an increase in IP3R1 level. In addition, 4-PBA restored IP3R1-dependent calcium mobilization and decreased apoptosis via the inhibition of ER stress. The ATF4-C/EBP homologous protein (CHOP)-ER oxidoreductase 1 alpha (ERO1α) pathway regulated SNP-induced IP3R1-dependent calcium mobilization and cell apoptosis via ATF4, CHOP, and ERO1α depletion in ovarian granulosa cells. Herein, we demonstrate that ER stress cooperated in SNP-induced ovarian toxicity via activation of IP3R1-mediated calcium mobilization, leading to apoptosis, in which the PERK-ATF4-CHOP-ERO1α pathway plays an essential role in ovarian granulosa cells.


Detection of Babesia bigemina in cattle by a radioimmunoassay incorporating specifically depleted antigen.
It was observed that mild acidification (pH less than 4.0) together with solvent extraction of the soluble sonicate of a crude preparation of Babesia bigemina infected cattle erythrocytes caused a quantitative loss of B. bigemina-specific antigen. Cross-reacting antigen activities with Babesia bovis remained intact. These properties were utilized in an assay system wherein antibody response to the specifically depleted antigen preparation was subtracted from the response to the initial crude preparation leaving the net B. bigemina response. The radioimmunoassay based on this antigen system was verified using sera from known negative cattle and from cattle previously infected with B. bigemina, B. bovis or Anaplasma marginale. The following discrimination values were obtained: B. bigemina-positive sera less than 2% false negatives; negative sera, 2% false positives; B. bovis-positive sera, 4% false positives; A. marginale-positive sera, 0% false positives. Levels of cross-reactivity in the false positive results were in the "suspect" rather than positive class and in the case of B. bovis-positive sera, may have been due to non-specific antibodies induced by blood inoculation. In animals naturally infected with B. bovis only, there were no false positive reactions. B. bigemina antibodies were readily detectable in field sera for at least 10 months post-infection following infection by the cattle tick Boophilus microplus. This assay overcomes the problems of currently used tests for B. bigemina infection as it is both sensitive and specific and is able to discriminate between both field and laboratory infections of B. bigemina and B. bovis.


Colorectal cancer progression correlates with upregulation of S100A11 expression in tumor tissues.
Early detection and treatment of human colorectal cancers remain a challenge. Identification of new potential markers may help in the diagnosis of colorectal cancer. By comparative two-dimensional gel electrophoresis using extracts from colorectal tumor and adjacent normal tissues, we identified a calcium-binding protein, S100A11, which was highly expressed in colorectal cancer compared with adjacent normal tissues. We expanded our study in 89 clinical colorectal tumor samples to validate this finding and correlates S100A11 expression in human colorectal cancer tissues with various stages of the tumor by Western blotting and immunohistochemical staining. We identified a calcium-binding protein, S100A11, which was highly expressed in colorectal cancer compared with adjacent normal tissues. S100A protein was expressed predominantly in the cytoplasm of normal tissue; however, it was expressed in both the nuclei and cytoplasm of colorectal cancer. S100A11 level in colorectal cancer tissue was increased following stage progression of the disease. These findings suggest S100A11 could be helpful in the pathological study of colorectal cancer, especially for the classification of different stages in colorectal cancer.


