A truncating mutation in the laminin-332α chain highlights the role of the LG45 proteolytic domain in regulating keratinocyte adhesion and migration.
Altered function of laminin-332 (α3β3γ2) consequent to mutations in the LAMA3, LAMB3 and LAMC2 genes causes junctional epidermolysis bullosa non-Herlitz (JEB-nH). JEB-nH patients suffer from skin blistering and have an increased risk of developing aggressive skin carcinomas in adulthood. Laminin-332 is proteolytically processed and its extracellular mature form lacks the α3 chain C-terminal globules 4 and 5 (LG45). The LG45 tandem has cell adhesion and protumorigenic properties. However, mutations that affect this domain are very rare and their functional effects in patients have not been explored to date. To characterize molecularly an adult patient with JEB-nH and altered laminin-332 expression presenting multiple skin carcinomas, and to analyse LG45-mediated biological functions using keratinocytes from the patient. A mutational search in laminin-332 genes was performed by hetero-duplex analysis. LAMA3 mRNA and laminin-332 protein levels in patient keratinocytes were investigated by real-time reverse transcriptase polymerase chain reaction and radioimmunoprecipitation assay, respectively. Keratinocyte migration was examined by scratch and Boyden chamber assays. We identified a homozygous LAMA3 mutation, p.Leu1648TrpfsX32, which truncates the last 45 amino acids of the carboxyl terminal LG5 subdomain. Gene expression studies revealed that the mutant transcripts were stable and even increased, precursor laminin-332 molecules were retained intracellularly and the amount of mature extracellular heterotrimers was reduced to about 50%. Finally, the patient's keratinocytes migrated faster than normal keratinocytes. Structural disruption of LG5 highlights the critical functions of the LG45 proteolytic region in precursor laminin-332 secretion and keratinocyte adhesion and migration. Perturbation of LG45 function might explain the non-aggressive behaviour of carcinomas in this patient.


[The role of the clinical microbiology laboratory in the past].
Over the past 150 years, since Koch first isolated the tubercle bacillus, clinical microbiologists have used culturing techniques to demonstrate of the presence of pathogenic microorganisms associated with infectious diseases in clinical specimens. The development of medicine and chemotherapy and the improvement of sanitary conditions resulted in a marked decrease in infectious diseases. In stead of infections due to virulent pathogens, opportunistic infections in the compromised hosts by non-virulent or weakly virulent bacteria have been on the rise. As a result, determining the pathogenicity of an isolated bacteria becomes important. The past two decades have seen extensive efforts to exploit the potential of automation in clinical microbiology and to develop increasingly rapid procedures. New technology, such as molecular genetics, has also been introduced into clinical microbiology. For more correct and precise diagnoses of infectious diseases, the clinical microbiology laboratory should be enlarged as an "Infectious Disease Laboratory" to include an extended work on not only the detection of pathogens from the specimens of infectious disease, but also serodiagnostic tests and immunological tests of hosts. The "Infectious Disease Laboratory" would also play a key role in the control of nosocomial infection working with the infection control committee and infectious disease clinicians.


An extension of stochastic hierarchy equations of motion for the equilibrium correlation functions.
A traditional stochastic hierarchy equations of motion method is extended into the correlated real-time and imaginary-time propagations, in this paper, for its applications in calculating the equilibrium correlation functions. The central idea is based on a combined employment of stochastic unravelling and hierarchical techniques for the temperature-dependent and temperature-free parts of the influence functional, respectively, in the path integral formalism of the open quantum systems coupled to a harmonic bath. The feasibility and validity of the proposed method are justified in the emission spectra of homodimer compared to those obtained through the deterministic hierarchy equations of motion. Besides, it is interesting to find that the complex noises generated from a small portion of real-time and imaginary-time cross terms can be safely dropped to produce the stable and accurate position and flux correlation functions in a broad parameter regime.


Are anticoagulant independent mechanical valves within reach-fast prototype fabrication and in vitro testing of innovative bi-leaflet valve models.
Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence. Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves. Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0). Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring the anti-coagulation independent mechanical valve within reach.


Evaluation of Healthcare Use and Clinical Outcomes of Alvimopan in Patients Undergoing Bowel Resection: A Propensity Score-Matched Analysis.
Postoperative ileus is a significant complication after bowel resection surgeries. Alvimopan is the only US Food and Drug Administration-approved therapy for accelerating the return of bowel function after large- and small-bowel resection. The purpose of this study was to estimate the healthcare use and in-hospital morbidities associated with on-label use of alvimopan in patients undergoing bowel resection surgeries. A retrospective observational propensity-matched cohort study was conducted using a large hospital administrative database. The study included inpatient postsurgical patients. Patients aged ≥18 years undergoing a primary large or small segmental bowel resection with discharge dates between January 2010 and December 2014 were included. Patients receiving 2 to 15 doses of alvimopan were defined as the treatment cohort, and those without any alvimopan use were included as control subjects. The primary outcome was postoperative length of stay. Secondary outcomes included postoperative in-hospital morbidities, inpatient mortality, intensive care unit length of stay, discharge disposition, and 30-day readmission. Each propensity-score matched cohort included 18,559 patients. The mean (±SD) postoperative length of stay was 4.62 ± 2.45 days in alvimopan-treated patients compared with 5.24 ± 3.35 days in control subjects (p < 0.001). Alvimopan-treated patients had lower rates of postoperative GI complication (12.15% vs 16.50%; p < 0.001). The rates of urinary tract infections; other postoperative infections; and cardiovascular, pulmonary, thromboembolic, and cerebrovascular events were also lower compared with the control subjects. The study was limited by its inability to generalize to the US population, because the database included a convenience sample of hospital discharges. The identification of patients undergoing bowel resection and their clinical conditions relied on the accuracy and completeness of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure coding. There may be a confounding effect by the use of enhanced recovery pathways associated with the use of alvimopan. The use of alvimopan was associated with a reduction of 0.62 days in postsurgery length of stay and lower rates of postoperative GI complications, infections, and other in-hospital morbidities. See Video Abstract at http://links.lww.com/DCR/A703.


[Stem cells to regenerate cardiac tissue in heart failure].
Myocardial regeneration is one of the most promising therapeutic strategies for heart failure patients. Many experimental studies have demonstrated that different types of stem cell can differentiate into myocardial cells and tissues necessary for regeneration of the damaged myocardium, while studies in experimental animals suggest that muscle (myoblast), bone marrow (mesenchymal, endothelial or hematopoietic progenitors) and even heart cells can help to improve heart contractility in vivo. These findings have led several groups to undertake studies in patients with myocardial infarction. However, the use of cellular therapy in clinical trials is not without controversy, mainly related with the need for better knowledge before these therapeutic strategies are used in clinical practice. Although significant enhancement of our knowledge of the processes involved is fundamental, we do not consider it unreasonable to initiate clinical trials in which specific questions are posed, whose answers will allow us to make further progress.


Initial peri- and postoperative antibiotic treatment of infected nonunions: results from 212 consecutive patients after mean follow-up of 34 months.
Infected nonunions of the long bones belong to the most feared complications in the field of orthopedic and trauma surgery. Optimal antibiotic therapy should start early with the first revision surgery. Therefore, the aim of this study was to evaluate our peri- and postoperative antibiotic regime in context with the microbial spectrum and antibiotic resistances of patients with infected nonunions and to assess the possible impact on healing rates. We included all patients with first revision surgery during 2010-2015 due to nonunion of long bones with a clinical history of infection treated with radical debridement, local application of a gentamicin-impregnated bone cement, and systemic cefuroxime. Mean follow-up was 34.2 months. Data collection was performed retrospectively using a computerized databank with information about microbial species from intraoperatively acquired tissue samples and respective antibiograms. Bone fusion rates were evaluated based on findings of the latest X-rays and computed tomography scans. Two hundred and twelve patients with nonunion and history of infection were selected; 171 patients had positive intraoperative microbial evidence of infection. Bacterial testing was mostly positive in fractures of the tibia (47.4%) and the femur (27.5%). Coagulase-negative Staphylococcus spp. were the most frequently detected (44.4%) followed by mixed infections (18.7%) and Staphylococcus aureus (10.5%). Antibiograms revealed that 62.6% of our cases were cefuroxime sensitive; 87.7% were gentamicin sensitive. Only 10.5% showed resistance to both cefuroxime and gentamicin. There was no statistically significant difference of fusion rates between patients with different microbial species or different antibiograms. Our data suggest that besides the high variety of different detected species, initial antibiotic treatment with a combination of systemic cefuroxime and local gentamicin-loaded bone cement is effective and in almost 90% the later determined microbial infection was sensitive to this treatment. Therefore, we recommend initial treatment according to this algorithm until specific antibiograms are available from intraoperatively acquired tissue samples.


Deduced primary structure of the alpha subunit of the GTP-binding stimulatory protein of adenylate cyclase.
A bovine adrenal cDNA clone encoding the entire alpha subunit of the GTP-binding regulatory protein that stimulates adenylate cyclase (Gs) was isolated and sequenced. This cDNA directed the synthesis of the larger, 52-kDa form of the polypeptide in COS cells, even though the clone appeared to encode a 46-kDa protein. Comparison of the deduced amino acid sequence of Gs alpha with the alpha subunit of another G protein, transducin, revealed striking homologies.


Intrinsic surface dipole in topological insulators.
We calculate the local density of states of two prototypical topological insulators (Bi2Se3 and Bi2Te2Se) as a function of distance from the surface within density functional theory. We find that, in the absence of disorder or doping, there is a 2 nm thick surface dipole the origin of which is the occupation of the topological surface states above the Dirac point. As a consequence, the bottom of the conduction band is bent upward by about 75 meV near the surface, and there is a hump-like feature associated with the top of the valence band. We expect that band bending will occur in all pristine topological insulators as long as the Fermi level does not cross the Dirac point. Our results show that topological insulators are intrinsic Schottky barrier solar cells.


Rhodium-Catalyzed Direct Bis-cyanation of Arylimidazo[1,2-α]pyridine via Double C-H Activation.
An efficient Cp*Rh(III)-catalyzed selective bis-cyanation of arylimidazo[1,2-α]pyridines with N-cyano-N-phenyl-p-methylbenzenesulfonamide via N-directed ortho double C-H activation has been developed. The reaction proceeds with broad functional group tolerance to furnish various cyanated imidazopyridines in high yields. The current methodology exhibits unique characteristics, including high bis-cyanation selectivity, operational convenience, and gram-scale production.


