Seasonal and interannual mobility of arsenic in a lake impacted by metal mining.
Detailed examination of the water column, sediments, and interstitial waters was conducted in Balmer Lake, Ontario, Canada, in 1993-1994 and 1999 in order to assess the seasonal and interannual controls governing the behavior of As. High-resolution profiles of dissolved (<0.45 microm) Fe, Mn, SO4(2-), and sigmaH2S across the sediment-water interface indicate the presence of reducing conditions in close proximity to the benthic boundary during ice-free periods, which are characterized by fully oxygenated bottom waters. Dissolved As is remobilized as As(III) in suboxic sediment horizons via the redox-controlled dissolution of Fe (and perhaps Mn) oxide phases. During 1993-1994, As fluxes to the water column were relatively low (2-15 microg cm(-2) year(-1)) and contributed between 2 and 18% of the water column inventory. Dissolved As in the lake waters was derived primarily from external mining-related loadings during this period. Between 1993 and 1999, external loadings of As to Balmer Lake decreased while [As]aq within the lake increased, suggesting an increase in the proportion of sediment-derived As. Indeed, benthic dissolved As fluxes in 1999 ranged from 179 to 380 microg cm(-2) year(-1), representing approximately 33-60% of the water column burden. The relatively recent importance of sedimentary arsenic sources is suggested to reflect changes to sediment redox conditions associated with a postulated increase in lake primary productivity. Ironically, the increased contribution of dissolved arsenic to the water column appears to have resulted from an otherwise improvement in water quality. Reduced loadings of Cu, Zn, and Ni to the lake since 1994 appear to have allowed increased phytoplankton production that has stimulated arsenic release.


Dilatory is a Drosophila protein related to AZI1 (CEP131) that is located at the ciliary base and required for cilium formation.
A significant number of ciliary disease genes have been found to encode proteins that localise to the basal body. By contrast, a large number of basal-body-associated proteins remain to be characterised. Here, we report the identification of a new basal body protein that is required for ciliogenesis in Drosophila. Dilatory (DILA) is a predicted coiled-coil protein homologous to vertebrate AZI1 (also known as CEP131). Mutations in dila specifically exhibit defects in ciliated cells (sensory neurons and sperm). Several features of the neuronal phenotype suggest a defect in intraflagellar transport. In sensory neuron cilia, DILA protein localises to the ciliary base, including the basal body and putative transition zone, and it interacts genetically with the ciliary coiled-coil protein, Uncoordinated. These data implicate DILA in regulating intraflagellar transport at the base of sensory cilia.


Atypical Paget's disease with quantitative assessment of tracer kinetics.
Paget's disease of bone is characterized by alterations in skeletal metabolism, affecting a single or multiple bones. Paget's is usually confined to an individual bone and typically does not spread or extend across joints. A patient with an unusual pattern of disease is presented together with quantitative assessment of the tracer kinetics pre- and posttreatment. A 75-year-old lady patient presented to her general practitioner in May 2002 with a history of lethargy. Clinical examination was unremarkable and further investigations such as blood tests (alkaline phosphatase levels), Tc-99m MDP bone scan, biopsy, and CT scan were carried out. Alkaline phosphatase levels were greater than 2000 IU/L (Normal: 31-116 IU/L). The Tc-99m MDP bone scan showed strikingly increased uptake in the central skeleton involving the thoracic vertebrae and the adjoining ribs. The bone biopsy was inconclusive. CT scan revealed symmetrical expansion of the ribs with bridging osteophytes across the ribs and spine. The patient was treated with risedronate and quantitative analysis of the pre- and posttherapy bone scans showed reduced plasma clearance in the pagetic bones. This case illustrates an unusual distribution of bone lesions in Paget's disease, which we think could be due to the result of degenerative disease leading to bridging and allowing direct extension of disease from one bone to another.


Fabrication of microcellular SiCN ceramics from templated polyvinylsilazane with expandable microspheres.
The microcellular SiCN ceramics with high porosity and high surface area were fabricated from polysilazane as a viscous SiCN ceramic precursor and expandable microspheres as a self-sacrificial template. The fabrication steps were composed of (1) forming of expandable microsphere compact, (2) infiltrating polysilazane into the compact, (3) foaming and curing, (4) pyrolysis in N2 gas. The microcellular structures and properties of the obtained ceramic products depended on the foaming and curing conditions as well as the pyrolysis temperature. When foamed and cured at 120 degrees C for 30 min, then pyrolyzed at 1000 degrees C in N2, the microcellular product exhibited the largest cell size 9.3 microm with the lowest cell densities 2.2 x 108 cells/cm2, 93% of porosity and surface area of 356 m2/g. Furthermore, the higher temperature pyrolysis at 1300 degrees C induced significant change in the microcellular morphology by reducing the cell size with thicker wall and the cell density. Finally, it demonstrated an efficient way of manufacturing highly porous microcellular ceramics with no etching process using a polyvinylsilazane and expandable microspheres for catalytic supporting application.


Is Exposure to Tobacco Advertising, Promotion and Sponsorship Associated with Initiation of Tobacco Use among Current Tobacco Users in Youth in India?
The rise in consumption of tobacco products among youth is a public health concern in India. Several studies have shown that advertisements promoting tobacco products influence decisions and behaviour of youth towards smoking. To ascertain which method of Tobacco Advertising, Promotion and Sponsorship (TAPS) was more influential for initiating tobacco use in youth in India. The secondary data of youth (15-24 years) from nationally representative Global Adult Tobacco Survey (GATS) conducted in 2009-2010 was analyzed. Odds ratio and p-value were used to know the association between TAPS and initiation of use of tobacco products among youth. Logistic regression was used to determine the most significant means of TAPS altering the youth's behaviour towards tobacco products. Out of 13,383 youths, 1,982 (14.7%) used smokeless forms of tobacco and 860 (6.38%) used smoke forms. Logistic regression reveals that promotional activities mainly through cinemas (p<0.05) and providing free samples of tobacco products (p<=.001) were most influential means of initiating consumption of tobacco products among youth. The smoking in youth is associated with watching advertisements particularly in cinema and promotional activities like distribution of free samples, coupons and sales on the price of tobacco products. Stronger legislative measures should be enforced to curb promotional advertisements in cinemas and distribution of free samples.


3D printed hybrid scaffolds for bone regeneration using calcium methoxyethoxide as a calcium source.
Introduction: Hybrids consist of inorganic and organic co-networks that are indistinguishable above the nanoscale, which can lead to unprecedented combinations of properties, such as high toughness and controlled degradation. Methods: We present 3D printed bioactive hybrid scaffolds for bone regeneration, produced by incorporating calcium into our "Bouncy Bioglass", using calcium methoxyethoxide (CME) as the calcium precursor. SiO2-CaOCME/PTHF/PCL-diCOOH hybrid "inks" for additive manufacturing (Direct Ink Writing) were optimised for synergy of mechanical properties and open interconnected pore channels. Results and Discussion: Adding calcium improved printability. Changing calcium content (5, 10, 20, 30, and 40 mol.%) of the SiO2-CaOCME/PTHF/PCL-diCOOH hybrids affected printability and mechanical properties of the lattice-like scaffolds. Hybrids containing 30 mol.% calcium in the inorganic network (70S30CCME-CL) printed with 500 µm channels and 100 µm strut size achieved the highest strength (0.90 ± 0.23 MPa) and modulus of toughness (0.22 ± 0.04 MPa). These values were higher than Ca-free SiO2/PTHF/PCL-diCOOH hybrids (0.36 ± 0.14 MPa strength and 0.06 ± 0.01 MPa toughness modulus). Over a period of 90 days of immersion in simulated body fluid (SBF), the 70S30CCME-CL hybrids also kept a stable strain to failure (~30 %) and formed hydroxycarbonate apatite within three days. The extracts released by the 70S30CCME-CL hybrids in growth medium did not cause cytotoxic effects on human bone marrow stromal cells over 24 h of culture.


Long-read ChIA-PET for base-pair-resolution mapping of haplotype-specific chromatin interactions.
Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a robust method for capturing genome-wide chromatin interactions. Unlike other 3C-based methods, it includes a chromatin immunoprecipitation (ChIP) step that enriches for interactions mediated by specific target proteins. This unique feature allows ChIA-PET to provide the functional specificity and higher resolution needed to detect chromatin interactions, which chromosome conformation capture (3C)/Hi-C approaches have not achieved. The original ChIA-PET protocol generates short paired-end tags (2 × 20 base pairs (bp)) to detect two genomic loci that are far apart on linear chromosomes but are in spatial proximity in the folded genome. We have improved the original approach by developing long-read ChIA-PET, in which the length of the paired-end tags is increased (up to 2 × 250 bp). The longer PET reads not only improve the tag-mapping efficiency but also increase the probability of covering phased single-nucleotide polymorphisms (SNPs), which allows haplotype-specific chromatin interactions to be identified. Here, we provide the detailed protocol for long-read ChIA-PET that includes cell fixation and lysis, chromatin fragmentation by sonication, ChIP, proximity ligation with a bridge linker, Tn5 tagmentation, PCR amplification and high-throughput sequencing. For a well-trained molecular biologist, it typically takes 6 d from cell harvesting to the completion of library construction, up to a further 36 h for DNA sequencing and <20 h for processing of raw sequencing reads.


[Coupled type of parasystole and its diagnosis].
Fifty patients with arrhythmia of the extrasystole type were examined by means of functional tests (atropine and physical exertion). Parasystole was revealed in 40 and extrasystole in 10 patients. The diagnosis of arrhythmia was based on determining the relative value of the longest pre-ectopic interval (R--R1, P--P1) and the relative value of the preceding cardiac cycle (R--R, P--P) prior to and after the functional tests. Reduction of the relative value of the longest pre-ectopic interval or increase of this interval by less than 10 per cent in the test was observed in extrasystole, an increase of the relative value of this interval by more than 10 per cent was encountered in parasystole. In cases with bigeminal rhythm, reduction of the absolute value of the longest pre-ectopic interval in the tests was characteristic of extrasystole while its increase was characteristic of parasystole.