The renin-angiotensin and adrenergic nervous system in cardiac hypertrophy in fructose-fed rats.
Hyperinsulinemia and insulin resistance are associated with left ventricular hypertrophy (LVH) and cardiovascular complications in hypertensive subjects. The aim of this study was to explore the mechanisms for LVH including activation of the renin-angiotensin system system (RAS) and the sympathetic nervous system and their activation by insulin using a rat model of hyperinsulinemia and insulin resistance. Male Sprague-Dawley rats were fed a high-fructose or control diet. The fructose-fed rats (FFR) were divided into four subgroups that were administrated either vehicle or the following antihypertensive drugs (n = 6-8) for 4 weeks: 1) olmesartan, an angiotensin II type 1 (AT1) receptor antagonist; 2) bunazosin, an alpha1-receptor blocker; and 3) hydralazine, a direct vasodilator. Fructose feeding induced significant increases in mean systolic blood pressure (BP) levels at 4 weeks (control, 117 v fructose, 131 mm Hg), left ventricular weight, and the sum of the insulin level in response to a glucose tolerance test (2 g/kg). Fructose feeding also increased urinary excretion of epinephrine and norepinephrine, the density of cardiac alpha1-adrenergic receptors, and the content of angiotensin II in the left ventricle. All antihypertensive drugs decreased systolic BP, but only the AT1 receptor antagonist attenuated the development of LVH in FFR. The AT1 receptor antagonist did not affect glucose-mediated insulin responses, but did suppress urinary catecholamine excretion and cardiac alpha1-adrenergic receptor density. Left ventricular hypertrophy in FFR may be less dependent on systemic elevations of BP and more dependent on the RAS and the sympathetic nervous system. Use of an AT1 receptor antagonist might be the most beneficial way to prevent progression of LVH through direct effects on tissue RAS and the sympathetic nervous system in FFR. As these changes occur in a rat model with hyperinsulinemia, insulin may have a role in promoting LVH by activating the local RAS and sympathetic nervous system activity.


Methodologies for assessing exposure to metals: speciation, bioavailability of metals, and ecological host factors.
Host factors play a role in the bioavailability of metals, making it critical to understand their nature and how to measure them, as well as how to measure bioavailability with respect to host factors. The host factors that are critical to consider during all phases of bioavailability studies are age, gender, size, genetic characteristics, behavior (food chain considerations), and interactions between all of them. Some of these vulnerabilities are unique to individuals, populations, species, or communities. There are many interactions between and among metals, the species of metals, and the physical environment (pH, salinity). Some factors enhance uptake and absorption, whereas others moderate it. Moreover, some metals have greater effects on invertebrate organisms, whereas other metals (or species thereof) affect vertebrates more strongly. Fish and wildlife are useful as sentinel species and bioindicators because they can help us understand the risk to the organisms themselves, to the ecosystem, and to humans.


Synthesis of New Five Coordinated Copper(II) and Nickel(II) Complexes of L-Valine and Kinetic Study of Copper(II) with Calf Thymus DNA.
Five coordinated novel complexes of CuII and NiII have been synthesized from benzil and 1,3- diaminopropane-CuII/NiII complex and characterized by elemental analysis, i.r., n.m.r., e.p.r, molar conductance and u.v-vis, spectroscopy. The complexes are ionic in nature and exhibit pentaeoordinated geometry around the metal ion. The reaction kinetics of C25H36N5O2CuCl with calf thymus DNA was studied by u.v-vis, spectroscopy in aqueous medium. The complex after interaction with calf thymus DNA shows shift in the absorption spectrum and hypochromicity indicating an intercalative binding mode. The Kobs values have been calculated under pseudo-first order conditions. The redox behaviour of complex C25H36N5O2CuCl in the presence and in the absence of calf thymus DNA in the aqueous solution has been investigated by cyclic voltammetry. The cyclic voitammogram exhibits one quasi-reversible redox wave corresponding to CuII/CuI redox couple with E1/2 values of -0.377 and -0.237 V respectively at a scan rate of 0.1Vs-1 .On interaction with calf thymus DNA, the complex C25H36N5O2CuCl exhibits shifts in both Ep as well as in E1/2 values, indicating strong binding of the complex to the calf thymus DNA.


Occlusal height difference between maxillary central and lateral incisors: should aesthetic perception influence bracket placement?
The aim of this study was to verify anecdotal evidence that the maxillary central-to-lateral occlusal height difference (OHD) of more than 0.5 mm is a feature displayed in the majority of media and to discuss its implications for individualized orthodontic treatment planning. Photographs of smiling female models were collected from a variety of printed advertisements and allocated to 3 groups (n = 30 each): 1 dental, 2 fashion and 3 orthodontics. Group 4 used female patient images from orthodontic textbooks, assuming an OHD of 0.5 mm between maxillary central and lateral incisors. OHD was assessed by measuring the incisor height on the photographs and using average values to establish height differences. The average maxillary central-to-lateral incisor OHD differences were 1.39 mm (dental literature), 1.34 mm (fashion advertisements), 1.23 mm (orthodontics) and 0.62 mm (orthodontic textbooks) respectively. The differences between the advertisement groups were not significant (P > 0.05), but for orthodontic textbooks they were (P < 0.001). Advertisers seem to prefer greater maxillary central-to-lateral OHD compared to commonly used bracket placement protocols. Therefore, discussing OHD at start of treatment is recommended; modification of commonly used bracket placement protocols may be helpful to achieve desired aesthetic outcome.