Patient-related factors influencing patency of autogenous brachiocephalic haemodialysis fistulas.
The objective of this study was to analyse the outcome of autogenous brachiocephalic fistula for dialysis purposes and to determine modifiable and non-modifiable patient-related factors of influence on the patency of a newly created fistula. A single-centre retrospective cohort study with the aim of determining patient-related factors of influence on primary failure, primary, primary assisted and secondary patency of autogenous brachiocephalic fistulas. Seventeen patient-related variables were determined by means of univariate analysis, variables reaching significance were then entered in a multivariate Cox-regression model. Between October 2005-October 2015, 231 autogenous brachiocephalic fistulas were created in 228 patients. Mean age was 61.3 years (20.3-88.2 years). Patency was calculated using Kaplan-Meier analysis. Primary failure occurred in 38 out of 231 created fistulas (16.5%). The primary, primary assisted and secondary patency rates at six months were 78 ± 3%, 93 ± 2%, and 95 ± 1%, respectively. At 12 months, they were 63 ± 3%, 89 ± 2%, and 92 ± 2%, and at 24 months 47 ± 4%, 84 ± 3%, and 89 ± 2%. The non-modifiable factors, diabetes mellitus and mean cephalic vein diameter were identified as a predictor for failure influencing primary and secondary patency. The preoperative use of anticoagulation was identified as a modifiable factor for failure. This study identified several non-modifiable and modifiable factors of interest to the clinician deciding on which type of haemodialysis fistula is most suitable for an individual patient. Meticulous preoperative work-up, a surveillance programme, and a dedicated multidisciplinary team can be of great importance in achieving better patency rates.


Hepatic glutathione homeostasis in the rat: efflux accounts for glutathione turnover.
Hepatic glutathione turnover and the efflux of glutathione from the liver into bile and blood were measured in male Sprague-Dawley rats in vivo. In fed rats the efflux of glutathione into blood, calculated from the hepatic arteriovenous concentration gradient and hepatic blood flow, amounted to 12.4 +/- 1.4 nmoles min X gm liver. Together with the excretion of glutathione into bile (3.4 +/- 0.4 nmoles per min X gm liver) total efflux accounted for the hepatic turnover of glutathione of 15.2 +/- 0.9 nmoles per min X gm liver. Fasting animals for 48 hr markedly increased hepatic glutathione turnover to 26.4 +/- 1.2 nmoles per min X gm liver. Increased efflux into blood rather than increased intrahepatic catabolism accounted for this increased turnover. The systemic clearance of glutathione was 3.22 +/- 0.51 ml per min X 100 gm body weight. The efflux of glutathione from liver therefore was calculated to contribute over 90% of total glutathione inflow into the circulation, as determined from the clearance and the arterial concentration of glutathione. Thus, the liver is the major source of plasma glutathione, and turnover of hepatic glutathione in the basal state is accounted for almost entirely by efflux of glutathione from the liver. During fasting, the plasma clearance of exogenous glutathione increased to 5.32 +/- 0.35 ml per min X 100 gm body weight, and the utilization of methionine for glutathione synthesis increased markedly. The increased extrahepatic catabolism during fasting results in a decrease in plasma glutathione, which in turn may account for the observed increase in sinusoidal glutathione efflux with concomitant stimulation of the rate of hepatic glutathione turnover and of synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Late-Stage 18F/19F Isotopic Exchange for the Synthesis of 18F-Labeled Sulfamoyl Fluorides.
Synthesis of sulfamoyl [18F]fluorides has been a challenging topic owing to the inefficient nucleophilic radiofluorination of sulfamoyl derivatives. Herein, we report an 18F/19F isotopic exchange approach to synthesize various sulfamoyl [18F]fluorides, otherwise inaccessible via direct synthesis from amines, with high radiochemical yields up to 97% (30 examples). This late-stage labeling protocol offers an efficient route to yield functionalized molecules by diversifying the chemical library possessing sulfamoyl functionalities through nucleophilic 18F incorporation within nitrogen-containing sulfur(VI) frameworks.


Calculation of power and field of view of keratoprostheses.
To demonstrate a mathematical algorithm for calculating the refractive power of keratoprostheses and to estimate vignetting effects. A paraxial calculation scheme based on vergence transformation is developed for determination of the front surface radius or front surface refractive power of a Boston type I or II keratoprosthesis based on the design data of the manufacturer. A concept for derivation of lateral magnification (ratio of image size to slope of the incident ray) is presented based on 2 × 2 matrix representation of the eye. For estimation of vignetting effects, numerical ray tracing was used and the maximum half field angle and half luminance half field angle was extracted. Simulation calculations were performed in MATLAB. The front surface radius or refractive power is given in explicit form as a function of axial length, target refraction, as well as the principal design data of the keratoprosthesis such as posterior refractive power, length, or refractive index. With variation of the back surface radius it was shown that lateral magnification can be modulated e.g. to match the magnification of the fellow eye. The Boston type I does not restrict the field angle substantially, whereas type II shows significant vignetting effects. We present a strategy on the calculation of keratoprostheses and variation of the design (e.g. back surface curvature) to help to avoid aniseikonia in case of binocular vision (e.g. one phakic eye and one with keratoprosthesis).


Primitive reflex profile: a quantitation of primitive reflexes in infancy.
This report describes quantitative standardization data on nine primitive reflexes for a cohort of 381 normal infants evaluated longitudinally at each visit between birth and two years of age. Normality was confirmed by the use of the Bayley Scales of Infant Development at one year of age. The standardization of this new examination technique complements the traditional infant neurological examination and may allow primitive reflexes to become a useful adjunct to the prediction of motor disability in early infancy.


The evolution of targeted cannibalism and cannibal-induced defenses in invasive populations of cane toads.
Biotic conflict can create evolutionary arms races, in which innovation in one group increases selective pressure on another, such that organisms must constantly adapt to maintain the same level of fitness. In some cases, this process is driven by conflict among members of the same species. Intraspecific conflict can be an especially important selective force in high-density invasive populations, which may favor the evolution of strategies for outcompeting or eliminating conspecifics. Cannibalism is one such strategy; by killing and consuming their intraspecific competitors, cannibals enhance their own performance. Cannibalistic behaviors may therefore be favored in invasive populations. Here, we show that cane toad tadpoles (Rhinella marina) from invasive Australian populations have evolved an increased propensity to cannibalize younger conspecifics as well as a unique adaptation to cannibalism-a strong attraction to vulnerable hatchlings-that is absent in the native range. In response, vulnerable conspecifics from invasive populations have evolved both stronger constitutive defenses and greater cannibal-induced plastic responses than their native range counterparts (i.e., rapid prefeeding development and inducible developmental acceleration). These inducible defenses are costly, incurring performance reductions during the subsequent life stage, explaining why plasticity is limited in native populations where hatchlings are not targeted by cannibalistic tadpoles. These results demonstrate the importance of intraspecific conflict in driving rapid evolution, highlight how plasticity can facilitate adaptation following shifts in selective pressure, and show that evolutionary processes can produce mechanisms that regulate invasive populations.


Doping control in sports--a perspective from the 1996 Olympic Games.
Doping-control (DC) procedures, particularly as used at the 1996 Olympic Games, are described, and the role of pharmacists in DC is discussed. DC procedures must be strict and precisely followed to avoid contamination of samples, the appearance of bias, and breaches in security and confidentiality. The process of selecting athletes for testing can be random, nonrandom, or a combination of the two. Escorts are used to notify athletes of their selection, verify their identity, and accompany them to the DC station. When urine specimens are obtained for DC, the voiding process must be directly observed. The specimen is checked for pH and specific gravity and then processed for shipping to a laboratory to be analyzed for banned substances. Medication histories are also obtained, giving athletes the opportunity to declare any substance that has been taken for legitimate medical purposes. Laboratory analysis involves screening and confirmation phases. During the Atlanta Games, roughly 50 pharmacists participated in the DC program as escorts or technical officers. It is logical to involve pharmacists in DC programs because they can develop and conduct drug-testing protocols; educate athletes, coaches, and trainers about drug use and abuse; and help ensure the safe and effective use of medications. Sophisticated doping-control procedures have been developed for athletic competitions, and pharmacists have much to offer DC programs.


Production of 6-keto-PG F1 alpha in hyperstimulated cycles: in vivo and in vitro studies.
Prostacyclin (PG12), a potent vasodilator, is believed to be involved in increasing permeability within the wall of the preovulatory follicle. In ovarian hyperstimulation syndrome (OHSS), increased vascular permeability has been shown to lead to massive fluid accumulation in ovarian cysts and the peritoneal cavity. The objective of the in vitro and in vivo studies reported herein was to examine the production of 6-keto PGF1 alpha (a breakdown metabolite of PG12) during the luteal phase of women who develop OHSS, as well as the capacity of human granulosa luteal cells (GLC) obtained from stimulated in vitro fertilization (IVF) cycles to synthesize PGF1 alpha in vitro in long-term cultures. The in vivo results showed that during the luteal phase of women with OHSS, there is no increase in 6-keto PGF1 alpha production compared with the levels obtained from the luteal phase of normal ovulatory women. The GLC (representing early corpus luteum function) secreted significant amounts of 6-keto PGF1 alpha, but only in the first 48 hours of culture. Human chorionic gonadotropin (hCG) had no additional augmentative effect upon the production of 6-keto PGF1 alpha throughout the culture period. It is concluded that 6-keto PGF1 alpha is not produced in significant amounts during the luteal phase, and therefore PG12 probably does not play a major role in the etiology of OHSS.


Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults.
In a double-blind, phase 3 trial, 663 HIV-infected, virologically suppressed adults were randomized to switch to tenofovir alafenamide (TAF; n = 333) vs. remain on tenofovir disoproxil fumarate (TDF; n = 330), each coformulated with emtricitabine (FTC), while continuing their third agent (boosted protease inhibitor or unboosted third agent). At week 96, 88.6% on FTC/TAF and 89.1% on FTC/TDF had HIV-1 RNA <50 copies per milliliter [adjusted difference -0.5% (95% confidence interval: -5.3 to 4.4%)]. Proteinuria, albuminuria, proximal renal tubular function, and bone mineral density improved after switching to TAF- from TDF-containing regimens. These longer-term data support FTC/TAF as a safe, well-tolerated, and durable nucleotide reverse transcriptase inhibitor backbone.


Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC.
The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes. GFC-induced autophagy of HT-29 cells was confirmed by observing the formation of acidic vesicular organelles, LC3 puncta, and double-membrane autophagic vesicles using flow cytometry, confocal microscopy, and transmission electron microscopy, respectively. Inhibition of AKT/mTOR/P70S6K signaling as well as formation of Atg5-Atg12 and PI3K/Beclin-1 complexes were observed using Western blot. Administration of autophagy inhibitor (3-methyladenine and shRNA Atg5) and apoptosis inhibitor Z-VAD showed that the GFC-induced autophagy was cytotoxic form and GFC-induced apoptosis enhanced GFC-induced autophagy. Our data suggest the involvement of autophagy and apoptosis in GFC-induced anticancer mechanisms of human colorectal cancer.


Interaction of ester functional groups with aluminum oxide surfaces studied using infrared reflection absorption spectroscopy.
The bonding of two types of ester group-containing molecules with a set of different oxide layers on aluminum has been investigated using infrared reflection absorption spectroscopy. The different oxide layers were made by giving typical surface treatments to the aluminum substrate. The purpose of the investigation was to find out what type of ester-oxide bond is formed and whether this is influenced by changes in the composition and chemistry of the oxide. The extent by which these bonded ester molecules resisted disbondment in water or substitution by molecules capable of chemisorption was also investigated. The ester groups were found to show hydrogen bonding with hydroxyls on the oxide surfaces through their carbonyl oxygens. For all oxides, the ester groups showed the same nu(C = O) carbonyl stretching vibration after adsorption, indicating very similar bonding occurs. However, the oxides showed differences in the amount of molecules bonded to the oxide surface, and a clear relation was observed with the hydroxyl concentration present on the oxide surface, which was determined from XPS measurements. The two compounds showed differences in the free to bonded nu(C = O) infrared peak shift, indicating differences in bonding strength with the oxide surface between the two types of molecules. The bonding of the ester groups with the oxide surfaces was found to be not stable in the presence of water and also not in the presence of a compound capable of chemisorption with the aluminum oxide surface.


[Constructed wetland and its application for industrial wastewater treatment].
This paper presents a review of the mechanisms and advantages of the constructed wetland (CW). The wetland as land-intensive biological treatment systems has complicated purificative mechanisms, including physio-chemistry such as substrate adsorption, substrate filtration, plant adsorption, pollutant sediment ion exchange and biochemistry such as plant sorption, microbiology oxidation, microbiology ammunition. Besides the aesthetic aspect of macrophytes to provide wildlife habitats, the advantages of CW are relatively low cost, simple operation with stable effluent quality and good resistance to shock loading. In recent years, these systems have been used in the purification of domestic sewage. Nowadays attention has focused particularly on the use of constructed wetlands for the treatment of industrial effluents. According to the study and present state of constructed wetland for industrial wastewater treatment, feasibility of CW for special industrial wastewater treatment and investigations in the future were discussed.


Estimation of Femoral Neck Anteversion in Adults: A Comparison Between Clinical Method, Radiography, and Computed Tomography at a Tertiary-care Center in Eastern India.
Introduction Femoral anteversion is the anterior inclination of the femoral neck and head in relation to the shaft of the femur. Femoral anteversion provides torsional stability of the hip - an important clinical factor for conditions such as trauma, arthroplasty, developmental dysplasia of the hip, and Legg-Calve Perthes disease. Precise measurement is important to avoid instability in pathological conditions of the hip. Computed tomography (CT) measures the angle more accurately as compared to plain radiography and is considered the gold standard procedure for measurement. Patients are exposed to significantly more ionizing radiation in CT, especially the pediatric population, which is more susceptible. Material and methods A prospective study of 25 individuals was undertaken wherein the femoral anteversion angle was comparatively measured by clinical, radiographic, and CT methods. Results The radiological evaluation depicted mean values that were far from those of the CT evaluation as compared to the clinical evaluation. Conclusion The clinical method (trochanter prominence angle test) can be used to measure femoral anteversion to avoid exposure to ionizing radiation and cases where CT is unavailable.


Quality & safety aspects of nuclear medicine practice: Definitions and review of the current literature.
Current literature records a glaring discrepancy between the rapid developments and progress of medicine and the simultaneous deterioration of the quality and safety of the provided health care services. Bibliographic data as far as perceptions of quality and safety in nuclear medicine departments are concerned, are limited and frequently ambiguous. Most nuclear medicine departments provide the same types of services, but not the same quality of service, while patients' perceptions are not always matched by the perceptions of health care providers. The multidimensional nature of quality and safety, deriving from the different criteria and standards by which different groups of the population attempt to interpret and evaluate them, justifies these discrepancies, over most of quality's and safety's dimensions studied. Nuclear medicine's unique characteristic of using radiopharmaceuticals, exposing to ionizing radiation affects dramatically these perceptions, irrespective of whether quality and safety assurance measures already cover radiation protection, instrumentation maintenance, radiopharmaceutical handling, and the management of all the other aspects of patient care. On the other end of the spectrum, patient-centred practice, communication and proper information play as a well decisive role in ensuring patients' satisfaction.


Transgenic Drosophila carrying mammalian cytochrome P-4501A1: an application to toxicology testing.
Transgenic Drosophila which carry a canine cytochrome P-450 were established and evaluated for its value on toxicology testing. Dah1, a cDNA clone for the canine hepatic P-4501A1, was ligated between the promoter of Drosophila heat-shock protein gene and the terminator of actin 5C gene, and then microinjected into Drosophila embryos with a transposon P element. The injected DNA was stably integrated into chromosomal DNA in germ line cells. After heat-shock treatments, transgenic larvae produced mRNA and a detectable amount of protein that cross-reacted with antibodies against rat P-4501A1. The ability of transgenic flies to activate procarcinogens was monitored in the DNA repair test with the endpoint being preadult mortality of repair-defective mei-9a mei-41D5/Y males. Heat-shock treatments of larvae showed that the repair-defective males carrying the P-4501A1 transgene were killed by lower concentrations of 7,12-dimethylbenz[a]anthracene than their non-transgenic or non heat-shocked counterparts. Coadministration of alpha-naphthoflavone, one of the inhibitors of P-4501A subfamily, cancelled the enhanced mortality of transgenic males, supporting that 7,12-dimethylbenz[a]anthracene was metabolized to its genotoxic form by the expressed P-4501A1 enzyme. This study indicates a potential utility of transgenic Drosophila for screening mammalian promutagens and procarcinogens.


Fibrinopeptides. IV. Synthesis of human fibrinopeptide A.
Human fibrinopeptide A, a hexadecapeptide, released by the action of thrombin on fibrinogen during clotting of blood, has been synthesized by conventional methods. The synthetic peptide as well as some of the intermediates in the synthesis have been examined for anticoagulant activity. Though all of them were found to be active, the terminal carboxyl protected peptides are more potent inhibitors of clotting than the carboxyl free peptides.


Multiplicity of acquired cross-resistance in paclitaxel-resistant cancer cells is associated with feedback control of TUBB3 via FOXO3a-mediated ABCB1 regulation.
Acquired drug resistance is a primary obstacle for effective cancer therapy. The correlation of point mutations in class III β-tubulin (TUBB3) and the prominent overexpression of ATP-binding cassette P-glycoprotein (ABCB1), a multidrug resistance gene, have been protruding mechanisms of resistance to microtubule disruptors such as paclitaxel (PTX) for many cancers. However, the precise underlying mechanism of the rapid onset of cross-resistance to an array of structurally and functionally unrelated drugs in PTX-resistant cancers has been poorly understood. We determined that our established PTX-resistant cancer cells display ABCB1/ABCC1-associated cross-resistance to chemically different drugs such as 5-fluorouracil, docetaxel, and cisplatin. We found that feedback activation of TUBB3 can be triggered through the FOXO3a-dependent regulation of ABCB1, which resulted in the accentuation of induced PTX resistance and encouraged multiplicity in acquired cross-resistance. FOXO3a-directed regulation of P-glycoprotein (P-gp) function suggests that control of ABCB1 involves methylation-dependent activation. Consistently, transcriptional overexpression or downregulation of FOXO3a directs inhibitor-controlled protease-degradation of TUBB3. The functional PI3K/Akt signaling is tightly responsive to FOXO3a activation alongside doxorubicin treatment, which directs FOXO3a arginine hypermethylation. In addition, we found that secretome factors from PTX-resistant cancer cells with acquired cross-resistance support a P-gp-dependent association in multidrug resistance (MDR) development, which assisted the FOXO3a-mediated control of TUBB3 feedback. The direct silencing of TUBB3 reverses induced multiple cross-resistance, reduces drug-resistant tumor mass, and suppresses the impaired microtubule stability status of PTX-resistant cells with transient cross-resistance. These findings highlight the control of the TUBB3 response to ABCB1 genetic suppressors as a mechanism to reverse the profuse development of multidrug resistance in cancer.


Single molecule quantitation and sequencing of rare translocations using microfluidic nested digital PCR.
Cancers are heterogeneous and genetically unstable. New methods are needed that provide the sensitivity and specificity to query single cells at the genetic loci that drive cancer progression, thereby enabling researchers to study the progression of individual tumors. Here, we report the development and application of a bead-based hemi-nested microfluidic droplet digital PCR (dPCR) technology to achieve 'quantitative' measurement and single-molecule sequencing of somatically acquired carcinogenic translocations at extremely low levels (<10(-6)) in healthy subjects. We use this technique in our healthy study population to determine the overall concentration of the t(14;18) translocation, which is strongly associated with follicular lymphoma. The nested dPCR approach improves the detection limit to 1×10(-7) or lower while maintaining the analysis efficiency and specificity. Further, the bead-based dPCR enabled us to isolate and quantify the relative amounts of the various clonal forms of t(14;18) translocation in these subjects, and the single-molecule sensitivity and resolution of dPCR led to the discovery of new clonal forms of t(14;18) that were otherwise masked by the conventional quantitative PCR measurements. In this manner, we created a quantitative map for this carcinogenic mutation in this healthy population and identified the positions on chromosomes 14 and 18 where the vast majority of these t(14;18) events occur.