Rat kidney renin and cathepsin D: purification and comparison of properties.
Renin and cathepsin D were purified by seven-step procedures involving five steps common to both enzymes. These common five steps were extraction of freeze-dried kidney powder in 30% methoxyethanol-water, diethylaminoethyl-cellulose (DEAE-cellulose) batch absorption and elution, pepstatin-aminohexyl-Sepharose chromatography, Sephadex G-100 chromatography, and DEAE-cellulose chromatography. The renin component was purified further by passage through an anti-rat spleen cathepsin D immunoglobulin G-Sepharose (IgG-Sepharose) column followed by carboxymethyl-Sephadex (CM-Sepharose) chromatography which separated two renin components. Cathepsin D activity obtained by the fifth step was purified by passage through an anti-rat kidney renin IgG-Sepharose column followed by DEAE-Sephacel chromatography which separated three cathepsin D components. The homogeneity of renin and cathepsin D preparations was demonstrated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The two components of renins showed molecular weights of 42 000 and 36 000 by gel filtration and 38 000 and 36 000 by SDS gel electrophoresis, respectively. They showed isoelectric points of 5.35 and 5.65 by electrofocusing in 5% polyacrylamide gels. Their optimum pHs of enzyme activity were 6.5 as determined by using nephrectomized rat plasma as a substrate. Their specific angiotensin I (Ang I) generation activities were 158 and 146 micrograms of Ang I (microgram of protein)-1 h-1, respectively, which correspond to 1100 and 1020 Goldblatt units (mg of protein)-1 h-1. The three cathepsins showed molecular weights of 41 000, 43 000, and 41 000 by gel filtration and 46 000, 45 000, and 46 000 by SDS gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)


Non-Markov character of the phase fluctuations for sound propagation over relatively small ranges in the turbulent atmosphere.
The Markov approximation significantly simplifies formulations for the statistical moments of a wave propagating in a random medium. For the phase fluctuations, the Markov approximation is expected to be valid if the propagation range is much greater than the scale of largest inhomogeneities in a medium. In the atmospheric boundary layer, this scale can be several hundred meters, indicating that the Markov approximation might be inapplicable for relatively small ranges. In this paper, using geometrical acoustics, the correlation function and variance of the phase fluctuations of a plane sound wave are calculated without the Markov approximation and compared to previous results based on this approximation. The mean sound field and the spatial mutual coherence function (MCF) are also analyzed by expressing them in terms of the phase fluctuations. It is shown that for ranges smaller than the scale of largest inhomogeneities, the variance of the phase fluctuations is significantly smaller than that found with the Markov approximation. For large ranges, the relative difference between the two results tends to zero, while the absolute difference remains constant and can be much greater than unity. For the MCF, the Markov approximation is valid for both small and large ranges.


Evaluation of the Merlin MICRONAUT system for rapid direct susceptibility testing of gram-positive cocci and gram-negative bacilli from positive blood cultures.
Bloodstream infections are life-threatening conditions which require the timely initiation of appropriate antimicrobial therapy. We evaluated the automated Merlin MICRONAUT system for rapid direct microtiter broth antimicrobial susceptibility testing (AST) of gram-positive cocci and gram-negative bacilli from BACTEC 9240 bottles with positive blood cultures in comparison to the standard method for the Merlin MICRONAUT system. This prospective study was conducted under routine working conditions during a 9-month period. Altogether, 504 isolates from 409 patients and 11,819 organism-antibiotic combinations were evaluated for comparison of direct and standard AST methods. For gram-negative bacilli, direct and standard AST of 110 isolates was evaluated and MIC agreement was found for 98.1% of 2,637 organism-antibiotic combinations. Category (susceptible, intermediate susceptible, resistant [SIR]) agreement was found for 99.0%, with results for 0.04% of combinations showing very major errors, those for 0.2% showing major errors, and those for 0.8% showing minor errors. For gram-positive cocci, 373 isolates were evaluated and MIC agreement was found for 95.6% of 8,951 organism-antibiotic combinations. SIR agreement was found for 98.8%, with results for 0.3% of combinations showing very major errors, those for 0.4% showing major errors, and those for 0.5% showing minor errors. Although the number of tested isolates was limited (n = 33), direct AST of streptococci was performed for the first time, yielding promising results with SIR agreement for 98.6% of 363 organism-antibiotic combinations. In conclusion, direct AST of gram-negative bacilli and gram-positive cocci from positive blood cultures with the MICRONAUT system is a reliable technique that allows for the omission of repeat testing of subcultured isolates. Thereby, it reduces the time to results of blood culture testing and may have a positive impact on patient care.


Heart in An Eggshell Calcification: Idiopathic Calcific Constrictive Pericarditis.
Constrictive pericarditis is caused by fibrosis and calcification of the pericardium, which inhibits diastolic filling of the heart. Chest roentgenogram can show the calcification as a mass or sheet over the heart and computed tomography scan allows anatomic delineation of the pericardium and determines the extent of calcification. We reported a case of eggshell calcification of idiopathic chronic constrictive pericarditis diagnosed by echocardiography and multi-detector computed tomography.


An alternative start regimen with aripiprazole once-monthly in patients with schizophrenia: population pharmacokinetic analysis of a single-day, two-injection start with gluteal and/or deltoid intramuscular injection.
The single-injection start regimen for aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia requires a single intramuscular injection in the gluteal or deltoid site and 14 days of concurrent oral therapy. A simplified, single-day regimen of two injections at separate gluteal and/or deltoid injection sites, together with a single 20-mg dose of oral aripiprazole on the 1st day, was assessed. A previously developed population-pharmacokinetic (popPK) model for characterizing aripiprazole PK following oral administration and gluteal intramuscular depot injection was expanded to include deltoid injection. Simulations were conducted to assess PK profiles following various (including two-injection) start regimens. Postmarketing data on patients who received higher-than-recommended AOM doses were used to assess overall safety/tolerability. The two-injection start regimen with a single concurrent oral dose displayed a comparable PK profile to the single-injection start regimen with concurrent 14-day oral administration in simulations. The safety assessment indicated the two-injection start regimen was unlikely to be associated with safety concerns beyond those expected with a single-injection start regimen. These data support use of the two-injection start regimen in clinical practice to reduce reliance on daily oral administration and optimize the therapeutic benefits of AOM 400 in patients with schizophrenia.


Response of net reduction rate in vegetation carbon uptake to climate change across a unique gradient zone on the Tibetan Plateau.
The Tibetan Plateau (TP) has a variety of vegetation types that range from alpine tundra to tropic evergreen forest, which play an important role in the global carbon (C) cycle and is extremely vulnerable to climate change. The vegetation C uptake is crucial to the ecosystem C sequestration. Moreover, net reduction in vegetation C uptake (NRVCU) will strongly affect the C balance of terrestrial ecosystem. Until now, there is limited knowledge on the recovery process of vegetation net C uptake and the spatial-temporal patterns of NRVCU after the disturbance that caused by climate change and human activities. Here, we used the MODIS-derived net primary production to characterize the spatial-temporal patterns of NRVCU. We further explored the influence factors of the net reduction rate in vegetation C uptake (NRRVCU) and recovery processes of vegetation net C uptake across a unique gradient zone on the TP. Results showed that the total net reduction amount of vegetation C uptake gradually decreased from 2000 to 2015 on the TP (Slope = -0.002, P < 0.05). Specifically, an increasing gradient zone of multi-year average of net reduction rate in vegetation carbon uptake (MYANRRVCU) from east to west was observed. In addition, we found that the recovery of vegetation net C uptake after the disturbance caused by climate change and anthropogenic disturbance in the gradient zone were primarily dominated by precipitation and temperature. The findings revealed that the effects of climate change on MYANRRVCU and vegetation net C uptake recovery differed significantly across geographical space and vegetation types. Our results highlight that the biogeographic characteristics of the TP should be considered for combating future climate change.


Renal actions of endothelin peptides.
In the past year, major advances have been made in understanding the role of endothelin peptides in renal homeostasis. Numerous cells in the kidney secrete endothelin, which binds to two receptor subtypes on neighboring cells in an autocrine or paracrine mode. Endothelin is a potent vasoconstrictor of the renal vasculature that reduces renal blood flow and glomerular filtration rate. Endothelin also affects renal sodium and water handling. Finally, we may have to extend our concept of the renal actions of endothelin to include its growth factor actions.


Formal [3 + 3] cycloaddition approach to chromenes and chromanes. Concise total syntheses of (+/-)-rhododaurichromanic acids A and B and methyl (+/-)-daurichromenic ester.
[reaction: see text] Total syntheses of (+/-)-rhododaurichromanic acids A and B and methyl (+/-)-daurichromenic ester are described here. Despite the complex appearances of these compounds, their syntheses are completed in six steps with a 15% overall yield as a mixture by featuring our formal oxa-[3 + 3] cycloaddition methodology.


Gene expression profiles in primary duodenal chick cells following transfection with avian influenza virus H5 DNA plasmid encapsulated in silver nanoparticles.
In order to develop a systemically administered safe and effective nonviral gene delivery system against avian influenza virus (AIV) that induced cytokine expression, the hemagglutinin (H5) gene of AIV, A/Ck/Malaysia/5858/04 (H5N1) and green fluorescent protein were cloned into a coexpression vector pIRES (pIREGFP-H5) and formulated using green synthesis of silver nanoparticles (AgNPs) with poly(ethylene glycol) and transfected into primary duodenal cells taken from 18-day-old specific-pathogen-free chick embryos. The AgNPs were prepared using moderated temperature and characterized for particle size, surface charge, ultraviolet-visible spectra, DNA loading, and stability. AgNPs and AgNP-pIREGFP-H5 were prepared in the size range of 13.9 nm and 25 nm with a positive charge of +78 ± 0.6 mV and +40 ± 6.2 mV, respectively. AgNPs with a positive surface charge could encapsulate pIREGFP-H5 efficiently. The ultraviolet-visible spectra for AgNP-pIREGFP-H5 treated with DNase I showed that the AgNPs were able to encapsulate pIREGFP-H5 efficiently. Polymerase chain reaction showed that AgNP-pIREGFP-H5 entered into primary duodenal cells rapidly, as early as one hour after transfection. Green fluorescent protein expression was observed after 36 hours, peaked at 48 hours, and remained stable for up to 60 hours. In addition, green fluorescent protein expression generally increased with increasing DNA concentration and time. Cells were transfected using Lipocurax in vitro transfection reagent as a positive control. A multiplex quantitative mRNA gene expression assay in the transfected primary duodenal cells via the transfection reagent and AgNPs with pIREGFP-H5 revealed expression of interleukin (IL)-18, IL-15, and IL-12β.