Biomaterial-Guided Recombinant Adeno-associated Virus Delivery from Poly(Sodium Styrene Sulfonate)-Grafted Poly(ɛ-Caprolactone) Films to Target Human Bone Marrow Aspirates.
Scaffold-guided gene transfer offers strong systems to develop noninvasive convenient therapeutic options for the treatment of articular cartilage defects, especially when targeting bone marrow aspirates from patients containing chondroregenerative mesenchymal stromal cells in a native microenvironment. In this study, we examined the feasibility of delivering reporter (red fluorescent protein [RFP], lacZ) recombinant adeno-associated virus (rAAV) vectors over time to such samples through biocompatible mechanically stable poly(ɛ-caprolactone) (PCL) films grafted with poly(sodium styrene sulfonate) (pNaSS) for improved biological responses as clinically adapted tools for cartilage repair. Effective transgene expression (RFP, lacZ) was noted over time in human bone marrow aspirates using pNaSS-grafted films (up to 90% efficiency for at least 21 days) versus control conditions (ungrafted films, absence of vector coating on the films, free or no vector treatment), without displaying cytotoxic nor detrimental effects on the osteochondrogenic or hypertrophic potential of the samples. These findings demonstrate the potential of directly modifying therapeutic bone marrow from patients by controlled delivery of rAAV using biomaterial-guided procedures as a future noninvasive strategy for clinical cartilage repair. Impact statement Injured articular cartilage does not fully regenerate on itself and none of the currently available clinical and experimental therapeutic procedures are capable of restoring an original hyaline cartilage in sites of injury. Biomaterial-guided gene delivery has a strong potential to enhance the processes of cartilage repair. The system presented here based on the FDA-approved biocompatible poly(ɛ-caprolactone) material provides a functional scaffold for the controlled delivery of clinically adapted recombinant adeno-associated virus vectors as an off-the-shelf compound that could be applicable in a minimally invasive manner in patients.


Homocysteine is related to aortic mineralization in patients with ischemic heart disease.
Homocysteine is implicated as an early atherosclerotic promoter, which enhances the smooth muscle cell proliferation and produces free radicals that induce cellular damage. These factors must have a role in the progression of atherosclerosis that subsequently leads to vascular mineralization. Identify a correlation between the plasma concentration of total homocysteine and the amount of minerals that accumulate in the aorta of patients with atherosclerosis. We performed a cross-sectional study in 13 patients with three-vessel coronary artery disease, undergoing coronary artery bypass surgery. Aortic and mammary artery specimens were analyzed using a scanning electron microscope with an energy dispersive X-ray spectrometer. The homocysteine was determined using an immunonephelometry method. The amount of minerals in the aorta was greater (300 ± 181.6 particles per 500 µm2 than that in the mammary artery (64 ± 45 particles per 500 µm2 (p < 0.01). The average tHcy was 9.5 ± 2.3 µmol/L. The Spearman's rank correlation coefficient was positive between tHcy, and aortic iron (p < 0.05). Our study demonstrates that the aorta is dramatically affected by mineralization compared to the mammary artery. In addition, a direct correlation was identified between the levels of tHcy and the iron particles in the aortic wall.


Newborn auditory follow-up.
Because hearing is a key component in the infant's development of speech, language, and cognition, early detection of infant hearing loss is critically important. The routine evaluation of hearing should include the identification of parental concerns regarding infant hearing as well as the assessment and diagnosis of infants with potential hearing impairment. Identification of hearing loss should be followed by early interventions to prevent developmental delays. This article promotes universal screening of newborn hearing. The article also provides a review of the embryogenesis of hearing and includes a breakdown of risks for hearing loss, recommendations for auditory testing, and suggestions for follow-up, early intervention, and support for families of infants with hearing impairment.