Visual Diagnosis: A 7-Month-Old Girl With Cyanotic Spells.
Infants can develop acquired methemoglobinemia due to intake of well water high in nitrate concentrations. Although methemoglobinemia usually presents with more severe symptoms, this diagnosis should be considered in an infant with intermittent cyanosis in the absence of underlying heart or lung disease. Well water should be avoided in infancy unless properly tested.


Regulation of isotype production by IL-4 and IL-5. Effects of lymphokines on Ig production depend on the state of activation of the responding B cells.
The effects of IL-4 and IL-5 on the production of Ig of different isotypes was investigated. We compared B cells from spleen and from Peyer's patches either stimulated with LPS or without added polyclonal stimulation. We also compared high density (small) and low density (large) B cells. The effect of lymphokines depended on the size and source of the B cells as well as on whether LPS was added. As expected, small B cells from either lymphoid compartment responded to LPS alone and IL-4 suppressed IgM and IgG3 production and enhanced IgG1. In contrast, when large B cells were examined, the suppressive effects of IL-4 were much less apparent but the enhancement of IgG1 was still marked. IL-5 alone had only minimal effects in LPS-stimulated cultures but the combination of IL-4 plus IL-5 appeared to overcome much of the IL-4-mediated suppression of IgM, and IgA production was enhanced. In the absence of LPS, a quite different profile is seen. First, small B cells make little if any response. Second, there is dramatic synergy between IL-4 and IL-5 in the response of large B cells, which is independent of isotype. Third, IL-4 does not suppress any isotype in the absence of LPS. Fourth, IL-4 plus IL-5 stimulate large Peyer's patch B cells to produce 10 times more IgA but three times less IgM than large spleen B cells. Fifth, Th2 cells directly stimulate both large and small B cells.


Postdischarge Major Adverse Cardiovascular Events of ICU Survivors Who Received Acute Renal Replacement Therapy.
Long-term risk of a major adverse cardiovascular events in ICU survivors who underwent acute renal replacement therapy requires further investigation. Nationwide population-based study using the claims database of Korea. Index admission cases of ICU survivors in government-designated tertiary hospitals PATIENTS:: The study group consisted of ICU survivors who underwent acute renal replacement therapy, and the control group consisted of those without acute renal replacement therapy. Patients were excluded if they 1) were under age 20, 2) expired within 30 days after discharge, 3) received ICU care for less than 24 hours, 4) had a previous ICU admission, 5) had a history of major adverse cardiovascular event, or 6) had a major adverse cardiovascular event-related cardio/cerebrovascular diseases. The outcomes of the patients who received continuous renal replacement therapy were compared with those of patients who received only intermittent renal replacement therapy. None. Information regarding patient characteristics and treatment modalities was collected and adjusted. The main outcome was major adverse cardiovascular event, including acute myocardial infarction, revascularization, and acute ischemic stroke. Patient mortality and progression to end-stage renal disease were also evaluated. We included 12,380 acute renal replacement therapy patients and 382,018 patients in the control group. Among the study group, 6,891 patients were included in the continuous renal replacement therapy group, and 5,034 in the intermittent renal replacement therapy group. The risks of major adverse cardiovascular event (adjusted hazard ratio, 1.463 [1.323-1.619]; p < 0.001), all-cause mortality (adjusted hazard ratio, 1.323 [1.256-1.393]; p < 0.001), and end-stage renal disease (adjusted hazard ratio, 18.110 [15.779-20.786]; p < 0.001) were higher in the acute renal replacement therapy patients than the control group. When we compared the continuous renal replacement therapy patients with the intermittent renal replacement therapy patients, the risk of major adverse cardiovascular event was comparable (adjusted hazard ratio, 1.049 [0.888-1.239]; p = 0.575). Clinicians should note the increased risk of a long-term major adverse cardiovascular event in acute renal replacement therapy patients and consider appropriate risk factor management. Significant difference in the risk of postdischarge major adverse cardiovascular event was not identified between continuous renal replacement therapy and intermittent renal replacement therapy.


Characterization of growth and development of sorghum genotypes with differential susceptibility to Striga hermonthica.
Two sorghum varieties, Shanqui Red (SQR) and SRN39, have distinct levels of susceptibility to the parasitic weed Striga hermonthica, which have been attributed to different strigolactone composition within their root exudates. Root exudates of the Striga-susceptible variety Shanqui Red (SQR) contain primarily 5-deoxystrigol, which has a high efficiency for inducing Striga germination. SRN39 roots primarily exude orobanchol, leading to reduced Striga germination and making this variety resistant to Striga. The structural diversity in exuded strigolactones is determined by a polymorphism in the LOW GERMINATION STIMULANT 1 (LGS1) locus. Yet, the genetic diversity between SQR and SRN39 is broad and has not been addressed in terms of growth and development. Here, we demonstrate additional differences between SQR and SRN39 by phenotypic and molecular characterization. A suite of genes related to metabolism was differentially expressed between SQR and SRN39. Increased levels of gibberellin precursors in SRN39 were accompanied by slower growth rate and developmental delay and we observed an overall increased SRN39 biomass. The slow-down in growth and differences in transcriptome profiles of SRN39 were strongly associated with plant age. Additionally, enhanced lateral root growth was observed in SRN39 and three additional genotypes exuding primarily orobanchol. In summary, we demonstrate that the differences between SQR and SRN39 reach further than the changes in strigolactone profile in the root exudate and translate into alterations in growth and development.


Finding functionality: Rasch analysis of the Functionality Appreciation Scale in community-dwelling adults in the US.
The Functionality Appreciation Scale (FAS) measures an individual's appreciation for the functions their body can perform, regardless of the individual's physical limitations. Prior studies reported on internal consistency, test-retest reliability, convergent validity, and exploratory or confirmatory factor analyses, but Rasch analysis has not yet been performed to evaluate the structural validity of the FAS. We recruited community-dwelling adults at the Minnesota State Fair and through contact lists of participants identifying interest in research done in the Brain Body Mind Lab (University of Minnesota). Community-dwelling adults with spinal cord injury (SCI) completed the FAS over Zoom. We analyzed the FAS using Rasch Measurement Theory, which produced the following outputs: item, and person fit, targeting, unidimensionality, person separation reliability (PSR), local item dependence (LID), principal component analysis of residuals (PCAR), and differential item functioning (DIF). We recruited 567 participants (average age 52.15 ± 17.5 years, 63.84% women), among which 14 adults with SCI. After rescoring 3 items and deleting 1 item, the FAS had good person and item fit (except item 4). The PCAR and subsequent paired t-tests (3.53%) confirmed the unidimensionality of the scale. There was no DIF and only one item pair had LID (item 5-6). PSR was 0.75, reflecting a capacity to differentiate groups of people with high or low functionality appreciation levels. However, there was a significant ceiling effect (28.04%) and the person mean location was 3.06 ± 2.07 logits, indicating the FAS is too easy for community-dwelling adults in the US. The 6-item Rasch-based FAS demonstrated unidimensionality, good item fit (except item 4) and person fit, but the FAS will require more difficult items to be added to improve the targeting of the scale, and better reliability.


Accidental damage to teeth adjacent to crown-prepared abutment teeth.
Three hundred and seventy casts with 652 registrable proximal surfaces adjacent to crown preparations were examined for iatrogenic damage to hard tissue surfaces. The incidence of damage was high and recommendations for prevention and treatment of such damage are made.


The role of fluorodeoxyglucose-PET/computed tomography as a predictor of breast cancer characteristics and prognosis.
Fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) affects the management of patients with breast cancer. Our study aimed to determine the predictive ability of characteristics such as lymph node involvement or subtype and the prognostic value of pretreatment FDG-PET/CT in breast cancer. A total of 270 patients who were confirmed with breast cancer histopathologically and underwent pretreatment FDG-PET/CT were enrolled in the study. Nuclear medicine specialists obtained the readings and measured the maximum standardized uptake value (SUVmax) of the images. Tumor and lymph node SUVmax were evaluated according to lymph node metastasis and subtype status. Survival outcomes were analyzed by the Kaplan-Meier method. The lymph node SUVmax and the lymph node/tumor SUVmax ratio were significantly higher in the subgroup of patients with lymph node metastasis than in those without lymph node metastasis. High cutoff lymph node SUVmax value and lymph node/tumor SUVmax ratio were confirmed as significant predictive factors in multivariate analysis. In a comparison of the tumor SUVmax values, the more biological aggressive subtype showed higher tumor SUVmax values. In survival analysis, tumor SUVmax and lymph node SUVmax were significant predisposing factors for disease-free survival in breast cancer. In subgroup analysis, tumor SUVmax was a more significant prognostic factor in patients who had breast cancer with tumor sizes of ≤2 cm. The lymph node SUVmax was more a significant prognostic factor in patients who had breast cancer with lymph node metastasis. In this study, we showed that the SUVmax of FDG-PET/CT was a useful predictor of lymph node metastasis and breast cancer prognosis.


Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL.
REVEAL was a 52-week phase III trial of adalimumab therapy for moderate to severe chronic plaque psoriasis. Patients from REVEAL could enter an open-label extension trial to receive adalimumab for approximately 3 years of total therapy. We sought to determine long-term efficacy and safety of continuous adalimumab therapy for patients from REVEAL. Efficacy and safety over greater than 3 years of treatment were analyzed for 4 groups of patients from REVEAL. Patients who received adalimumab continuously from baseline were grouped by their responses in REVEAL: (1) greater than or equal to 75% improvement in Psoriasis Area and Severity Index (PASI) score (PASI 75) at weeks 16 and 33 (sustained responders); (2) less than PASI 75 at week 16; and (3) greater than or equal to PASI 75 at week 16 with 50% to less than 75% improvement in PASI score at week 33. Results were also analyzed for patients who began adalimumab after 16 weeks of placebo therapy. For patients with sustained PASI 75 responses during REVEAL, efficacy was generally well maintained over 3 years, with 75%/90%/100% improvement in PASI score response rates (last observation carried forward) of 83%/59%/33% after 100 weeks and 76%/50%/31% after 160 weeks of continuous therapy. Some patients with less than PASI 75 responses in REVEAL also achieved long-term PASI 75 responses. Efficacy in the placebo/adalimumab group was consistent with the ensemble of results from the other 3 groups. Adverse event rates were consistent with those during REVEAL. The REVEAL study design prevented analyzing all patients from the adalimumab arm as one long-term cohort. Adalimumab efficacy was well maintained over more than 3 years of continuous therapy for patients with sustained initial PASI 75 responses. Maintenance was best at the PASI 100 level.