Identification of chemosensory proteins for trichloroethylene in Pseudomonas aeruginosa.
The involvement of the chemotaxis gene cluster 1 (cheYZABW) and cheR in repellent responses of Pseudomonas aeruginosa to trichloroethylene (TCE) is described and three methyl-accepting chemotaxis proteins (MCPs) for TCE are identified. TCE chemotaxis assays of a number of deletion-insertion mutants of P. aeruginosa PAO1 revealed that the chemotaxis gene cluster 1 and cheR are required for negative chemotaxis to TCE. Mutant strains which contained deletions in pctA, pctB and pctC showed decreased responses to TCE. The pctA, pctB and pctC genes have been reported to encode MCPs for amino acids [K. Taguchi et al., Microbiology, 143, 3223--3229 (2000)]. The pctA mutation more severely impaired chemotactic responses to TCE than did those of pctB and pctC, suggesting that PctA is the major MCP for TCE among the three MCPs. The pctA, pctB and pctC mutant strains showed decreased responses to chloroform and methylthiocyanate. This result demonstrates that PctA, PctB and PctC are also involved in repellent responses to chloroform and methylthiocyanate.


Refractive Status and Biometric Characteristics of Children With Familial Exudative Vitreoretinopathy.
To compare biometric characteristics between patients with early-stage familial exudative vitreoretinopathy (FEVR) and healthy controls. This case-control study included 50 FEVR eyes in stage 1-2 and 50 control eyes matched by age, gender and spherical equivalent (SE). Biometric parameters including axial length (AL), white-to-white diameter (WTW), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), pupil diameter, vitreous chamber depth, anterior and posterior corneal surface curvature radius (ACR and PCR), anterior lens surface curvature radius (ALR) and posterior lens surface curvature radius were measured using IOLMaster 700 and compared between cases and controls using paired t-test. Correlations between SE and biometric measures were assessed using Pearson correlation coefficient (r) in cases and controls. Both FEVR cases and matched controls had a mean age of 7.6 years, 48% female and mean SE of -5.3 D (80% myopia). Compared to controls, FEVR eyes had smaller AL (P = 0.009), WTW (P = 0.001), ACD (P < 0.001), and ALR (P = 0.03), but larger CCT (P = 0.02) and LT (P = 0.01). In FEVR eyes, SE was negatively correlated with AL (r = -0.79, P < 0.001), positively correlated with ACR (r = 0.29, P = 0.04) and PCR (r = 0.33, P = 0.02), whereas in controls, SE was negatively correlated with AL (r = -0.82, P < 0.001) and LT (r = -0.34, P = 0.02), positively correlated with ALR (r = 0.29, P = 0.04). Patients at early stage of FEVR exhibited a unique eye morphology resembling ocular development arrest, which may help to develop screening and early detection tools for FEVR. In FEVR patients, myopia is very prevalent and significantly associated with corneal curvature increase.


Pyrocarbon hemiarthroplasty and the shoulder: biomechanical and clinical results of an emerging treatment option.
While shoulder hemiarthroplasty is still used to treat young patients with shoulder pathology, the use of this procedure has substantially declined in recent years due to its significant complication profile. Glenoid wear with arthrosis is one of the major postoperative complications following shoulder hemiarthroplasty, and efforts to prevent this complication led many scientists to explore alternative weight-bearing surfaces on arthroplasty implants to decrease joint wear and improve patient outcomes. Pyrolytic carbon, or pyrocarbon, is a material that has better biocompatibility, survivorship, strength, and wear resistance compared to the materials used in traditional shoulder hemiarthroplasty. Pyrocarbon implants have been used in orthopedics for over 50 years; recently, their utility in shoulder hemiarthroplasty has garnered much interest. The purpose behind the use of pyrocarbon in shoulder hemiarthroplasty is to decrease the risk of progressive glenoid wear, especially in young active patients in whom joint preservation is important. Promising survivorship and outcomes have been demonstrated by recent studies, including limited glenoid wear following pyrocarbon hemiarthroplasty. Nevertheless, these clinical studies have been limited to relatively small case series with limited long-term follow-up. Accordingly, additional research and comparative studies need to be conducted in order to properly assess the therapeutic efficacy and value of pyrocarbon hemiarthroplasty.


Giant-cell tumor of bone with pulmonary metastases. Six case reports and a review of the literature.
Giant-cell tumor of bone rarely metastasizes to the lung. In three of six cases, lesions in lung tissue were histologically benign. In 39 such cases reported in the literature, the treatments were surgical extirpation, chemotherapy, and radiation therapy. Resection was indicated to definitely diagnose the pulmonary lesions as benign giant-cell tumors. Radiation therapy and/or chemotherapy may be beneficial as adjuvant treatment, especially where the lesions are anatomically inaccessible. Some pulmonary lesions spontaneously regress even in the absence of definitive treatment.


Prognostic value of SUVmax in breast cancer and comparative analyses of molecular subtypes: A systematic review and meta-analysis.
To assess the prognostic capability of the maximum standardized uptake values (SUVmax) measured in the primary tumor and axillary lymph nodes (ALNs) by pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography and analyze outcomes according to the molecular breast cancer subtypes. The databases were systematically searched using keywords for breast cancer, positron emission tomography/computed tomography, and SUVmax; the extracted studies reported at least 1 form of survival data, event-free survival (EFS) and overall survival. Comparative analyses of the pooled hazard ratios (HRs) for EFS and overall survival were performed to assess their correlations with SUVmax. The pooled HR was estimated using random-effects model according to the results of heterogeneity. Thirteen eligible studies comprising 3040 patients with breast cancer were included. The pooled HRs of high SUVmax in the primary tumor and ALN were 3.01 (95% CI 1.83-4.97, P < .00001; I2 = 82%) and 3.72 (95% CI 1.15-12.01; I2 = 92%; P = .03), respectively. Patients with higher SUVmax demonstrated a poorer survival prognosis. Furthermore, comparative analyses according to the molecular subtypes demonstrated that the SUVmax in the primary tumor or ALN can be a predictive parameter in patients with the luminal subtype disease. Subtype analysis results indicated a significant association of the luminal group, with a HR of 2.65 (95% CI 1.31-5.37; I2 = 27%; P = .007). SUVmax from pretreatment is a significant prognostic factor for EFS in patients with breast cancer. Despite several limitations, correlation with molecular subtype (luminal type) was demonstrated. Further large-scale studies are required to investigate the precise prognostic capability of SUVmax.


In Patients Undergoing Cochlear Implantation, Psychological Burden Affects Tinnitus and the Overall Outcome of Auditory Rehabilitation.
Cochlear implantation (CI) is increasingly being used in the auditory rehabilitation of deaf patients. Here, we investigated whether the auditory rehabilitation can be influenced by the psychological burden caused by mental conditions. Our sample included 47 patients who underwent implantation. All patients were monitored before and 6 months after CI. Auditory performance was assessed using the Oldenburg Inventory (OI) and Freiburg monosyllable (FB MS) speech discrimination test. The health-related quality of life was measured with Nijmegen Cochlear implantation Questionnaire (NCIQ) whereas tinnitus-related distress was measured with the German version of Tinnitus Questionnaire (TQ). We additionally assessed the general perceived quality of life, the perceived stress, coping abilities, anxiety levels and the depressive symptoms. Finally, a structured interview to detect mental conditions (CIDI) was performed before and after surgery. We found that CI led to an overall improvement in auditory performance as well as the anxiety and depression, quality of life, tinnitus distress and coping strategies. CIDI revealed that 81% of patients in our sample had affective, anxiety, and/or somatoform disorders before or after CI. The affective disorders included dysthymia and depression, while anxiety disorders included agoraphobias and unspecified phobias. We also diagnosed cases of somatoform pain disorders and unrecognizable figure somatoform disorders. We found a positive correlation between the auditory performance and the decrease of anxiety and depression, tinnitus-related distress and perceived stress. There was no association between the presence of a mental condition itself and the outcome of auditory rehabilitation. We conclude that the CI candidates exhibit high rates of psychological disorders, and there is a particularly strong association between somatoform disorders and tinnitus. The presence of mental disorders remained unaffected by CI but the degree of psychological burden decreased significantly post-CI. The implants benefitted patients in a number of psychosocial areas, improving the symptoms of depression and anxiety, tinnitus, and their quality of life and coping strategies. The prevalence of mental disorders in patients who are candidates for CI suggests the need for a comprehensive psychological and psychosomatic management of their treatment.


[Analysis on the stationed system for detached medical officer in the Song Dynasty].
The stationed system for detached medical officer, designated by the Royal Hanlin Department, was an important management system in the Song Dynasty for medical aid and epidemic prevention. The selection of the officers was based on the test results of the candidates. The dispatch of such medical officers was considered comprehensively on the local conditions, with priority given to those provinces and counties in shortage of such officers, and sent them in order based on the duration of their working time.The primary responsibility of the stationed medical officers was to provide medical services to locally stationed troops, at the same time also involved in treating and saving people as epidemics occurred in local places. The term of their service was two years. The system is a kind of relatively mature medical management practices, which could improve the level of local army medical services and control the occurrence and spread of epidemics effectively.


Expanding the coverage of regulons from high-confidence prior knowledge for accurate estimation of transcription factor activities.
Gene regulation plays a critical role in the cellular processes that underlie human health and disease. The regulatory relationship between transcription factors (TFs), key regulators of gene expression, and their target genes, the so called TF regulons, can be coupled with computational algorithms to estimate the activity of TFs. However, to interpret these findings accurately, regulons of high reliability and coverage are needed. In this study, we present and evaluate a collection of regulons created using the CollecTRI meta-resource containing signed TF-gene interactions for 1186 TFs. In this context, we introduce a workflow to integrate information from multiple resources and assign the sign of regulation to TF-gene interactions that could be applied to other comprehensive knowledge bases. We find that the signed CollecTRI-derived regulons outperform other public collections of regulatory interactions in accurately inferring changes in TF activities in perturbation experiments. Furthermore, we showcase the value of the regulons by examining TF activity profiles in three different cancer types and exploring TF activities at the level of single-cells. Overall, the CollecTRI-derived TF regulons enable the accurate and comprehensive estimation of TF activities and thereby help to interpret transcriptomics data.