Neurocognitive deficits and personality traits among euthymic patients with mood disorders in late life.
Previous studies revealed that acute depressive episodes are associated with both cognitive deficits and modified personality patterns in late life. Whether or not these psychological changes are present after remission remains a matter of debate. To date, no study provided concomitant assessment of cognition and psychological functions in this particular clinical setting. Using a cross-sectional design, 58 remitted outpatients (36 with unipolar early-onset depression (EOD) and 22 with bipolar disorder (BD)) were compared to 62 healthy controls. Assessment included detailed neurocognitive measures and evaluation of the five factor personality dimensions (NEO-Personality Inventory). Group comparisons revealed significant slower processing speed, working and episodic memory performances in BD patients. EOD patients showed cognitive abilities comparable to those of elderly controls. In NEO PI assessment, both BD and EOD patients displayed higher Depressiveness facet scores. In addition, the EOD but not BD group had lower Extraversion factor, and Warmth and Positive Emotion facet scores than controls. After remission from acute affective symptoms, older BD patients show significant impairment in several cognitive functions while neuropsychological performances remained intact in elderly patients with EOD. Supporting a long-lasting psychological vulnerability, EOD patients are more prone to develop emotion-related personality trait changes than BD patients.


Effect of ploidy on spontaneous mutation rate to asparagine non-requirement in cultured cells.
Variations in ploidy do not affect the spontaneous mutation rate to asparagine non-requirement in Jensen rat sarcoma cells cultivated in vitro.


"I think taking herbal medicine first can help prevent. If it doesn't work, then can take start taking the medication given by the doctors." Patients' perceptions towards hypertension in Fiji.
Hypertension remains a public health challenge worldwide however, the prevention, detection, treatment and management of this condition are not highly prioritized. Health knowledge has an important impact on individual's health. The ability to actively participate in screening, diagnosis and management of hypertension are influenced by patient's knowledge of hypertension. To understand why hypertension is so difficult to control, it may be of benefit to gain an understanding of the patient's perspective. Hence, the aim of the study is to explore the perceptions of patients on prevention and diagnosis of hypertension in Fiji. The study used a qualitative method approach. The study was conducted at the four purposively selected health centers in the Lautoka/ Yasawa medical subdivision. A purposive sampling was used which included all the patients who attended the SOPD, age more than 18 years and above, diagnosed with hypertension for 6 months or more and attended clinic at one of the 4 selected health centers. Semi-structured open-ended interview guide were used to collect data among patients through in-depth interviews. Thematic analysis was used manually to analyze the data using four steps that is immersion in the data, coding the data, creating categories and identifying themes / subthemes. Twenty-five SOPD patients took part in the in-depth interview and the responses were grouped into two themes. The themes emerged included hypertension knowledge and diagnosis of hypertension in a closed family and self. Subthemes derived from the hypertension knowledge were measures of awareness, hypertension aetiology, risk perception, origin of information and concept of prevention. Sub themes derived from the diagnosis of hypertension in a closed family were perception when first diagnosed, hypertension in relation and hypertension impact. Patients' knowledge on etiologies and risk factors of hypertension were generally poor. Majority of the participants learnt about hypertension in hospitals and few over radios and television. Diagnosis in a closed family triggered worrisome, fear and fright on some patients. Majority of the patients have less knowledge about various risk factors of hypertension. Worrisome, fearful, frightful, frustration and sadness were some of the reactions and emotions highlighted by the patients. It is important to design culturally tailored interventions that address the psychological and behavioral needs of the patients. Recommendation to conduct further studies to understand the perception of hypertension among the general public.


Effect of quality characteristics of single sample preparation steps in the precision and coverage of proteomic studies--a review.
Proteomic profiling and biomarker search are analytical tools as many other. Nevertheless, in the proteomic discovery phase considerable sample fractionation is inevitable before readout. Since these procedures are of notable complexity, proteomic tools need in particular analytical quality validation standards as prevail for other analytical methods. With acceptance of the rule of error propagation the values of imprecision and yield of each preparation step determine overall reproducibility and therewith information harvest of a propagated method series. Thereto, we examined recent proteomic reports with reproducibility data and with parallelization, and automation approaches. Based on the data available from literature it is highly probable, that at least a part of current proteomic platforms actually suffer from high technical variance. The general need for quantification and the impact of precision and recovery levels with each step of typical multi-step workflows are illustrated. All sample preparation approaches that maximize yields (percent recoveries) and minimize overall imprecision should be suitable to improve reliability of biomarker search. This has to be realized by technical innovations that (a) minimize the imprecision of each serial sample preparation step, that (b) minimize the number of serial sample preparation steps, and that (c) parallelize all procedures with a maximum of automation.