Cardioprotection Effects of Sevoflurane by Regulating the Pathway of Neuroactive Ligand-Receptor Interaction in Patients Undergoing Coronary Artery Bypass Graft Surgery.
This study was designed to identify attractor modules and further reveal the potential biological processes involving in sevoflurane-induced anesthesia in patients treated with coronary artery bypass graft (CABG) surgery. Microarray profile data (ID: E-GEOD-4386) on atrial samples obtained from patients receiving anesthetic gas sevoflurane prior to and following CABG procedure were downloaded from EMBL-EBI database for further analysis. Protein-protein interaction (PPI) networks of baseline and sevoflurane groups were inferred and reweighted according to Spearman correlation coefficient (SCC), followed by systematic modules inference using clique-merging approach. Subsequently, attract method was utilized to explore attractor modules. Finally, pathway enrichment analyses for genes in the attractor modules were implemented to illuminate the biological processes in sevoflurane group. Using clique-merging approach, 27 and 36 modules were obtained from the PPI networks of baseline and sevoflurane-treated samples, respectively. By comparing with the baseline condition, 5 module pairs with the same gene composition were identified. Subsequently, 1 out of 5 modules was identified as an attractor based on attract method. Additionally, pathway analysis indicated that genes in the attractor module were associated with neuroactive ligand-receptor interaction. Accordingly, sevoflurane might exert important functions in cardioprotection in patients following CABG, partially through regulating the pathway of neuroactive ligand-receptor interaction.


Reversal of drug resistance in a human colon cancer xenograft expressing MDR1 complementary DNA by in vivo administration of MRK-16 monoclonal antibody.
One strategy to overcome multidrug resistance in neoplasia is to inhibit the gp170 glycoprotein (relative molecular mass, 170,000) that functions as a plasma membrane, energy-dependent, drug-efflux pump. The human colon cancer cell line HT-29, which grows as an ascitic tumor in athymic NCr-nu/nu nude mice, was made multidrug resistant by infection with an MDR1 (also known as PGY1) retrovirus. Referred to as HT-29mdr1, it was used to study reversal of drug resistance in vivo by the anti-P-glycoprotein monoclonal antibody MRK-16. Flow cytometry and radioimmunoassay demonstrated a marked increase in MRK-16 reactivity on HT-29mdr1 cells as compared with its reactivity on the parental, uninfected cell line (HT-29par). The 50% inhibitory concentrations (IC50) of vincristine on HT-29par and HT-29mdr1 cells were 2.5 and 15 ng/mL, respectively. The MRK-16 monoclonal antibody did not affect the vincristine sensitivity of the HT-29par cells. Pretreatment of HT-29mdr1 cells with 10 micrograms/mL MRK-16 in tissue culture partially restored the vincristine sensitivity (IC50 = 7 ng/mL). This modulation of vincristine sensitivity by MRK-16 was then tested in vivo. The median survival times of mice given intraperitoneal transplants of 5 x 10(6) HT-29par or HT-29mdr1 were 37 and 39 days, respectively. Treatment of mice with 1 mg/kg vincristine weekly for 3 weeks, beginning 10 days after tumor injection, resulted in a significant increase in the median survival time of the HT-29par tumor-bearing mice (68 days, P less than .0001), but it had no effect on the HT-29mdr1 tumor-bearing mice. However, treatment of mice bearing the HT-29mdr1 tumor with MRK-16 before vincristine therapy reversed the resistance to the drug (median survival time = 64 days, P less than .0001). The MRK-16 monoclonal antibody alone had no effect on the median survival time of mice given an injection of either HT-29par or HT-29mdr1 cells. These results suggest that strategies employing monoclonal antibody against gp170 may be clinically useful to reverse multidrug resistance.


Effect of phenol on haematological components of Indian major carps Catla catla, Labeo rohita and Cirrhinus mrigala.
The effect of phenol on haematological components of Indian major carps, Catla catla, Labeo rohita and Cirrhinus mrigala were observed. After exposure to sublethal concentrations of 5.17 mg l(-1), 6.06 mg l(-1) and 6.99 mg l(-1), the number of red blood cells, haemoglobin content and packed cell volume all decreased but the glucose level increased. The order of decrease in the haematological components of the three fish is in the order of Catla catla > Labeo rohita > Cirrhinus mrigala.


Localization of left ventricular outflow obstruction by cross-sectional echocardiography.
Cross-sectional echocardiographic studies were performed using a high resolution real time mechanical sector scanner in 70 patients with left ventricular outflow obstruction. Seven separate obstructive patterns were recorded in these patients. An area of aortic narrowing just distal to the aortic valve at the superior border of the left atrium was noted with supravalvular aortic stenosis. With congenital valvular aortic stenosis there was an increase in echo production by the thickened aortic leaflets. During systole these prominent leaflet echoes curved inward toward the center of the aortic root reflecting the systolic doming of the valve. With calcific aortic stenosis, the calcification produced an area of dense linear echoes attached in varying degrees to either the anterior or posterior border of the aortic root. At the subvalvular level three obstructive patterns were recorded; with a discrete subvalvular obstructive membrane two linear echoes apparently produced by the inner margins of the obstructing membrane were recorded in the outflow tract. With more extensive fibromuscular narrowing of the subvalvular area, there was inward bowing of the echoes from both the anterior and posterior walls of the outflow tract. In one case this was a dense shelf-like mass of echoes extending downward from the basal portion of the interventricular septum toward the mid-portion of the anterior mitral leaflet with corresponding systolic anterior motion of the mitral leaflet. In patients with idiopathic hypertrophic subaortic stenosis there was systolic anterior motion of the anterior mitral leaflet beginning just distal to the point of coaptation of the mitral leaflets and extending distally toward the papillary muscles. This report suggests that the enlarged field of vision and spatial orientation provided by the cross-sectional echocardiographic technic should improve our ability to record and characterize areas of obstruction to left ventricular outflow.


Biomarkers in systemic sclerosis: mechanistic insights into pathogenesis and treatment.
Systemic sclerosis (SSc) is heterogenous on molecular, cellular, tissue, and clinical levels. Although many biomarkers have been described in clinical studies, few have been rigorously mapped to specific molecular pathways, tissue pathologies, and clinical manifestations. A focused assessment of peripheral blood levels of C-C Motif Chemokine Ligand-18 (CCL18) and periostin illustrates how biomarkers can link molecular mediators to clinical outcomes. CCL18 is produced by pulmonary macrophages in response to type 2 cytokines and IL6. Elevated serum CCL18 is associated with interstitial lung disease (ILD) in SSc patients and is prognostic for ILD progression. It is pharmacologically modulated by IL6 inhibition, and associated with stabilization of lung function decline but not with improvements in skin fibrosis. Periostin is produced by dermal fibroblasts in SSc in response to type 2 cytokines and transforming growth factor-beta. Elevated serum periostin is associated with cutaneous disease in SSc patients but not ILD. Other cell- and tissue-specific biomarkers detectable in peripheral blood and informative with respect to SSc pathogenesis include KL-6 and SP-D in lung epithelium, osteopontin in lung macrophages, and cartilage oligomeric matrix protein in dermal fibroblasts. Blood biomarkers related to specific molecular mediators, cell types, and tissues of origin can help to link therapeutic targets to treatable traits in SSc.


GO/PEDOT:PSS nanocomposites: effect of different dispersing agents on rheological, thermal, wettability and electrochemical properties.
In this work glucose (G), α-cyclodextrin (α-CD) and sodium salt of carboxymethyl cellulose (CMCNa) are used as dispersing agents for graphene oxide (GO), exploring the influence of both saccharide units and geometric/steric hindrance on the rheological, thermal, wettability and electrochemical properties of a GO/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) nanocomposite. By acting on the saccharide-based additives, we can modulate the rheological, thermal, and wettability properties of the GO/PEDOT:PSS nanocomposite. Firstly, the influence of all the additives on the rheological behaviour of GO and PEDOT:PSS was investigated separately in order to understand the effect of the dispersing agent on both the components of the ternary nanocomposite, individually. Subsequently, steady shear and dynamic frequency tests were conducted on all the nanocomposite solutions, characterized by thermal, wettability and morphological analysis. Finally, the electrochemical properties of the GO/PEDOT composites with different dispersing agents for supercapacitors were investigated using cyclic voltammetry (CV). The CV results revealed that GO/PEDOT with glucose exhibited the highest specific capacitance among the systems investigated.


Epac-mediated activation of phospholipase C(epsilon) plays a critical role in beta-adrenergic receptor-dependent enhancement of Ca2+ mobilization in cardiac myocytes.
Recently we demonstrated that PLC(epsilon) plays an important role in beta-adrenergic receptor (betaAR) stimulation of Ca(2+)-induced Ca(2+) release (CICR) in cardiac myocytes. Here we have reported for the first time that a pathway downstream of betaAR involving the cAMP-dependent Rap GTP exchange factor, Epac, and PLC(epsilon) regulates CICR in cardiac myocytes. To demonstrate a role for Epac in the stimulation of CICR, cardiac myocytes were treated with an Epac-selective cAMP analog, 8-4-(chlorophenylthio)-2'-O-methyladenosine-3',5'-monophosphate (cpTOME). cpTOME treatment increased the amplitude of electrically evoked Ca(2+) transients, implicating Epac for the first time in cardiac CICR. This response is abolished in PLC(epsilon)(-/-) cardiac myocytes but rescued by transduction with PLC(epsilon), indicating that Epac is upstream of PLC(epsilon). Furthermore, transduction of PLC(epsilon)(+/+) cardiac myocytes with a Rap inhibitor, RapGAP1, significantly inhibited isoproterenol-dependent CICR. Using a combination of cpTOME and PKA-selective activators and inhibitors, we have shown that betaAR-dependent increases in CICR consist of two independent components mediated by PKA and the novel Epac/(epsilon) pathway. We also show that Epac/PLC(epsilon)-dependent effects on CICR are independent of sarcoplasmic reticulum loading and Ca(2+) clearance mechanisms. These data define a novel endogenous PKA-independent betaAR-signaling pathway through cAMP-dependent Epac activation, Rap, and PLC(epsilon) that enhances intracellular Ca(2+) release in cardiac myocytes.


Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years.
The membrane lipid composition of human frontal and temporal cortices and white matter has been studied in 118 subjects, age 20-100 years. The brain specimens were selected from subjects who lived a normal social life and died suddenly and unexpectedly with no history of neurologic or psychiatric disease. Macroscopic and microscopic examinations ruled out any signs of organic brain disorder. The sudden death eliminated all risk of changes over a long agonal stage. The data for total solids and major lipids are summarized in graphic form. Total solids, phospholipids, and cholesterol diminished linearly from 20 years of age in frontal and temporal cortices, whereas total solids phospholipids, cholesterol, cerebroside, and sulfatide showed a curvilinear diminution in frontal and temporal white matter. Gangliosides differed from the other lipids, showing an almost constant concentration between 20 and 70 years of age with a slight peak around 50 years of age. The ganglioside pattern showed continuous change with aging, with decreasing proportions of GM1 and GD1a and increasing proportions of GD1b, GM3, and GD3. Equations are given that can be used to calculate the lipid composition of normal human frontal and temporal cortices and white matter at any age between 20 and 100 years of age. These data can be used where data by direct analysis are not available for comparison with values for various pathological states.


Spontaneous Rupture of Pyometra in a Nonpregnant Young Woman.
A 40-year-old woman presented with severe vaginal bleeding. Initial workup with an abdominal sonography revealed endometrium for about 3 mm and free fluid in the abdomen. Hemodynamic instability with abdominal pain and free fluid in the abdomen prompted blood transfusion and laparotomy. There were about 1000 cc blood and clots in the abdomen at laparotomy. There was a longitudinal rupture from fundus up to cervix at the left side of the uterus. Tearing was in full thickness from serosa to endometrium. Scar of previous cesarean was transvers and not associated with this tearing. There was not any myomectomy scar.


Exploring the Multicomponent Synergy Mechanism of Yinzhihuang Granule in Inhibiting Inflammation-Cancer Transformation of Hepar Based on Integrated Bioinformatics and Network Pharmacology.
The Chinese patent drug Yinzhihuang granule (YZHG) is used to treat hepatitis B. This research is aimed at exploring the multicomponent synergistic mechanism of YZHG in the treatment of inflammation-cancer transformation of hepar and at providing new evidence and insights for its clinical application. To retrieve the components and targets of Yinzhihuang granules. The differentially expressed genes (DEGs) of hepar inflammation-cancer transformation were obtained from TTD, PharmGKB, and GEO databases. Construct the compound-prediction target network and the key module network using Cytoscape 3.7.1. The results show that hepatitis B and hepatitis C shared a common target, MMP2. CDK1 and TOP2A may play an important role in the treatment with YZHG in hepatitis B inflammatory cancer transformation. KEGG pathway enrichment showed that key genes of modules 1, 2, and 4 were mainly enriched in the progesterone-mediated oocyte maturation signaling pathway and oocyte meiosis signaling pathway. The multicomponent, multitarget, and multichannel pharmacological benefits of YZHG in the therapy of inflammation-cancer transition of hepar are directly demonstrated by network pharmacology, providing a scientific basis for its mechanism.


Echinocandins: production and applications.
The first echinocandin-type antimycotic (echinocandin B) was discovered in the 1970s. It was followed by the isolation of more than 20 natural echinocandins. These cyclic lipo-hexapeptides are biosynthesized on non-ribosomal peptide synthase complexes by different ascomycota fungi. They have a unique mechanism of action; as non-competitive inhibitors of β-1,3-glucan synthase complex they target the fungal cell wall. Results of the structure-activity relationship experiments let us develop semisynthetic derivatives with improved properties. Three cyclic lipohiexapeptides (caspofungin, micafungin and anidulafungin) are currently approved for use in clinics. As they show good fungicidal (Candida spp.) or fungistatic (Aspergillus spp.) activity against the most important human pathogenic fungi including azole-resistant strains, they are an important addition to the antifungal armamentarium. Some evidence of acquired resistance against echinocandins has been detected among Candida glabrata strains in recent years, which enhanced the importance of data collected on the mechanism of acquired resistance developing against the echinocandins. In this review, we show the structural diversity of natural echinocandins, and we summarize the emerging data on their mode of action, biosynthesis and industrial production. Their clinical significance as well as the mechanism of natural and acquired resistance is also discussed.


A Prospective, Experimental Study to Assess the Effectiveness of Home Care Nursing on the Healing of Peristomal Skin Complications and Quality of Life.
Home care services are effective in many patient groups. The authors examined the effect of specialized ostomy care in the home on peristomal skin complications and patient quality of life (QOL). A prospective, experimental study was conducted among 35 people >18 years old with a colostomy or ileostomy and peristomal skin complications who were listed in 2 ostomy supplier databases. Participants were alternatively allocated to 6 home care visits (intervention [IG], n = 18) or 2 outpatient/clinic care [CG] visits (control, n = 17). Demographic and patient variables were assessed at the initial visit in both groups. The Ostomy Skin Tool (OST) and the Stoma-Quality of Life instrument were used to assess study characteristics; data were statistically analyzed. The Discoloration, Erosion, Tissue Overgrowth scores of the OST of the 2 groups were similar in the first assessment (IG = 6.22 ± 1.47; CG= 6.11 ± 1.96; P = .776), but a statistically significant difference was noted between groups at the end of study (IG = 0.44 ± 0.85, CG = 4.76 ± 2.30; P = .00). At the first assessment, QOL scores of the IG and CG groups were 72.63 ± 11.48 and 66.73 ± 17.52, respectively (P = .197). At the final assessment, QOL scores were 78.12 ± 9.66 and 71.83 ± 18.37 for IG and CG, respectively (P = .390). Home nursing care was found to be effective in treating peristomal skin complications. The QOL scores achieved at the final assessment were significantly improved compared with the initial assessment. The results demonstrated the importance of follow-up after stoma surgery.


Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes.
The high mutation rate of HIV is linked to the generation of viruses expressing proteins with altered function whose impact on disease progression is unknown. We investigated how HIV-1 viruses lacking Env, Vpr, and Nef affect CD4(+) T cell survival. We found that in the absence of these proteins, HIV-1-infected CD4(+) primary T cells progress to the G(0) phase of the cell cycle and to cell death, indicating that viruses expressing inactive forms of these proteins can contribute to the CD4(+) T cell decline as the wild-type virus, suggesting that other HIV proteins are responsible for inducing apoptosis. Apoptosis in these cells is triggered by the alteration of the Egr1-PTEN-Akt (early growth response-1/phosphate and tensin homolog deleted on chromosome 10/Akt) and p53 pathways, which converge on the FOXO3a (Forkhead box transcription factor O class 3a) transcriptional activator. The FOXO3a target genes Fas ligand and TRAIL, involved in the extrinsic apoptotic pathway, and PUMA, Noxa, and Bim, which are part of the intrinsic apoptotic pathway, were also up-regulated, indicating that HIV infection leads to apoptosis by the engagement of multiple apoptotic pathways. RNAi-mediated knockdown of Egr1 and FOXO3a resulted in reduced apoptosis in HIV-infected HeLa and CD4(+) T cells, providing further evidence for their critical role in HIV-induced apoptosis and G(0) arrest. We tested the possibility that Tat is responsible for the T cell apoptosis observed with these mutant viruses. The induction of Egr1 and FOXO3a and its target genes was observed in Jurkat cells transduced by Tat alone. Tat-dependent activation of the Egr1-PTEN-FOXO3a pathway provides a mechanism for HIV-1-associated CD4(+) T cell death.


Calcium-dependent conformational change and thermal stability of the isolated PsbO protein detected by FTIR spectroscopy.
The structure and function of the photosystem II PsbO extrinsic protein is under intense research, being an essential part of the biomolecular engine that carries out water oxidation and oxygen production. This paper presents a structural analysis of the isolated PsbO protein by FTIR spectroscopy, reporting detailed secondary structure quantification and changes in the secondary structure content of the protein attributed to the effect of calcium (Ca(2+)). Measurements in H(2)O and D(2)O have allowed us to see the effect of calcium on the conformation of the protein. The results indicate that (i) the protein presents a major content of beta-structure (i.e., beta-sheet, beta-strands, beta-turns) as detected by the infrared bands at 1624-1625, 1678-1679, 1688-1689 cm(-1), which account for about 38% in water and 33% in heavy water, in the presence of calcium; and (ii) the amount of this beta-structure fraction increases 7-10% in the absence of calcium, with a concomitant decrease in loops and nonordered structure. The thermal denaturation profile of the protein in the presence of calcium showed low stability with T(m) approximately 56 degrees C. This profile also shows a second phase of denaturation above 60 degrees C and the appearance of aggregation signals above 70 degrees C. Our observations indicate that calcium is able to modify the conformation of the protein at least in solution and confirm that PsbO is mainly a beta-protein where beta-sheet is the major ordered secondary structure element of the protein core.


NIR-based Sensing System for Non-invasive Detection of Hemoglobin for Point-of-care Applications.
Hemoglobin is an essential biomolecule for the transportation of oxygen, therefore, its assessment is also important to be done frequently in numerous clinical practices. Traditional invasive techniques have concomitant shortcomings, such as time delay, the onset of infections, and discomfort, which necessitate a non-invasive hemoglobin estimation solution to get rid of these constraints in health informatics. Currently, various techniques are underway in the allied domain, and scanty products are also feasible in the market. However, due to the low satisfaction rate, invasive solutions are still assumed as the gold standard. Recently introduced technologies effectively evolved as optical spectroscopy and digital photographic concepts on different sensing spots, e.g., fingertip, palpebral conjunctiva, bulbar conjunctiva, and fingernail. Productive sensors develop more than eight wavelengths to compute hemoglobin concentration and four wavelengths to display only Hb-index (trending of hemoglobin) either in disposable adhesive or reusable cliptype sensor's configuration. This study aims at an optimistic optical spectroscopic technique to measure hemoglobin concentration and conditional usability of non-invasive blood parameters' diagnostics at point-ofcare. Two distinguishable light emitting sources (810 nm and 1300 nm) are utilized at isosbestic points with a single photodetector (800-1700 nm). With this purpose, reusable finger probe assembly is facilitated in transmittance mode based on the newly offered sliding mechanism to block ambient light. Investigation with proposed design presents correlation coefficients between reference hemoglobin and every individual feature, a multivariate linear regression model for highly correlated independent features. Moreover, principal component analytical model with multivariate linear regression offers mean bias of 0.036 and -0.316 g/dL, precision of 0.878 and 0.838 and limits of agreement from -1.685 to 1.758 g/dL and -1.790 to 1.474 g/dL for 18 and 21 principal components, respectively. The encouraging readouts emphasize favorable precision; therefore, it is proposed that the sensing system is amenable to assess hemoglobin in settings with limited resources and strengthening future routes for the point of care applications.