Inflammasome in Skeletal Muscle: NLRP3 Is an Inflammatory Cell Stress Component in Inclusion Body Myositis.
Inclusion body myositis (IBM) is a chronic, mostly treatment-resistant, inflammatory myopathy with a pathology that centers around specific interactions between inflammation and protein accumulation. The study aimed to identify the inflammasome as a key event in the complex network of pathomechanisms. Regulation of the inflammasome was assessed in a well-established pro-inflammatory cell culture model using human myoblasts and primary human myotubes. By quantitative PCR, western blot and immunocytochemistry, inflammasome markers including NLRP3 were assessed in muscle cells exposed to the cytokines IL-1β and IFN-γ. The data were corroborated by analysis of muscle biopsies from patients with IBM compared to other myositis subtypes. In the cell culture model of IBM, the NLRP3 inflammasome was significantly overexpressed, as evidenced by western blot (p = 0.03) and quantitative PCR (p < 0.01). Target genes that play a role in inflammasome assembly, T-cell migration, and MHC-I expression (p = 0.009) were highly co-upregulated. NLRP3 was significantly overexpressed in muscle biopsies from IBM samples compared to disease controls (p = 0.049), including other inflammatory myopathies. Due to the extraordinary features of the pathogenesis and the pronounced upregulation of NLRP3 in IBM, the inflammasome could serve as a key molecule that drives the inflammatory cascade as well as protein accumulation in the muscle. These data can be useful for future therapeutic developments.


One-pot laccase-catalysed synthesis of 5,6-dihydroxylated benzo[b]furans and catechol derivatives, and their anticancer activity.
A commercial laccase, Suberase® from Novozymes, was used to catalyse the synthesis of 5,6-dihydroxylated benzo[b]furans and catechol derivatives. The yields were, in some cases, similar to or better than that obtained by other enzymatic, chemical or electrochemical syntheses. The synthesised derivatives were screened against renal (TK10), melanoma (UACC62), breast (MCF7) and cervical (HeLa) cancer cell lines. GI50, TGI and LC50 are reported for the first time. Anticancer screening showed that the cytostatic effects of the 5,6-dihydroxylated benzo[b]furans were most effective against the melanoma (UACC62) cancer cell line with several compounds exhibiting potent growth inhibitory activities (GI50=0.77-9.76 µM), of which two compounds had better activity than the anticancer agent etoposide (GI50 0.89 µM). One compound exhibited potent activity (GI50=9.73 µM) against the renal (TK10) cancer cell line and two exhibited potent activity (GI50=8.79 and 9.30 µM) against the breast (MCF7) cancer cell line. These results encourage further studies of the 5,6-dihydroxylated benzo[b]furans for their potential application in anticancer therapy.


Solution phase parallel synthesis of substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5-a]quinazolines: selective serotonin 5-HT(6) receptor antagonists.
Here we present the solution phase parallel synthesis of a combinatorial library consisting of 776 new substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5-a]quinazolines and a study of the relation of their structure with a 5-HT(6) receptor antagonistic activity in a functional cell (HEK 293) analysis and radioligand competitive binding. We have found highly active and selective 5-HT(6)R antagonists. The most active 5-HT(6)R antagonists have IC(50) <100 nM in a functional assay, and K(i) <10 nM in a binding assay, which is 100 times higher than the activity with respect to other serotonin receptors.


The Route to HPV-Associated Neoplastic Transformation: A Review of the Literature.
Human papillomaviruses (HPVs)-small, nonenveloped viruses with double-stranded circular DNA-are believed to have a role in the progression of cancer. However, the exact mechanisms are not well established. The interference of HPV proteins, especially E6 and E7, in the cell cycle is considered to be the main pathway. It is still questioned whether the expression of these proteins or the viral load is more important in neoplastic transformation. Furthermore, HPV is believed to adapt mechanisms to evade the host cell immune system; persistent HPV infection may also play a role in oncogenic transformation by causing genomic instability and local immune suppression. These factors may cause accumulation of genomic alterations within the host cell and integration of the viral genome into the host genome. In recent years, epigenetic modifications, such as methylation, have also been considered to take part in neoplastic transformation. All of these alterations to the genome may be favorable to the development of cancer. This article highlights the association of HPV in neoplastic transformation and cancer progression.


Predictive factors for visual acuity after intravitreal triamcinolone treatment for diabetic macular edema.
To evaluate which factors influence maximum gain in best-corrected visual acuity after intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema. This prospective clinical interventional study included 53 eyes with diffuse diabetic macular edema receiving an intravitreal injection of about 20 mg of triamcinolone. The mean +/- SD follow-up was 10.2 +/- 7.6 months. In a multiple linear regression analysis, maximum gain in best-corrected visual acuity after the intravitreal injection of triamcinolone was significantly (P < .001) and negatively correlated with an increased degree of macular ischemia and a higher preoperative visual acuity. Improvement in best-corrected visual acuity was significantly and positively correlated with increased degree of macular edema (P = .001). Change in best-corrected visual acuity after the intravitreal triamcinolone injection was statistically independent (P > .15) of age, sex, pseudophakia, and macula grid laser treatment before inclusion into the study. The results were comparable for gain in visual acuity at 6 months after the injection. Pronounced macular edema may have a positive impact, and marked macular ischemia and a high preoperative best-corrected visual acuity may have a negative impact, on an increase in best-corrected visual acuity after intravitreal triamcinolone injection in patients with diabetic macular edema.


The appearance of the UmuD'C protein complex in Escherichia coli switches repair from homologous recombination to SOS mutagenesis.
The process of SOS mutagenesis in Escherichia coli requires (i) the replisome enzymes, (ii) RecA protein, and (iii) the formation of the UmuD'C protein complex which appears to help the replisome to resume DNA synthesis across a lesion. We found that the UmuD'C complex is an antagonist of RecA-mediated recombination. Homologous recombination in an Hfr x F- cross decreased as a function of the UmuD'C cell concentration; this effect was challenged by increasing RecA concentration. Recombination of a u.v.-damaged F-lac with the lac gene of an F- recipient was reduced by increasing the UmuD'C concentration while lac mutagenesis increased, showing an inverse relationship between recombination and SOS mutagenesis. We explain our data with the following model. The kinetics of appearance of the UmuD'C complex after DNA damage is slow, reaching a maximum after an hour. Within that period, excision and recombinational repair have had time to occur. When the UmuD'C concentration relative to the number of residual RecA filaments, not resolved by recombinational repair, becomes high enough, UmuD'C proteins provide a processive factor for the replisome to help replication bypass and repel the standing RecA filament. Thus, at a high enough concentration, the UmuD'C complex will switch repair from recombination to SOS mutagenesis.


Management of Aneurysmal Subarachnoid Haemorrhage and its Complications: A Clinical Guide.
Aneurysmal subarachnoid hemorrhage (aSAH) is an emergency that needs prompt diagnosis and treatment with endovascular coiling or surgical clipping of the aneurysm to prevent re-bleeding. In addition to neurologic manifestations, aSAH can cause respiratory and cardiovascular complications. The prevention of hypoxemia and hypercarbia, control of intracranial pressure, and restoration of cerebral perfusion pressure should be the primary aims of early management. Secondarily, the most important causes of persistent neurological deficits and physical dependence in aSAH are vasospasm and delayed ischemia following bleeding. During that period, a focus on the detection, prevention, and treatment of vasospasm should be the rule. Transcranial Doppler allows detection and follow-up of vasospasm, especially in severe cases. Nimodipine is the only drug that has proven efficacy for treating vasospasm. Balloon angioplasty is performed in cases of resistance to medical treatment. Along with angioplasty, intra-arterial vasodilators can be administered. New diagnostic and therapeutic advances will hopefully improve outcomes in the near future.


How Multidimensional Health Locus of Control predicts utilization of emergency and inpatient hospital services.
Health locus of control may be an important predictor of health care utilization. We analyzed associations between health locus of control and frequency of emergency department visits and hospital admissions, and investigated self-rated health as a potential mediator. Overall, 863 patients in an urban emergency department completed the Multidimensional Health Locus of Control instrument, and self-reported emergency department use and hospital admissions in the last year. We found small but significant associations between Multidimensional Health Locus of Control and utilization, all of which were mediated by self-rated health. We conclude that interventions to shift health locus of control may change patients' perceptions of their own health, thereby impacting utilization.


All-fiber wavelength swept ring laser based on Fabry-Perot filter for optical frequency domain imaging.
Innovations in laser engineering have yielded several novel configurations for high repetition rate, broad sweep range, and long coherence length wavelength swept lasers. Although these lasers have enabled high performance frequency-domain optical coherence tomography, they are typically complicated and costly and many require access to proprietary materials or devices. Here, we demonstrate a simplified ring resonator configuration that is straightforward to construct from readily available materials at a low total cost. It was enabled by an insight regarding the significance of isolation against bidirectional operation and by configuring the sweep range of the intracavity filter to exceed its free spectral range. The design can easily be optimized to meet a range of operating specifications while yielding robust and stable performance. As an example, we demonstrate 240 kHz operation with 125 nm sweep range and >70 mW of average output power and demonstrate high quality frequency domain OCT imaging. The complete component list and directions for assembly of the laser are posted on-line at www.octresearch.org.