"The students keep me hopeful": Teacher hope during the COVID-19 pandemic.
This study examined teacher enactment of hope, specifically willpower, waypower, and agency in the shadow of the COVID-19 glare. Participants of this mixed methods study were K-12 public school classroom teachers (n = 233) in a Western US state. Quantitative survey results indicated teachers maintained moderate to high levels of hope. Qualitative survey results indicated themes of obstacles that were unique to this pandemic context as well as indicators of willpower, waypower, and agency. This study illustrates teacher resiliency and the ways in which they shifted instruction under highly strenuous circumstances. Teachers maintained hope because of their dedication to the students.


Elastic and thermo-elastic characterizations of thin resin films using colored picosecond acoustics and spectroscopic ellipsometry.
Colored Picosecond Acoustics (CPA) and Spectroscopic Ellipsometry (SE) are combined to measure elastic and thermoelastic properties of polymer thin-film resins deposited on 300 mm wafers. Film thickness and refractive index are measured using SE. Sound velocity and thickness are measured using CPA from the refractive index. Comparing the two thicknesses allows checking consistency between both approaches. The same combination is then applied at various temperatures from 19° to 180°C. As the sample is heated, both thickness and sound velocity change. By monitoring these contributions separately, the Temperature Coefficient on sound Velocity (TCV) and the Coefficient on Thermal Expansion are deduced. The protocol is applied to five industrial samples made of different thin-film resins currently used by microelectronic industry. Young's modulus varies from resin to resin by up to 20%. TCV is large on each resin and varies from one resin to another up to 57%.


Dexamethasone stimulated gene expression in peripheral blood is a sensitive marker for glucocorticoid receptor resistance in depressed patients.
Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N=18 cases/18 controls) and a test cohort (N=11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes.


Collateral expression of proangiogenic and tumorigenic properties in intestinal epithelial cell variants selected for resistance to anoikis.
Although in vitro anchorage-independent growth is widely used as a marker of cell transformation, the biological implications of this trait are poorly understood. We previously demonstrated that enforced anchorage-independent growth of a nontumorigenic, immortalized epithelial cell line (IEC-18) in multicellular spheroid culture results in massive apoptotic cell death. This death process, termed anoikis, is prevented by expression of transforming oncogenes, which also confer tumorigenic competence. This study examines whether acquisition of an anoikis-resistant phenotype is causally related to the tumorigenic capacity of transformed epithelial cells. Parental IEC-18 cells were subjected to 10 cycles of selection for survival in speroid culture. Unlike parental cells, the resulting anoikis-resistant variants (AR1.10 and AR2.10) formed relatively large tumors in nude mice. Both anoikis-resistant sublines displayed upregulated expression of vascular endothelial growth factor (VEGF), a potent angiogenesis stimulator. VEGF121 overexpression alone did not induce tumorigenic conversion of parental IEC-18 cells, which remained highly susceptible to anoikis. We postulate that both anoikis-resistance and angiogenic-competence contribute to tumor formation. Development of anoikis-resistance can be then viewed as a precondition for expression of the tumorigenic phenotype. Our results suggest that even when angiogenesis is not a rate limiting factor (e.g. in vitro) the selective pressures of solid tumor-like, 3-dimensional growth conditions favoring anoikis resistance result in collateral induction of a proangiogenic phenotype.