[The influence of cholesterol feeding on the anastomotic region of the induced atherosclerotic rabbit vessels--especially on the late occlusive process].
Late occlusive complication of implanted graft may occur 6 months to 5 years after operation. The most frequent cause of this condition is considered to be an intimal thickening at the anastomotic sites. The relationship between this intimal thickening and cholesterol feeding in rabbits was investigated. Twenty eight male New Zealand White Rabbits were assigned following 4 groups. Group 1: given 0.1% cholesterol containing rabbit pellets after denudation of endothelium Group 2: given standard laboratory rabbit pellets after denudation Group 3: given 0.1% cholesterol rabbit pellets without denudation Group 4: given standard rabbit pellets without denudation Anterior half of infrarenal abdominal aorta of all rabbits was incised and then continuous over and over suture was carried out. Three months later, rabbits were killed and specimens were obtained. In group 1, 3 specimens out of 7 were found significant intimal thickening near anastomosis, whereas, in group 2 specimens showed regular thickening which seemed to be affected by denudation of endothelium. In group 3, intimal thickening localized only near anastomosis was found. From these results, we concluded intimal thickening at the anastomotic sites can be considered as the initial stage of atherosclerosis and cholesterol would be one of the important factors which promote this thickening.


Virologic studies on cattle with naturally occurring and experimentally induced malignant catarrhal fever.
Malignant catarrhal fever is an important disease of cattle and certain wild ruminants. It occurs in sporadic and epizootic forms in Colorado cattle. Specimens from 15 cattle with naturally occurring malignant catarrhal fever and 5 cattle with induced disease were examined for cell-free and cell-associated viruses. Enteroviruses were isolated from leukocytes of 2 cattle with field cases of the disease. A herpesvirus with characteristics of the "Movar"-type, isolated from the spleen of another steer with a field case could be propagated optimally in bovine fetal spleen cells. A cell-associated virus, forming polykaryons, was isolated in adrenal and thyroid cells from 3 cattle with experimentally induced malignant catarrhal fever. It was cultured from leukocytes, ependymal tissue, spleen, lymph node, kidney and thyroid and adrenal glands of affected cattle and remained cell-associated in 48 subsequent passages. It was inactivated by freezing and thawing and by treatment with ultrasound; its polykaryon-forming activity was inhibited by 25 mug of 5 fluoro-2' deoxyuridine/ml. This viral agent replicated in bovine fetal adrenal, thyroid, and spleen cells, but not in primary kidney cells or in MDBK, HeLa, or L cells. A representative isolate was identified electronmicroscopically as an enveloped virus, 120 to 150 nm in diameter. Structural analysis indicated that it had properties of the bovine syncytial viruses. Attempts to induce MCF in cattle with 1 of the isolates failed. A parvovirus was isolated from the jejunal lymph node of calf 72-P-293, which had the experimentally induced disease and was also infected with the syncytial virus.


Unexpected intermediates and products in the C-F bond activation of tetrafluorobenzenes with a bis(triethylphosphine)nickel synthon: direct evidence of a rapid and reversible C-H bond activation by Ni(0).
The reaction of (PEt(3))(2)Ni(eta(2)-C(14)H(10)), a source of the reactive Ni(PEt(3))(2) moiety, with 1,2,4,5-F(4)C(6)H(2) yields a mixture of three C-F bond activation products that include the unexpected products (PEt(3))(2)NiF-2,3,5,6-F(4)C(6)H and (PEt(3))(2)NiF-2,3,5-F(3)C(6)H(2). Monitoring the reaction mixture via (19)F and (1)H NMR also reveals the presence of the C-H bond activation product, (PEt(3))(2)NiH-2,3,5,6-F(4)C(6)H which is produced in a rapid equilibrium reaction. This observation provides insight into the steps necessary to modify nickel complexes for selective C-F bond activation in a variety of polyfluorinated aromatic substrates, but also expands the potential of simple nickel compounds for C-H bond activation and functionalization reactions.


Dynamic Contact Angle at the Nanoscale: A Unified View.
Generation of a dynamic contact angle in the course of wetting is a fundamental phenomenon of nature. Dynamic wetting processes have a direct impact on flows at the nanoscale, and therefore, understanding them is exceptionally important to emerging technologies. Here, we reveal the microscopic mechanism of dynamic contact angle generation. It has been demonstrated using large-scale molecular dynamics simulations of bead-spring model fluids that the main cause of local contact angle variations is the distribution of microscopic force acting at the contact line region. We were able to retrieve this elusive force with high accuracy. It has been directly established that the force distribution can be solely predicted on the basis of a general friction law for liquid flow at solid surfaces by Thompson and Troian. The relationship with the friction law provides both an explanation of the phenomenon of dynamic contact angle and a methodology for future predictions. The mechanism is intrinsically microscopic, universal, and irreducible and is applicable to a wide range of problems associated with wetting phenomena.


Improving inter-rater reliability of the enhancing assessment of common therapeutic factors (ENACT) measure through training of raters.
As evidence supports task-shifting approaches to reduce the global mental health treatment gap, counselor competency evaluation measures are critical to ensure evidence-based therapies are administered with quality and fidelity. This article describes a training technique for evaluating lay counselors' competency for mental health lay practitioners without rating scale experience. Mental health practitioners were trained to give the Enhancing Assessment of Common Therapeutic Factors (ENACT) test to assess counselor proficiency in delivering the Common Elements Treatment Approach (CETA) in-person and over the phone using standardized video and audio recordings. A two-day in-person training was followed by a one-day remote training session. Training includes a review of item scales through didactic instructions, active learning by witnessing and scoring role-plays, peer interactions, and trainer observation and feedback. The trainees rated video and audio recordings, and ICC values were calculated. The training technique presented in this research helped achieve high counselor competency scores among lay providers with no prior experience using rating scales. ICC rated both trainings satisfactory to exceptional (ICC: .71 - .89). Raters with no past experience with rating scales can achieve high consistency when rating counselor competency through training. Effective rater training should include didactic learning, practical learning with trainer observation and feedback, and video and audio recordings to assess consistency.


Efficient amplification of a femtosecond Ti:sapphire laser with a ring regenerative amplifier.
A high-stability and high-efficiency ring Ti:sapphire regenerative amplifier is demonstrated based on a double-gating pulse picker at a repetition rate of 1 kHz. Pulse energy up to 5.7 mJ is obtained using a pump energy of 20.0 mJ at 527 nm, corresponding to a relatively high slope efficiency of 30.3%. After a grating compressor, the laser pulse is compressed to 37.2 fs with an energy of 4.1 mJ. The beam quality factors M(2) are 1.4 and 1.3 in tangential and sagittal directions, respectively. The measured root mean square energy stability is better than 0.31% over an 11 h period.


Japanese quail (Coturnix japonica) liver and thyroid gland histopathology as a result of in ovo exposure to the flame retardants tris(1,3-dichloro-2-propyl) phosphate and Dechlorane Plus.
Japanese quails (Coturnix japonica) were exposed in ovo to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP; 500 ng/µl), Dechlorane Plus (DP; 500 ng/µl), or a 1:1 mixture of these two to investigate the effects on liver and thyroid gland morphology. Histological examination of 14-day-old quails showed that exposure to TDCIPP or the mixture induced hepatic sinusoidal dilatation. No marked effects were seen for DP alone. In addition, the mixture produced divergence of thyroid gland follicles and proliferation of follicular cells. Our study is the first demonstrating histopathological alterations as a result of exposure during early development to the flame retardants TDCIPP or a TDCIPP-DP mixture suggesting the need for further research efforts to investigate potential adverse health effects associated with exposure to these environmental chemicals in wild birds.


Madhusudan Gupta.
Madhusudan Gupta (1800-1856) hailed from a high family. He joined the newly created Ayurvedic classes in Sanskrit College, Calcutta in 1926 [1826] and was promoted to the post of a teacher in the same medical college in view of his great interest and enthusiasm. He was the first man who dissected cadaver in 1936 [1836] and created a sensation in the orthodox Hindu Society. Madhusudan made a consistent effort for the improvement of medical science in India. A summary of the salient features of Madhusudan and his activities is presented in this paper with extracts of original passages appearing in reports of different committees and works.


KIAA0101 in Malignant Pleural Mesothelioma: A Potential Diagnostic and Prognostic Marker.
Currently, there are no reliable diagnostic and prognostic markers for Malignant Pleural Mesothelioma (MPM). The objective of this study was to identify hub genes that could be helpful for diagnosis and prognosis in MPM by using bioinformatics analysis. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Weighted Gene Co-expression Network Analysis (WGCNA), LASSO regression analysis, Cox regression analysis, and Gene Set Enrichment Analysis (GSEA) were performed to identify hub genes and their functions. A total of 430 upregulated and 867 downregulated genes in MPM were identified based on the GSE51024 dataset. According to the WGCNA analysis, differentially expressed genes were classified into 8 modules. Among them, the pink module was most closely associated with MPM. According to genes with GS > 0.8 and MM > 0.8, six genes were selected as candidate hub genes (NUSAP1, TOP2A, PLOD2, BUB1B, UHRF1, KIAA0101) in the pink module. In the LASSO model, three genes (NUSAP1, PLOD2, and KIAA0101) were identified with non-zero regression coefficients and were considered as hub genes among the 6 candidates. The hub gene-based LASSO model can accurately distinguish MPM from controls (AUC=0.98). Moreover, the high expression level of KIAA0101, PLOD2, and NUSAP1 was associated with poor prognosis compared to the low level in Kaplan-Meier survival analyses. After further multivariate Cox analysis, only KIAA0101 (HR = 1.55, 95% CI = 1.05-2.29) was identified as an independent prognostic factor among these hub genes. Finally, GSEA revealed that high expression of KIAA0101 was closely associated with 10 signaling pathways. Our study identified several hub genes relevant to MPM, including NUSAP1, PLOD2, and KIAA0101. Among these genes, KIAA0101 appears to be a useful diagnostic and prognostic biomarker for MPM, which may provide new clues for MPM diagnosis and therapy.