Molecular, Local, and Network-Level Basis for the Enhanced Stiffness of Hydrogel Networks Formed from Coassembled Racemic Peptides: Predictions from Pauling and Corey.
Hydrogels prepared from self-assembling peptides are promising materials for medical applications, and using both l- and d-peptide isomers in a gel's formulation provides an intuitive way to control the proteolytic degradation of an implanted material. In the course of developing gels for delivery applications, we discovered that a racemic mixture of the mirror-image β-hairpin peptides, named MAX1 and DMAX1, provides a fibrillar hydrogel that is four times more rigid than gels formed by either peptide alone-a puzzling observation. Herein, we use transmission electron microscopy, small angle neutron scattering, solid state NMR, diffusing wave, infrared, and fluorescence spectroscopies, and modeling to determine the molecular basis for the increased mechanical rigidity of the racemic gel. We find that enantiomeric peptides coassemble in an alternating fashion along the fibril long axis, forming an extended heterochiral pleat-like β-sheet, a structure predicted by Pauling and Corey in 1953. Hydrogen bonding between enantiomers within the sheet dictates the placement of hydrophobic valine side chains in the fibrils' dry interior in a manner that allows the formation of nested hydrophobic interactions between enantiomers, interactions not accessible within enantiomerically pure fibrils. Importantly, this unique molecular arrangement of valine side chains maximizes inter-residue contacts within the core of the fibrils resulting in their local stiffening, which in turn, gives rise to the significant increase in bulk mechanical rigidity observed for the racemic hydrogel.


Granulocyte colony-stimulating factor prevents progression of monocrotaline-induced pulmonary arterial hypertension in rats.
Regeneration of the lung microvasculature and replacing pulmonary artery lesions with functional endothelial cells could be a novel and effective therapeutic strategy for treating advanced pulmonary arterial hypertension (PAH). In the present study it was postulated that granulocyte colony-stimulating factor (G-CFS), which induces the proliferation of endothelial cells, would stimulate endothelial regeneration in situ at sites of impaired lung vasculature and prevent the development of PAH. Daily administration of G-CSF for 48 days did not affect the hemodynamism of normal Fischer 344 rats. PAH was induced with monocrotaline (60 mg/kg) and G-CSF was administered daily (100 microg/kg per day). Echocardiographic findings and an invasive catheter study indicated a significant decrease in the progression of PAH in rats given G-CSF. Furthermore, G-CSF increased Ki-67 positivity in the pulmonary arteries of PAH rats but did not accelerate c-kit positive cell recruitment into peripheral blood. Daily doses of G-CSF at both 2 and 100 microg/kg improved the survival and body weight gain of PAH rats. G-CSF improved the progression of PAH in a rat model, possibly by stimulating pulmonary endothelial cells to proliferate at sites of impaired lung vasculature. These findings show that cytokine therapy for PAH is valid based on the concept of vascular regeneration.


The efficacy of HPV 16/18 vaccines on sexually active 18-23 year old women and the impact of HPV vaccination on organized cervical cancer screening.
Evaluate the efficacy of catch-up HPV vaccination in sexually active young women and the potential impact of HPV vaccines on the practice of organized screening. (1) Women enrolled in the Future II study and (2) from a separate population-based study in Iceland. (1) Analysis of cytological and histological results and colposcopic examinations among 710 women, aged 18-23, with less than five sexual partners, irrespectively of baseline HPV status at enrolment. (2) The impact on screening practice as determined by evaluating the distribution of 12 oncogenic HPV types in 582 cervical intraepithelial lesions (CIN 2-3) and cancer cases. (1) Distribution of evaluated parameters according to age at enrolment. (2) Age distribution of four HPV groups, within age classes and HPV groups: mean time to development of lesions, mean time to development of CIN 2-3+, cumulative frequency for CIN 2-3+ lesions after the last normal smear. (1) After an average 52 months of post-enrolment follow-up, significant reductions in all evaluated parameters were observed in women aged 18-19 at enrolment. (2) Among women <25 years, the proportion of cases with only HPV 16/18 was significantly lower and the proportion containing HPV16/18 plus > or =1 out of 10 non-vaccine HPV types (31/33/45/52/58/35/39/51/56/59) was higher than at age 25-49. The proportion of cases containing only the non-vaccine types was the same within all age groups. Cases with HPV 16/18 and some non-vaccine types decreased significantly with age and accumulated more slowly after the last negative smear. Catch-up vaccination of younger women should be considered in the context of sexual practices and the effects of prevalent disease on observed vaccine efficacy. Current data do not support a change in the lower age limit or screening intervals for women.


Addendum to the German Consensus Recommendations on Ponatinib in the Treatment of Chronic Myeloid Leukemia.
Based on the new data from the primary analysis of the OPTIC (Optimizing Ponatinib Treatment in CP-CML) trial on dose optimization of ponatinib in patients with chronic phase (CP)-CML, the German consensus paper on ponatinib published in 2020 (Saussele S et al., Acta Haematol. 2020) has been updated in this addendum. Focus is on the update of efficacy and safety of ponatinib, reflecting the new data set, as well as the update of the benefit-risk assessment and recommendations for ponatinib starting dose in CP-CML - provided that the decision to use ponatinib has already been made. Furthermore, based on OPTIC and additional empirical data, the expert panel collaborated to develop a decision tree for ponatinib dosing, specifically for intolerant and resistant patients. The recommendations on cardiovascular management have also been updated based on the most recent 2021 guidelines of the European Society of Cardiology (ESC) on cardiovascular disease (CVD) prevention in clinical practice. The OPTIC data confirm the high efficacy of ponatinib in patients with CP-CML and provide the basis for individualized dose adjustment during the course of treatment.


[Reliability of modified Rankin Scale assessment with a Japanese version of simplified modified Rankin Scale Questionnaire (J-RASQ)].
Modified Rankin Scale (mRS) is widely used as an indicator of physical disability after the onset of stroke and a main evaluation scale in clinical stroke trials but sometimes has discrepancies among raters. We designed a Japanese version of simplified mRS questionnaire (J-RASQ) to evaluate mRS using closed question to assess the difference from the original. Currently there are no Japanese version of mRS questionnaire and its validity and reliability assessment has been warranted. Patients with planned visit to our hospital between 60 and 120 days after the onset of cerebral hemorrhage or infarction between August 2017 and March 2018 were recruited. J-RASQ was distributed before the outpatient visit to stroke patients, families or caregivers, and response was obtained. Thereafter, outpatient attending physicians qualified as stroke or neurological specialists evaluated mRS according to the Japanese version of guidance scheme for mRS. Subsequently, 130 patients (mean age, 72 ± 12 years old) were enrolled, and the difference between the two scale scores (mRS vs. J-RASQ) were statistically examined by the κ statistic and the weighted κ statistic. The κ statistic was 0.42 (95% CI, 0.31-0.52), and the weighted κ statistic calculated taking into account the extent of disagreement was 0.78 (95% CI, 0.70-0.86). We conclude that the J-RASQ appears to have decent reliability and is similar to the existing mRS.


Learning Empathy Through Simulation: A Systematic Literature Review.
Simulation is increasingly used as an educational methodology for teaching empathy to preservice health professional students. This systematic review aimed to determine if and how simulation, including games, simulated patients, and role-play, might develop empathy and empathetic behaviors in learners. Eleven databases or clearing houses including MEDLINE, EMBASE, CINAHL, PsychInfo, and ERIC were searched for all articles published from any date until May 2014, using terms relating to (i) preservice health professional students, (ii) simulation, and (iii) empathy. Twenty-seven studies met the inclusion criteria, including 9 randomized controlled trials. A narrative synthesis suggests that simulation may be an appropriate method to teach empathy to preservice health professional students and identifies the value of the learner taking the role of the patient.


Quercetin dual interaction at the membrane level.
Quercetin impact on lipid bilayers suggests a dual action mechanism at cell membranes. This widespread polyphenol displays high partition with low interference in the more fluid membrane domains, more vulnerable to oxidative attack, but strong perturbation of cholesterol/sphingolipid enriched domains, where signalling platforms are expected to assemble.


Deciphering the Role of the Barr Body in Malignancy: An insight into head and neck cancer.
X chromosome inactivation is the epitome of epigenetic regulation and long non-coding ribonucleic acid function. The differentiation status of cells has been ascribed to X chromosome activity, with two active X chromosomes generally only observed in undifferentiated or poorly differentiated cells. Recently, several studies have indicated that the reactivation of an inactive X chromosome or X chromosome multiplication correlates with the development of malignancy; however, this concept is still controversial. This review sought to shed light on the role of the X chromosome in cancer development. In particular, there is a need for further exploration of the expression patterns of X-linked genes in cancer cells, especially those in head and neck squamous cell carcinoma (HNSCC), in order to identify different prognostic subpopulations with distinct clinical implications. This article proposes a functional relationship between the loss of the Barr body and the disproportional expression of X-linked genes in HNSCC development.


Thiol-ene Photocrosslinking of Cytocompatible Resilin-Like Polypeptide-PEG Hydrogels.
A range of chemical strategies have been used for crosslinking recombinant polypeptide hydrogels, although only a few have employed photocrosslinking approaches. Here, we capitalize on the novel insect protein, resilin, and the versatility of click reactions to introduce a resilin-like polypeptide (RLP) that is capable of photoinitiated thiol-ene crosslinking. Lysine residues of the RLP were functionalized with norbornene acid as confirmed via 1H-NMR spectroscopy. The RLPNs were subsequently photocrosslinked with multi-arm PEG thiols in the presence of a photoinitiator to form elastic hybrid hydrogels. The crosslinking reaction and resulting RLP-PEG networks demonstrated cytocompatibility with human mesenchymal stem cells in both 2D cell-adhesion and 3D photoencapsulation studies.


Prevention of diffuse, minimal lymphatic "retention" with Robuvit®: a concept, supplement registry study.
The aim of this study was to evaluate the effects of the standardized supplement Robuvit® (oak wood extract) in defined diffuse, minimal lymphatic "retention" (DMLR). Robuvit® has already been investigated in both primary and secondary (post-surgical, post chemo-radiotherapy) lymphatic insufficiency. This registry included subjects with diffuse, minimal lymphatic "retention" (DMLR). The registry management groups included women with mild-moderate limb swelling using standard management (SM) as controls. A second, comparable group used prevention with Robuvit® at the dosage of 3 cp/day (300 mg/day) for 4 weeks. No tolerability problems or side effects were observed with the preventive supplementation. The management groups (34 women in total), including 18 women in Robuvit® and 16 in SM were comparable in age and baseline evaluations. After 4 weeks, in the Robuvit® group, edema scale values derived from ultrasound observations decreased significantly (P<0.05) at all measurement's sites, from the proximal (inguinal) level to the more distal (ankle-foot) level. No significant changes in edema were observed in control subjects. Generally, in areas with higher level of edema (distal areas at the foot and ankle), the edema decrease was larger than in more proximal, ultrasound measurement sites. Preventive Robuvit® supplementation appears to be safe and effective in controlling DMLR in subjects without significant or apparent clinical conditions. This preventive, concept study should be extended to a larger population for more meaningful observations.