"Synthesis, characterization and studies on antioxidant activity of silver nanoparticles using Elephantopus scaber leaf extract".
The simple, eco-friendly and cost effective method of green synthesis of silver nanoparticle in the leaf extract of medicinal plant Elephantopus scaber L. is illustrated in the present work. The synthesized silver nanoparticles (AgNPs) were characterized with UV-Vis-spectroscopy, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) analysis. The UV-spectra show maximum absorbance at 435 nm, NTA analysis shows 78 nm average sizes of nanoparticles, TEM analysis indicates spherical shape of the nanoparticles with the average diameter of 50 nm. The XRD peaks at 2θ range of 30-80° correspond to (111), (200), (220), (311) reflection planes that indicate the structure of metallic silver. FTIR analysis reveals surface capping of phenolic groups. Existence of peaks in the range of 1611 to 1400 cm(-1) indicates the presence of aromatic rings in the leaf extract. The peak at 1109 cm(-1) is due to the presence of OH groups. The antioxidant activity of synthesized nanoparticles was evaluated performing DPPH assay and it is observed that the photosynthesized nanoparticle also possesses antioxidant potentials. Thus, it can be used as potential free radical scavenger. Silver particles have tremendous applications in the field of diagnostics and therapeutics. To this context, the surface coating of plant metabolite constituents has great potentials. Therefore, the present work has been undertaken to synthesize the AgNPs using leaf extract of medicinal plant, E. scaber, to characterize and access their antioxidant properties.


Transcription analysis of class II human leukocyte antigen genes from normal and immunodeficient B lymphocytes, using polymerase chain reaction.
The RNA transcript levels of all human leukocyte antigen class II loci were determined from class II congenital immunodeficient B cells by polymerase chain reaction amplification of cDNA. No mRNA was observed under conditions in which 0.01% normal levels could be visualized. Pre-mRNA could be amplified from normal B cells but not from immunodeficient B cells, indicating a transcription defect.


Biocontrol of bacterial wilt in tomato with a cocktail of lytic bacteriophages.
Bacteriophages (phages) have been proposed as promising alternative pesticides against various bacterial diseases of crops. However, the efficacy of phages in managing plant bacterial diseases is variable and poorly understood in natural settings. In this study, two lytic phages, RpT1 and RpY2, were investigated for their biocontrol potential against bacterial wilt by Ralstonia pseudosolanacearum invasion in tomato plants. The two phages possess similar morphology and genome organization to those of the Autographiviridae family with a broad host range. Treatment with the two phages (alone or in combination) resulted in a significant reduction in bacterial wilt incidence. Three days post-treatment with phages, which was performed after R. pseudosolanacearum inoculation with a specified density of 108 PFU (plaque forming units)/g of soil, led to the most effective biocontrol activity compared to other treatments and a lower density of phage. A phage cocktail containing both RpT1 and RpY2 suppressed disease symptoms in agricultural soils, mimicking their ability to control diseases in natural settings. Furthermore, supplementation with specific adjuvants enhanced the biocontrol potential of both phages. The persistence of the two phages under various environmental conditions indicates their stable activity in soils. Consequently, the consistent biocontrol activity of these phages provides insights into the proper application, timing, and density of phages for effective phage therapy in bacterial wilt control in tomato. KEY POINTS: • Biocontrol potential of phages in natural settings individually and as a cocktail. • Apparent long-term persistence of phages in natural soils, various temperatures, and pH. • An effective approach for developing phages for biocontrol.


Lnc-Malat1 promotes slow myofiber-type transformation through sponging miR-129-5p in C2C12 myotubes.
Long non-coding metastasis-associated lung adenocarcinoma transcript (lnc-Malat1) emerges as a novel regulator in skeletal muscle development, while its function and the related mechanism is not fully revealed yet. In this study, knockdown of lnc-Malat1 by siRNA significantly inhibited the expression of myoblast marker genes (MyHC, MyoD, and MyoG) and slow muscle fiber marker genes (MyHC I), together with repressed expression of mitochondria-related genes COX5A, ACADM, CPTA1, FABP3, and NDUFA1. Overexpression of lnc-Malat1 exerted an opposite effect, promoting myoblast differentiation and slow muscle fiber formation. Dual luciferase reporter assay revealed a direct interaction between lnc-Malat1 and miR-129-5p, and overexpression of lnc-Malat1 significantly inhibited miR-129-5p expression, thereby elevating the expression of Mef2a, miR-129-5p target protein. In addition, enforced expression of lnc-Malat1 restored the inhibitory effect of miR-129-5p on myoblast differentiation and MyHC I expression. Taken together, our results suggest that lnc-Malat1 promotes myoblast differentiation, and maintains the slow muscle fiber phenotype via adsorbing miR-129-5p.