[An experimental study of using porcine small intestinal submucosa to repair rat full skin defect].
To investigate the feasibility of using the porcine small intestinal submucosa (SIS) as a kind of the new tissue engineered materials to repair the rat full skin defect. Twenty-eight 6-week-old SD rats weighing 300-350 g were selected in this experimental study. Two 2-cm-diameter round full skin defects were made on the rat back. The upper round defect was used as the blank group, which had no coverings, and the lower round defect was used as the SIS group. SIS that had been produced earlier was transplanted in the defected area. At 3 days, 1, 2, 3, 4, 6 and 8 weeks after the transplantation, the observation was made on the repaired skin conditions, the HE stain, and the repaired skin proportion. There was no infection in the two groups. The repairing speed in the SIS group was faster than that in the blank group at 2, 3, 4 and 6 weeks after the transplantation. The skin repaired by SIS was soft and elastic in texture, which had the same high level as the normal skin. The scar tissues in the SIS group were thinner than those in the blank group. The repaired skin proportions at 1, 2, 3, 4, 6 and 8 weeks after the transplantation were 15.72%+/-3.64%, 43.81%+/-4.87%, 65.35%+/-5.63%, 87.95%+/-4.78%, 96.90%+/-6.89% and 100%, respectively in the SIS group, and 13.42%+/-5.63%, 58.74%+/-4.48%, 76.50%+/-5.23%, 92.30%+/-5.75% and 100%, respectively in the blank group. There was a statistically significant difference between the two groups at 1, 2, 3 and 4 weeks after the transplantation (P<0.05). Under the microscope, the SIS-repaired skin was observed to have more keratinocytes and collagen tissues, which was familiar to the normal skin. Porcine SIS can be used as a new kind of the tissue engineered materials to repair the full skin defect.


A polymorphism in the CYP17 gene relates to the risk of recurrent pregnancy loss.
The CYP17 gene encodes the enzyme cytochrome P450c17alpha, which mediates both 17alpha-hydroxylase and 17,20-lyase activity in the steroid biosynthesis pathway. A T-->C polymorphism in the 5' promoter region of CYP17 has been described. To examine the association between recurrent pregnancy loss (RPL) and a polymorphism in CYP17, a case-control study of 117 cases with RPL and 164 controls was conducted. This polymorphism was investigated by PCR/restriction fragment length polymorphism using DNA from peripheral lymphocytes. The T-->C transition in the variant allele (A2) creates a new recognition site for the restriction enzyme MspA1, which permits designation of the wildtype allele (A1) and A2. Women with the A2 allele of CYP17 had an increased risk of RPL [A1/A1 genotype (reference); A1/A2 genotype: odds ratio (OR), 1.68; 95% confidence interval (CI), 0.94-3.01; A2/A2 genotype: OR, 2.37; 95% CI, 1.16-4.83; P trend, 0.016]. Additionally, there was a similar tendency for the increased risk of primary RPL [A1/A1 genotype (reference); A1/A2 genotype: OR, 2.14; 95% CI, 1.14-4.01; A2/A2 genotype: OR, 2.50; 95% CI, 1.16-5.41; P trend, 0.015]. These results suggest that possession of the A2 variant of CYP17 may predispose to an increased risk of RPL with a gene dosage effect.


Confounding by time since hire in internal comparisons of cumulative exposure in occupational cohort studies.
We use a simple, empirical model to describe the healthy worker effect mortality pattern. Under this simple model, internal comparisons of risk with increasing cumulative exposure will tend to be biased away from the null because of the healthy worker effect. We illustrate the potential magnitude of the bias in a simple situation and show that controlling for time since hire, by means of standard epidemiologic methods, eliminates the bias. Time since hire also is a concern of occupational epidemiologists because of the issue of induction time; sufficient time may not have elapsed among recently hired workers for an exposure to manifest its effect on disease occurrence. Provision for an adequate induction period can be addressed, like the concern raised in this paper, by restricting the analysis to workers first employed many years before the start of the follow-up period.


Krüppel-Like Factor 15 Mediates Glucocorticoid-Induced Restoration of Podocyte Differentiation Markers.
Podocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the podocyte, independent of the immunomodulatory effects, may lead to the identification of targets downstream of glucocorticoids that minimize toxicity without compromising efficacy. Several studies showed that treatment with glucocorticoids restores podocyte differentiation markers and normal ultrastructure and improves cell survival in murine podocytes. We previously determined that Krüppel-like factor 15 (KLF15), a kidney-enriched zinc finger transcription factor, is required for restoring podocyte differentiation markers in mice and human podocytes under cell stress. Here, we show that in vitro treatment with dexamethasone induced a rapid increase of KLF15 expression in human and murine podocytes and enhanced the affinity of glucocorticoid receptor binding to the promoter region of KLF15 In three independent proteinuric murine models, podocyte-specific loss of Klf15 abrogated dexamethasone-induced podocyte recovery. Furthermore, knockdown of KLF15 reduced cell survival and destabilized the actin cytoskeleton in differentiated human podocytes. Conversely, overexpression of KLF15 stabilized the actin cytoskeleton under cell stress in human podocytes. Finally, the level of KLF15 expression in the podocytes and glomeruli from human biopsy specimens correlated with glucocorticoid responsiveness in 35 patients with minimal change disease or primary FSGS. Thus, these studies identify the critical role of KLF15 in mediating the salutary effects of glucocorticoids in the podocyte.


Date-prints on stranded macroplastics: Inferring the timing and extent of overwash deposition on the Skallingen peninsula, Denmark.
The presented study shows that the delivery of marine macrodebris to a high-energy coastal environment has been abundant enough over the last three decades as to allow a spatial reconstruction of morphological change based on production-date prints. A dataset of >110 spatially discrete samples has been collected in an area affected by overwashing on the Skallingen peninsula, SW Denmark. A conceptual model for the chronological interpretation of the date prints is proposed and cross-compared with a dense time-series of satellite images and orthophotos. It appears that the litter-derived ages are capable of reproducing information on both the timing and the extent of overwash occurrence. Despite the usefulness of the method as a tool for rapidly assessing the approximate age of recent coastal deposits, the study shows the alarming degree and long-standing of marine-litter pollution on the eastern board of the southern North Sea.


Diabetic hypertensive leptin receptor-deficient db/db mice develop cardioregulatory autonomic dysfunction.
Leptin receptor-deficient db/db mice develop human type 2 diabetes mellitus, hypertension, and obesity with disrupted circadian blood pressure (BP) rhythm. Whether leptin is the sole mechanism mediating autonomic imbalance and hypertension is unclear. To explore this notion further, we measured BP by radiotelemetry combined with fast Fourier transformation and assessed autonomic function pharmacologically before and after renin-angiotensin system blockade with enalapril. The resting period BP (117+/-3 versus 108+/-1.0 mm Hg) and heart rate (HR; 488+/-12 versus 436+/-8 bpm) were higher in db/db mice compared with db/+ mice. BP and HR amplitudes were lower in db/db mice compared with db/+ mice. BP response to trimetaphan (-43+/-5 versus -27+/-3 mm Hg) and HR response to metoprolol (-59+/-12 versus -5+/-4 bpm) were greater in db/db mice than in db/+ mice. The HR response to atropine was blunted in db/db mice (59+/-17 versus 144+/-24 bpm), as were baroreflex sensitivity and HR variability. Enalapril improved autonomic regulation in db/db mice. Stimulation of central alpha-2 adrenoreceptors enhanced both parasympathetic HR control and baroreflex sensitivity in db/db mice. We suggest that functional, rather than structural, alpha-2 adrenoceptor changes and the renin-angiotensin system are involved in the increased sympathetic and decreased parasympathetic tones in db/db mice. Our data suggest that db/db mice exhibit features found in humans with type 2 diabetic autonomic neuropathy and could serve as a model for this complication.


Tandem Catalytic Indolization/Enantioconvergent Substitution of Alcohols by Borrowing Hydrogen to Access Tricyclic Indoles.
An efficient tandem catalysis method is achieved for the direct conversion of alcohol-containing alkynyl anilines to valuable chiral 2,3-fused tricyclic indoles. This method relies on a tandem indolization followed by enantioconvergent substitution of alcohols via borrowing hydrogen to construct two rings in one step, enabled by relay and cooperative catalysis of a chiral iridium complex with a chiral phosphoric acid. Highly diastereoselective transformations of the tricyclic indole products also provide efficient access to a diverse array of complex polycyclic indoline compounds.


Ultrasound-guided characterization of interstitial ablated tissue using RF time series: feasibility study.
This paper presents the results of a feasibility study to demonstrate the application of ultrasound RF time series imaging to accurately differentiate ablated and nonablated tissue. For 12 ex vivo and two in situ tissue samples, RF ultrasound signals are acquired prior to, and following, high-intensity ultrasound ablation. Spatial and temporal features of these signals are used to characterize ablated and nonablated tissue in a supervised-learning framework. In cross-validation evaluation, a subset of four features extracted from RF time series produce a classification accuracy of 84.5%, an area under ROC curve of 0.91 for ex vivo data, and an accuracy of 85% for in situ data. Ultrasound RF time series is a promising approach for characterizing ablated tissue.


[Effect of enflurane (ethrane) on intracranial pressure in comparison with halothane (author's transl)].
Enflurane (Ethrane) was given before operation to 13 neurosurgical patients. 11 of them received halothane for comparison of effects on intracranial pressure (ventricular catheter), blood pressure and central venous pressure during controlled ventilation. Neuroleptanalgesia was used as basic anaesthesia. The results showed that enflurane, when initial pressure levels were between 0-20 mm Hg, had better properties with regard to intracranial pressure than halothane. The intracranial pressure of 6 patients under enflurane rose. Of the remaining patients pressure did not change or even fell. Under halothane, given in a comparable doses, there was always a marked increase of intracranial pressure. If intracranial pressure of one patient under enflurane rose, then the increase by halothane always was more pronounced. The results from 1 patient had to be excluded because of spontaneously occurring plateau waves. Blood pressure was lowered by both agents while central venous pressure remained unchanged.