Current and Emerging Therapies for Lupus Nephritis.
The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments.


Conformational fluctuations versus constraints in amino acid side chains: the evolution of information content from free amino acids to proteins.
Like all other complex biological systems, proteins exhibit properties not found in free amino acids (i.e., emergent properties). Here, we explore top-down constraints experienced by the residue side chains in proteins compared to amino acids in increasingly complex molecular environments: free amino acids, end-capped amino acids, and the central residue in an alpha-helical nonapeptide. The crystalline structure of the contractile protein profilin Ib and the enzyme trypsin were chosen as objects of study, and submitted to 10 ns molecular dynamics (MD) simulations. The results revealed increased conformational constraints on the side chains when going from the simpler to the more complex compounds. A Shannon entropy (SE) analysis of the conformational behavior of the side chains showed in most cases a progressive and marked decrease in the SE of the chi1 and chi2 dihedral angles. This is equivalent to stating that conformational constraints on the side chain of residues increase their information content and, hence, recognition specificity compared to free amino acids. In other words, the vastly increased information content of a protein relative to its free monomers is embedded not only in the tertiary structure of the backbone, but also in the conformational behavior of the side chains. The postulated implication is that both backbone and side chains, by virtue of being conformationally constrained, contribute to the protein's recognition specificity toward other macromolecules and ligands.


Microhardness Properties of Mineral Trioxide Aggregate and Calcium-enriched Mixture Cement Plugs at Different Setting Conditions.
Providing an apical stop in open apex roots is one of the endodontic challenges. The aim of present study was to compare the surface hardness of both mineral trioxide aggregate (MTA) and calcium-enriched mixture (CEM) cement at different setting situations. A total of 40 freshly extracted human teeth with a single root and normal apex and no obvious caries or curvatures were selected. The teeth were sectioned horizontally from the cement enamel junction and 2 mm above the apex. Standard technique was administered for cleaning and shaping of the canals. Open apex root canal was prepared by using Peso reamer. The prepared teeth were randomly divided into four groups in which two groups were filled by MTA and the other groups were filled by CEM. White MTA and CEM cement plugs were prepared and condensed up to the apical end. In two groups, moistened paper point was placed in the canals and in the other group dried paper points was used. Vickers test was done to evaluate the microhardness and the collected data were analyzed by Kruskal-Wallis and three-way ANOVA tests using SPSS software version 18 at a significant level of 0.05. The highest and lowest surface hardness was observed in CEM group at dried condition with 4 mm thickness indentation (145.10 ± 7.60 kg/mm(2)) and moist MTA group indented at 8 mm thickness (111.25 ± 5.37 kg/mm(2)). However, no significant difference was noticed (P > 0.05). Humidity condition might not influence the microhardness properties of both MTA and CEM cement apical plugs at different tested indentation thickness.


Antidromic response to medullary pyramid stimulation in rats and its relation to that in cats.
The response evoked in the cerebral cortex of laboratory rats after stimulation of the medullary pyramid is surface-positive. It begins 0.9-1.6 ms after the stimulus, attains peak amplitude (up to 2 mV) in 0.8-1.2 ms and lasts 2-4 ms. It occurs throughout the anterior two-thirds of the dorsal cortex and is largest lateral to bregma, with a secondary maximum in the somatosensory area II. Although it depends on antidromic conduction in pyramidal tract fibers for its production, it varies in amplitude, configuration and latency at different recording sites and at the same sites on repeated trials. It reverses polarity deep in the cortex to become a large, negative wave deep in layer V, and maintains that polarity into the white matter. Current source density analysis reveals a strong sink in layer V, with a strong source just superficial to that sink and a weaker source in layer VI. The antidromic response disappears during spreading depression, but recovers more rapidly than the primary response evoked by skin stimulation. It decreases progressively in amplitude with continuous 200-Hz iterative stimulation, and recovers slowly at the end of stimulation. The primary response evoked by contralateral forepaw and hindpaw stimulation is highly localized, being entirely within the antidromic response distribution. The antidromic response in laboratory rats consists of a small, surface-positive component analogous to the pure antidromic response of cats, and of a large, surface-positive response analogous to that found in woodchucks, rabbits, opossums and slow lorises. It is argued that this latter response results from synaptic action in pyramidal tract axon collaterals, probably onto cells in layer V, rather than being a purely antidromic event.


Adverse psychosocial working conditions and risk of severe depressive symptoms. Do effects differ by occupational grade?
Depression is a major concern for public health. Both adverse working conditions and low socio-economic position are suspected to increase risk of depression. In a representative sample of the Danish workforce we investigated (i) whether adverse psychosocial working conditions, defined by the effort-reward imbalance (ERI) model, predicted onset of severe depressive symptoms after 5-year follow-up and (ii) whether the effect of ERI was differential across occupational grades. A cohort of 2701 Danish employees filled in a questionnaire on work and health in 2000 and 2005. ERI was measured with four effort and seven reward items. Depressive symptoms were assessed with the five-item Mental Health Inventory. Participants scoring ≤ 52 points were defined as cases. We used logistic regression to investigate the association of ERI and occupational grade in 2000 with onset of severe depressive symptoms in 2005. Analyses were adjusted for socio-demographics, health behaviours, survey method, self-rated health, sleep disturbances and non-severe depressive symptoms at baseline. High ERI predicted onset of severe depressive symptoms at follow-up, after adjustment for co-variates and occupational grade (OR = 2.19, 95% CI = 1.12-4.25). Participants with high ERI and low occupational grade showed a considerably higher OR (2.43, 95% CI = 1.07-5.53) compared to participants with low/medium ERI and low grade (OR = 1.45, 95% CI = 0.72-2.92), high ERI and high grade (OR = 1.26, 95% CI = 0.59-2.70) and low/medium ERI and high grade (reference group). Adverse psychosocial working conditions predicted onset of severe depressive symptoms. The effect was stronger among employees of lower occupational grades compared to those of higher grades.


Histiocytoid Sweet's syndrome presenting with annular erythematous plaques.
Histiocytoid Sweet's Syndrome is a rare inflammatory disease described in 2005 as a variant of the classical Sweet's Syndrome (SS). Histopathologically, the dermal inflammatory infiltrate is composed mainly of mononuclear cells that have a histiocytic appearance and represent immature myeloid cells. We describe a case of Histiocytoid Sweet's Syndrome in an 18-year-old man. Although this patient had clinical manifestations compatible with SS, the cutaneous lesions consisted of erythematous annular plaques, which are not typical for this entity and have not been described in histiocytic form so far. The histiocytic subtype was confirmed by histopathological analysis that showed positivity for myeloperoxidase in multiple cells with histiocytic appearance.


Blood lead levels and risk factors for lead poisoning among children in a Mexican smelting community.
The authors evaluated mean blood lead levels (BLLs) and the prevalence of elevated BLLs in children 1-6 yr of age living in Torreón, Mexico, and assessed risk factors for lead exposure in these children. The study involved a simple random sample of households in the area around a local smelter, as well as a 2-stage cluster sample of neighborhoods and households in the remainder of Torreón. The geometric mean BLL of children in this study (N = 367) was 6.0 microg/dl (95% confidence interval [CI] = 5.2, 6.8) (0.29 microM/l [95% CI = 0.25, 0.33]). Twenty percent of the children had BLLs > or = 10 microg/dl (0.48 microM/l), and 5% had BLLs > or = 20 microg/dl (0.97 microM/l). In multivariate analyses, distance from the smelter, amount of income, and education level of the primary caregiver predicted BLLs. In the environmental risk factor subsample (n = 124), dust and soil lead levels were associated with BLLs and distance from the smelter. BLLs in this study were moderately high, but the levels were lower than those in other smelting communities prior to remediation.


DELAYED MATURATION, NEOTENY, AND SOCIAL SYSTEM DIFFERENCES IN TWO MANAKINS OF THE GENUS CHIROXIPHIA.
Long-tailed manakins (Chiroxiphia linearis) and swallow-tailed manakins (C. caudata) are closely related, sexually dichromatic, lek-breeding species in which male mating success is highly skewed. Males of both species delay plumage maturation. Before reaching the definitive state, they wear a sequence of feather coats less conspicuous than that of the adult. Nondefinitive plumages probably enhance male survival in the two species; in C. caudata they may also enhance breeding success of young males, who may be fully reproductively mature their first year. In C. linearis testicular development is retarded along with that of plumage, although males may be physiologically capable of breeding prior to the acquisition of the definitive plumage. This difference probably reflects differences in the social systems of the two species. Five hypotheses have been proposed to explain the evolution of delayed plumage maturation. The sexual-selection, cryptic-breeder, and winter-adaptation hypotheses suggest that it functions primarily to enhance survival of young males. The juvenile- and female-mimicry hypotheses emphasize enhancement of immediate mating success. Support is provided for all but the female-mimicry hypothesis; it is argued that data are more consistent with juvenile mimicry and a neotenic origin of nondefinitive plumages.


Intracranial tumours in the elderly: diagnosis and treatment.
A series of 111 intracranial tumours in elderly patients, investigated by modern methods, is reviewed. The clinical picture of progressive neurological deficit, and/or intellectual impairment, did not differ greatly from that of younger patients, but the manifestations of raised intracranial pressure (headache and papilloedema) were much less common in the elderly. Intermittency of symptoms appeared to be a relatively common phenomenon with meningiomas, occurring in four of 12 symptomatic cases. Operative treatment, for removal of meningiomas or relief of obstructive hydrocephalus, produced improvement in almost all cases, with a low morbidity and mortality. High-dose steroid therapy produced substantial, if temporary, benefit in 51% of hemisphere tumours.