[Chinese material medica combined with cisplatin and lipiodol through transcatheter arterial embolization in the treatment of primary hepatoma].
Transcatheter arterial embolization (TAE) using hydroxycamptothecin, cantharidin and cisplatin which were mixed thoroughly with lipiodol, combined with large doses interferon and interleukin-2 as adoptive immunotherapy were carried out in the treatment of 48 patients with unresectable advanced stage primary hepatoma, evaluation of therapeutic effect showed that partial remission rate was 54.2%, significantly higher than that of embolization group using chemotherapeutic agents alone (cisplatin, adriamycin and mitomycin), the partial remission rate was 32.1% (P < 0.01). The side effects of camptothecin and cantharidin including hematuria, urodynia were also successfully eliminated.


Tigecycline.
New antimicrobial agents are urgently needed for clinical use due to the increasing prevalence and spread of multidrug-resistant bacteria that are commonly responsible for serious and life-threatening diseases. The need to develop new agents that effectively overcome existing mechanisms of resistance displayed by bacteria resistant to currently available drugs has become paramount. Tigecycline, the first in a new class of antimicrobials, the glycylcyclines, is an analogue of minocycline with additional properties that negate most mechanisms mediating resistance to the tetracyclines. In vitro testing has revealed that tigecycline has activity against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and many species of multidrug-resistant Gram-negative bacteria, although resistance to tigecycline by Pseudomonas aeruginosa and reduced susceptibility among Proteus species do occur. Tigecycline is being evaluated in multicentre Phase III clinical trials for therapy of many serious and life-threatening infections in which multidrug-resistant bacterial organisms may be found. Tigecycline appears to hold promise as a novel expanded spectrum antibiotic.


Risk factors associated with poor outcome after medial rectus resection for recurrent intermittent exotropia.
To describe characteristics of recurrent intermittent exotropia after bilateral lateral rectus (BLR) recession, and identify factors associated with poor outcome after unilateral medial rectus (MR) resection for recurrent intermittent exotropia. We retrospectively reviewed 124 patients who have undergone unilateral MR resection for recurrent intermittent exotropia after BLR recession. Patients were followed for at least 2 years after MR resection. Clinical characteristics and risk factors associated with poor outcome after unilateral MR resection were evaluated. Successful outcome was defined as distant deviation within the range of 4 prism diopters (PD) esotropia and 10 PD exotropia at last visit after MR resection. Among 124 patients, 50 patients (41.1%) were male, and the mean age at the time of MR resection was 9.5 ± 3.1 years. The average follow-up period after MR resection was 43.8 ± 23.7 months. Forty-seven patients (37.9%) were classified to have poor outcome at last visit, and 29 patients (23.4%) underwent third operation. None of the patients was overcorrected after MR resection. Multiple logistic regression analyses showed that distant deviation at post-operative 3 months and male gender were associated with poor outcome (OR 1.49; 95% CI 1.27-1.73; P < 0.001, and OR 5.19; 95% CI 1.42-18.98; P = 0.013, respectively). Ocular deviation at 3 months after unilateral MR resection for recurrent intermittent exotropia may play a valuable role in anticipating poor outcome. Patients whose exotropia exceeded 9 PD at distance at 3 months' follow-up tended to recur while those whose exotropia remained below 9 PD at distance showed a stable disease course.


GDF15 as a central mediator for integrated stress response and a promising therapeutic molecule for metabolic disorders and NASH.
Mitochondria is a key organelle for energy production and cellular adaptive response to intracellular and extracellular stresses. Mitochondrial stress can be evoked by various stimuli such as metabolic stressors or pathogen infection, which may lead to expression of 'mitokines' such as growth differentiation factor 15 (GDF15). This review summarizes the mechanism of GDF15 expression in response to organelle stress such as mitochondrial stress, and covers pathophysiological conditions or diseases that are associated with elevated GDF15 level. This review also illustrates the in vivo role of GDF15 expression in those stress conditions or diseases, and a potential of GDF15 as a therapeutic agent against metabolic disorders such as NASH. Mitochondrial unfolded protein response (UPRmt) is a critical process to recover from mitochondrial stress. UPRmt can induce expression of secretory proteins that can exert systemic effects (mitokines) as well as mitochondrial chaperons. GDF15 can have either protective or detrimental systemic effects in response to mitochondrial stresses, suggesting its role as a mitokine. Mounting evidence shows that GDF15 is also induced by stresses of organelles other than mitochondria such as endoplasmic reticulum (ER). GDF15 level is increased in serum or tissue of mice and human subjects with metabolic diseases such as obesity or NASH. GDF15 can modulate metabolic features of those diseases. GDF15 play a role as an integrated stress response (ISR) beyond mitochondrial stress response. GDF15 is involved in the pathogenesis of metabolic diseases such as NASH, and also could be a candidate for therapeutic agent against those diseases.