Mouse iPSC generated with porcine reprogramming factors as a model for studying the effects of non-silenced heterologous transgenes on pluripotency.
Mouse somatic cells can be reprogrammed to pluripotency by the ectopic expression of four pluripotency transcription factors, Oct4, Sox2, cmyc, and Klf4. Usually, silencing of the exogenous reprogramming factors is considered to be essential for complete reprogramming and differentiation. In the vast majority of studies, murine pluripotency transcription factor sequences have been used for the reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSC). The effectiveness of xenogeneic transcription factors in miPSC generation has not yet been investigated in detail. Here, we evaluated transposon-based vectors with four porcine pluripotency factors for their ability to reprogram mouse fetal fibroblasts (MEFs) harboring an Oct4-EGFP reporter construct to pluripotency. Additionally, we examined the effects of the non-silenced heterologous transgenes on the expression levels of key endogenous pluripotency markers and the differentiation capacities of the miPSC. Within 8 days of transfection with porcine reprogramming transcription factors the MEFs acquired typical compact miPSC morphology and upregulated expression of endogenous Oct4 and other critical pluripotency genes. Consequently, the transgenes under the control of the TetO promoter became silenced, while the CAG-controlled constructs were expressed throughout the period of culture. Despite the continuous transgene expression, the CAG-miPSC showed normal morphology and were capable of differentiation into the three primary germ layers in vitro and in vivo. However, the expression levels of important endogenous pluripotency markers, Klf4, c-myc, Rex1, and Utf1, were significantly lower in CAG-miPSC compared with TetO-miPSC with silenced reprogramming cassettes. Surprisingly, the endogenous Oct4 and Sox2 expression levels were not affected by the residual transgene expression. Our results suggest that porcine reprogramming transcription factors are suitable for production of miPSC, but silencing of the heterologous transgenes may be necessary for complete reprogramming to pluripotency.


Understanding the Barriers to and Facilitators of Anxiety Management in Residents of Long-Term Care.
Older adults, 65 years of age and older, living in long-term care (LTC) commonly experience anxiety. This study aimed to understand care providers' perspectives on the barriers to and facilitators of managing anxiety in residents of LTC. Ten semi-structured interviews with care providers in LTC were completed. Framework analysis methods were used to code, thematically analyze, designate codes as barriers or facilitators, and map the codes to the Theoretical Domains Framework. Themes were categorized as acting at the resident, provider, or system level, and were labelled as either barriers to or facilitators of anxiety care. Key barriers to anxiety care at each level were resident cognitive impairment or co-morbidities; lack of staff education, staff treatment uptake and implementation; as well as the care delivery environment and access to resources. There is a need to prioritize measurement-based care for anxiety, have increased access to non-pharmacological treatments, and have a care delivery environment that supports anxiety management to improve the care for anxiety that is delivered to residents.


[Suitability of the Weidemann test for galactose in mass screening (author's transl)].
With slight practical modification, especially in the preparation of blood samples on filter paper in place of liquid blood samples, it was possible to adapt the determination of galactose dehydrogenase (Weidemann, G. (1971), this Journal 9,527) to mass screening. The technique is described, and the first results are briefly discussed and compared with those obtained over the years in our screening program with proven the Guthrie test (1): The dehydrogenase test is much quicker and shows a higher substrate specificity than the Guthrie test (duration 2 hours compared with 44 hours; false positive results of 16.87 mmol/l galactose or higher 1:42231 compared with 1:3519). It is, however, less sensitive (16.87 mmol/l compared with 1.69 mmol/l galactose), so that a combination of both tests would seem appropriate for the mass screening of new borns.


Role of the renin-angiotensin-aldosterone system in diastolic heart failure: potential for pharmacologic intervention.
Congestive heart failure (CHF) is a major public health problem that results in tremendous economic burden. Diastolic heart failure (DHF) forms an important subset with increasing incidence and prevalence. There are widely variable estimates of the prevalence, ranging from 13% to 74% of all CHF presentations, and this is predominantly a result of a lack of uniform criteria for establishing a diagnosis. New developments in management of DHF have lagged behind those for systolic heart failure (SHF), for which numerous new therapeutic and device strategies have been instituted. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of both SHF as well as DHF. The beneficial role of ACE inhibitors as well as aldosterone antagonists in SHF has been well established. Because of its unique role of the RAAS in establishing fibrosis at a molecular level, RAAS blockade provides an opportunity to expand the therapeutic options for DHF. Thus far, in patients with primary DHF only the angiotensin receptor type 1 antagonist candesartan has been reported to decrease morbidity and probably mortality. Large, ongoing randomized trials including TOPCAT (Trial of Aldosterone Antagonist Therapy in Adults with Preserved Ejection Fraction Congestive Heart) and the I-PRESERVE (Irbesartan in Heart Failure with Preserved Systolic Function) are currently underway to establish the role of aldosterone antagonists in patients with DHF.


Evaluating the Perceived Efficacy of Randomized Security Measures at Airports.
Both the increase in traveler numbers and the heightened threat posed by terrorism in recent years represent significant challenges to airport security measures. To ensure that a high level of security is maintained, randomized security checks have been proposed as a promising alternative to traditional security approaches. The use of randomized checks means that only a specific number of people are selected for security screening. However, the likely effects of such a change in security procedures on travelers' security perceptions and on the deterrence of criminal activities remain unclear. Thus, the present study examines how varying the percentage of people screened during security checks influences people's security perceptions. In two online experiments, the participants were asked to imagine that they sought to smuggle an explosive dummy past an airport security check. The only information provided was the number of people screened during security checks, which was manipulated between-subjects in the first experiment and within-subjects in the second experiment. The participants then had to rate their security perception (i.e., the perceived likelihood of successfully smuggling the explosive dummy). The findings show that people perceive traditional security checks to be safer than randomized checks, irrespective of whether 90% or 30% of people are screened. Hence, if randomized security checks would indeed be implemented, it would automatically lead to a decreased perception of security. Furthermore, this decreased security perception might lead to an actual reduction in security, as the deterrence of criminal activities could also be reduced.


Cancer: the role of extracellular disease.
Invasive carcinoma originates from the epithelial cells lining the lumen of an organ. It is often preceded by metaplasia, dysplasia or carcinoma in situ. The purpose of this review is to suggest that this disease of the epithelium may be, in part, the result of underlying tissue-based disorganization. Human cancer is frequently associated with pre-existing tissue disease. For example, hepatocellular carcinoma usually occurs in patients with a macronodular cirrhotic liver. Most lung cancers arise among patients with chronic lung disease (bronchitis, emphysema, and chronic infection). Mechanical forces appear to play a major role in regulating normal and cancer cell growth. The loss of cell polarity by neoplastic cells, coupled to an otherwise normal growth rate is enough to explain the cancer star-shaped pattern. By changing the plane of cell division, tumor cells may escape physical constraints from surrounding cells and divide. Loss of cell polarity and the resulting cell proliferation appears to be a consequence of either tissue-based disorganization (chronic inflammation, fibrosis) or of direct carcinogenic insult. The multiple mutations frequently described in cancer may be, in part, secondary to physical stress and not primary events. Several animal and clinical trials have shown that tissue disruption (i.e. radiation-induced fibrosis or liver cirrhosis) can be successfully treated. It is possible that treatment targeted at tissue disruption would delay or reduce cancer incidence regardless of the precise biological mechanism of carcinogenesis.


Biochar Application Mitigates the Effect of Heat Stress on Rice (Oryza sativa L.) by Regulating the Root-Zone Environment.
Coping with global warming by developing effective agricultural strategies is critical to global rice (Oryza sativa L.) production and food security. In 2020, we observed that the effect of heat stress on rice plants was mitigated by biochar application (40 g kg-1 soil) in a pot experiment with six consecutive days (6-11 days after transplanting) of daily mean temperatures beyond the critical high temperature (33°C) for tillering in rice. To further determine the eco-physiological processes underlying the effect of biochar on resistance to heat stress in rice plants, we compared root-zone soil properties as well as some plant growth and physiological traits related to nitrogen (N) utilization between rice plants grown with and without biochar in the pot experiment. The results showed that the application of biochar improved the root-zone environment of rice plants by reducing soil bulk density, increasing soil organic matter content, and altering soil bacterial community structure by increasing the ratio of Proteobacteria to Acidobacteria, for example. As a consequence, root morphology, architecture, and physiological traits, such as N assimilation and transport proteins, as well as shoot N uptake and utilization (e.g., photosystems I and II proteins), were improved or up-modulated, while the heat-shock and related proteins in roots and leaves were down-modulated in rice plants grown with biochar compared to those without biochar. These results not only expand our understanding of the basic eco-physiological mechanisms controlling increased heat-stress tolerance in rice plants by the application of biochar, but also imply that improving the root-zone environment by optimizing management practices is an effective strategy to mitigate heat stress effects on rice production.


Bioremediation concepts for treatment of dye containing wastewater: a review.
Synthetic dyes are extensively used in wide range of industries amongst which textile processing industries are the major consumers. Large amounts of dyes are lost in wastewaters of these industries during dyeing and subsequent washing steps of textiles. These dyes are resistant to de gradation by conventional wastewater treatment plants and are released into environment untreated thus causing pollution of surface and ground waters in the areas of the world harboring such industries. Presence of color in wastewaters has become major environmental concern and stringent discharge standards are being enforced on release of colored wastewaters in environment. The seriousness of the problem is apparent from the magnitude of the research done in this field in last decade. Increasing number of microorganisms are being described for their ability to decolorize and degrade artificial dyes and novel bioremediation approaches for treatment dye bearing wastewaters are being worked out. In this review we have investigated potential microbial processes for developing feasible remediation technology to combat environmental pollution due to dye bearing wastewaters.


The effect of a maternal history of childhood abuse on adrenocortical attunement in mothers and their toddlers.
We investigated circadian mother-child adrenocortical attunement in the context of a maternal history of childhood abuse (HoA). Mothers were screened after birth using the Childhood Trauma Questionnaire. Women reporting moderate or severe abuse formed the HoA group (n = 37; HoAG) and were compared with a non-maltreated comparison group (n = 45; CG). Three years later, cortisol awakening response (CAR) and diurnal slope (DSL) were assessed. Mother-child interaction was coded using the Emotional Availability Scales at 12 months of age. For the CAR, we found adrenocortical attunement only in the HoAG (2-way interaction: p = .004), particularly if mothers scored low on structuring (3-way interaction: p = .042) and children scored low on responsiveness (3-way interaction: p = .044). DSL-attunement was dependent on maternal sensitivity (3-way interaction: p = .012) and child involvement (3-way interaction: p = .012). In the context of a maternal HoA, it seems possible for mother-child-dyads to show less optimal interactional quality but be stronger attuned to each other biologically.


Chronic Mild Stress Causes Bone Loss via an Osteoblast-Specific Glucocorticoid-Dependent Mechanism.
Chronic stress and depression are associated with alterations in the hypothalamic-pituitary-adrenal signaling cascade and considered a risk factor for bone loss and fractures. However, the mechanisms underlying the association between stress and poor bone health are unclear. Using a transgenic (tg) mouse model in which glucocorticoid signaling is selectively disrupted in mature osteoblasts and osteocytes [11β-hydroxysteroid-dehydrogenase type 2 (HSD2)OB-tg mice], the present study examines the impact of chronic stress on skeletal metabolism and structure. Eight-week-old male and female HSD2OB-tg mice and their wild-type (WT) littermates were exposed to chronic mild stress (CMS) for the duration of 4 weeks. At the endpoint, L3 vertebrae and tibiae were analyzed by micro-computed tomography and histomorphometry, and bone turnover was measured biochemically. Compared with nonstressed controls, exposure to CMS caused an approximately threefold increase in serum corticosterone concentrations in WT and HSD2OB-tg mice of both genders. Compared with controls, CMS resulted in loss of vertebral trabecular bone mass in male WT mice but not in male HSD2OB-tg littermates. Furthermore, both tibial cortical area and area fraction were reduced in stressed WT but not in stressed HSD2OB-tg male mice. Osteoclast activity and bone resorption marker were increased in WT males following CMS, features absent in HSD2OB-tg males. Interestingly, CMS had little effect on vertebral and long-bone structural parameters in female mice. We conclude that in male mice, bone loss during CMS is mediated via enhanced glucocorticoid signaling in osteoblasts (and osteocytes) and subsequent activation of osteoclasts. Female mice appear resistant to the skeletal effects of CMS.


Microcystins-Loaded Aged Nanoplastics Provoke a Metabolic Shift in Human Liver Cells.
Studies concerning the toxicity of pollutant-loaded nanoplastics (NPs) toward humans are still in their infancy. Here, we evaluated the adsorption of microcystins (MCs) by pristine and aged polystyrene nanoplastics (PSNPs), prepared MCs-loaded aged PSNPS (1, 5, 10, 15, and 19 μg/mg), and systematically mapped the key molecular changes induced by aged and MCs-loaded PSNPs to human hepatoblastoma (HepG2) cells. According to the results, MC-LR adsorption is increased 2.64-fold by aging, and PSNP accumulation is detected in HepG2 cells. The cytotoxicity of the MC-LR-loaded aged PSNPs showed a positive relationship with the MC-LR amount, as the cell viability in the 19 μg/mg loading treatment (aPS-MC19) was 10.84% lower than aged PSNPs; meanwhile, more severe oxidative damage was observed. Primary approaches involved stressing the endoplasmic reticulum and reducing protein synthesis that the aged PSNPs posed for HepG2 cells, while the aggravated cytotoxicity in aPS-MC19 treatment was a combined result of the metabolic energy disorder, oxidative damage, endoplasmic reticulum stress, and downregulation of the MC-LR target protein. Our results confirm that the aged PSNPs could bring more MC-LR into the HepG2 cells, significantly interfere with biological processes, and provide new insight into deciphering the risk of NPs to humans.


Sperm acrosome antigen-1. Specific tissue distribution of immunoreactivity in a teleost fish, the swordtail ( Xiphophorus helleri).
The acrosome reaction is a fundamental requirement for mammalian fertilization. Its exact molecular mechanisms and cellular elements are still poorly understood. We have detected an acrosomal sperm antigen, SAA-1, by monoclonal antibodies directed against SAA-1, that appears to be critically involved in the regulation of the acrosome reaction. SAA-1 is conserved within a broad range of mammalian species, emphasizing its important role in mammalian reproduction. Here we demonstrate that SAA-1 is immunohistochemically detectable in a nonmammalian vertebrate whose sperm do not possess an acrosome. In the swordtail, a live-bearing teleost with special reproductive tactics, we were able to demonstrate immunoreactivity of sperm heads of spermatids and mature sperm in the testis using monoclonal antibodies against SAA-1. Due to the cystic spermatogenesis with synchronous sperm maturation, immunoreactive maturational stages could be clearly identified. Stored immunoreactive sperm were also identified in spermathecal tissue of the female genital tract. Interestingly, immunoreactivity was furthermore detected in defined cells of the compounded endocrine organs pituitary and endocrine pancreas. All these different cell systems are involved in paracrine regulation and exhibit exocytotic properties. The possible nature of SAA-1 is discussed. Additionally, some new aspects of the morphologic composition of the swordtail pituitary are described.


Silicon-phthalocyanine-cored fullerene dendrimers: synthesis and prolonged charge-separated states with dendrimer generations.
Silicon-phthalocyanine-cored fullerodendrimers with up to eight fullerene substituents (SiPc-n C(60); n=2, 4, and 8) have been synthesized. Photophysical properties of newly synthesized SiPc-n C(60) have been investigated by time-resolved fluorescence and transient absorption analysis with pulsed laser light. Laser photolysis measurements suggest the occurrence of a charge-separation process from (1)SiPc* to the C(60) subunits. The nanosecond transient absorption spectra in the near-IR region indicate that the lifetimes of the formed radical ion pairs are prolonged on the order of SiPc-8 C(60)>SiPc-4 C(60)>SiPc-2 C(60), which may be related to the electron migration among the C(60) subunits. The usefulness of SiPc-n C(60) as light-harvesting systems, evaluated as a ratio of the rates of charge recombination to those of charge separation, increases markedly with the dendrimer generation.


The experimental chemotherapy of leishmaniasis. II. The activity in tissue culture of some antiparasitic and antimicrobial compounds in clinical use.
A variety of compounds used in the treatment of parasitic or bacterial infections in man, including leishmaniasis itself, were examined for their activity against three lines of Leishmania in tissue culture. The organisms used were L. mexicana mexicana, L. tropical major and L. donovani; they were grown in dog sarcoma and hamster peritoneal exudate cell lines. Leishmanicidal activity was observed in a number of compounds currently in clinical use for the treatment of one or other form of leishmaniasis. Cycloguanil, nifurtimox, amphotericin B and monomycin were effective but pentamidine showed poor activity. In each case marked differences were observed in the level of response in the different parasite lines. Organic antimonials were most active when anmastigotes were exposed to them prior to entry of the parasites into host cells. This suggests that such compounds may exert an effect on amastigotes during their brief extracellular transit from one host cell to another in vivo. A number of antimalarials showed good to moderate leishmanicidal action, particularly against L. mexicana and L.t. major. Several schistosomicidal agents also possessed leishmanicidal properties. The commonly used broad spectrum antibiotics showed little if any activity. In discusssion a comparison is drawn between data published on the action of some of these drugs against L.t. major in mice and our observations with the same strain and L. mexicana in tissue culture. A remarkably good agreement is found for most of the compounds examined. General agreement is also noted between these data and reports of clinical trials although it is not possible to draw too many conclusions because of the failure in most clinical studies to make an accurate identification of the causative Leishmania. It is concluded that, although the tissue culture model is not to be considered as ideal and can probably be improved, data obtained by its use do bear relevance to the action compounds in vivo, and the model may be use in the screening of drugs for leishmanicidal activity.


Hardware simulator for optical correlation spectroscopy with Gaussian statistics and arbitrary correlation functions.
We present a new hardware simulator (HS) for characterization, testing and benchmarking of digital correlators used in various optical correlation spectroscopy experiments where the photon statistics is Gaussian and the corresponding time correlation function can have any arbitrary shape. Starting from the HS developed in [Rev. Sci. Instrum. 74, 4273 (2003)], and using the same I/O board (PCI-6534 National Instrument) mounted on a modern PC (Intel Core i7-CPU, 3.07GHz, 12GB RAM), we have realized an instrument capable of delivering continuous streams of TTL pulses over two channels, with a time resolution of Δt = 50ns, up to a maximum count rate of 〈I〉 ∼ 5MHz. Pulse streams, typically detected in dynamic light scattering and diffuse correlation spectroscopy experiments were generated and measured with a commercial hardware correlator obtaining measured correlation functions that match accurately the expected ones.


Matrix metalloproteinase-2 matrix metalloproteinase-9 and inducible nitric oxide synthase in oral leukoplakia: immunohistochemistry and RT-PCR analysis.
Oral leukoplakia is the most common and potentially malignant disorder of the oral mucosa. The definition of leukoplakia given by the World Health Organization is ?a white plaque that cannot be characterized either from a clinical or from a histopathological point of view?, thus the diagnosis of leukoplakia is based on the exclusion of other lesions of the oral mucosa. We believe it is necessary to identify molecular and immunohistochemical parameters that can contribute to discriminating between the different leukoplakia clinical subtypes coded by the epidemiology. In the present work we show the preliminary results of this research project. We investigated the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS) in a verrucous proliferative leukoplakia sample. By immunohistochemistry we detected the presence of all the three proteins both in the leukoplakia samples and in healthy oral mucosa, while the reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed in both samples only the expression of MMP-2 and MMP-9 but not iNOS.


[Construction of special reporter to detect DNA methylation regulatory activity in FCER1G gene promoter through patch-methylation].
To construct a special luciferase reporter to detect DNA methylation regulatory activity in FCER1G gene promoter regulatory element. We constructed special full and mock methylated FCER1G gene promoter regulatory luciferase reporters by patch-methylation, and detected DNA methylation regulatory activity by comparing the luciferase activity of full-methylated luciferase reporters with mock-methylated reporters. We successfully constructed the full and mock methylated FCER1G gene promoter regulatory luciferase reporters. The ratio of luciferase activity between the full methylated and the mock methylated was (0.36±0.07):1 (P<0.001). FCER1G promoter activity is methylation-sensitive and is regulated by DNA methylation.