Toporosides A and B, Cyclopentenyl-Containing ω-Glycosylated Fatty Acid Amides, and Toporosides C and D from the Northwestern Pacific Marine Sponge Stelodoryx toporoki.
Toporosides A-D (1-4), new ω-glycosylated fatty acid amides, were isolated from the sponge Stelodoryx toporoki. The structures of these compounds, including absolute configurations of stereogenic centers, were established using analysis of 1D and 2D NMR, ECD, and HR mass spectra as well as chemical transformations. Toporosides A (1) and B (2) are the first lipids containing a cyclopentenyl α,β-unsaturated carbonyl moiety in the polymethylene chain. Toporoside C (3) is likely a precursor, which undergoes intramolecular aldol condensation to produce 1 and 2. Toporosides A, C, and D showed protective effects against TNF-α-induced injury in H9c2 cardiomyocytes.


Analysis of the characterization of NaOH-treated natural cellulose fibre extracted from banyan aerial roots.
Natural fibre is renewable and extensively utilized for structural and medicinal applications. The current research concentrates on surface modification for fibre enhancement using an alkaline treatment technique to extract raw fibre from banyan (Ficus benghalensis) aerial root bark. Using a 10% NaOH solution, attempts have been made to improve the crystalline, surface, thermal, physical, and chemical properties of banyan aerial root fibre (BAF). Five samples of BAF were produced by soaking the unprocessed fibre in an alkaline solution for variable amounts of time. On the surface of the treated BAF, a higher concentration of cellulose could be seen. The X-Ray Diffraction test revealed that the crystallinity index improved by 52%, with a crystalline dimension of 51.2 nm. It was observed that the crystalline content is increased in treated Banyan aerial root fiber due to this alkali treatment. The significance of natural fibre characterization is also briefly discussed, and this summary will serve as a resource for future studies on natural fibre composites by other researchers.


Contribution of sonographic measurement of ovarian volume to diagnosing ovarian tumors in postmenopausal women.
The purpose of this review article is to evaluate the current method of sonographic measurement of ovarian volume as a means of diagnosing ovarian tumors in postmenopausal women, in whom an ovarian volume greater than 10 ml is generally considered abnormal. After reviewing the general medical literature, we propose a nomogram of ovarian volume that may be used to determine whether an ovary is abnormal. Furthermore, on the basis of our previous results, we recommend that a cutoff point for ovarian volume that is adjusted to patient age be used to determine whether an ovary is abnormal. We recommend the use of such nomograms in routine clinical practice to assist physicians in identifying abnormality of the ovaries during sonographic examination.


Levels and health risks of carbonyl compounds in selected public places in Hangzhou, China.
The concentrations of six carbonyl compounds in indoor air were measured for selected public places in Hangzhou, including shopping centers, supermarkets, furniture store, inter-city bus stations, railway stations and cinemas. In indoor air of the public places, the mean concentration was 146.5 microg/m(3) for total carbonyls, in which formaldehyde was found to be the most abundant carbonyls with an average value of 90.6 microg/m(3) and followed by acetone and acetaldehyde. Among the selected public places, the furniture store presented the highest carbonyl concentrations in the indoor air, followed by shopping centers, supermarkets, cinemas, while the railway stations and inter-city bus stations presented relatively lower carbonyl concentrations. Carbonyl concentrations in indoor air for the different areas of shopping centers and supermarkets were also investigated. The results showed that the highest carbonyl concentrations were found in restaurant and bedclothes areas for shopping centers and in the cooked food areas for supermarkets. The average ratios of the indoor/outdoor (I/O) for carbonyl concentrations were greater than 1, which indicated that the indoor sources significantly contributed to carbonyls, such as indoor materials and anthropogenic activities. Preliminary estimate of the health risk for staffs, customers and passengers in public places was discussed.