[Effects of different doses of levodopa on paraquat-induced neurotoxicity: an experiment with mice].
To investigate the effects and mechanisms of different doses of levodopa on paraquat-induced neuro-toxicity. 72 C57BL mice were divided into 2 equal groups: acute experiment group and chronic experiment groups. The acute experiment group was re-divided into 2 subgroup: subgroup A to be injected with levodopa of the doses of 0 (distilled water instead), 10 mg/kg, or 100 mg/kg and then paraquat 30 mg/kg (levodopa + paraquat), and then killed 90 minutes after; and subgroup B, to be injected with paraquat 30 mg/kg and then levodopa 0, 10 mg/kg, or 100 mg/kg (paraquat + levodopa), and then killed 2 hours after. The chronic experiment group was re-divided into 2 subgroups to be injected with levodopa + paraquat or paraquat + levodopa once a week for 3 weeks, and then killed 24 hours after the injection. Fluorescent microscopy was used to observe the fluorescent staining of paraquat in the substantia nigra in the acute experiment group and the fluorescent staining of tyrosine hydroxylase (TH) in the substantia nigra in the chronic experiment group. in the chronic experiment group Western blotting was used to examine the protein expression of TH; thioflavine double labeling was used to observe the alpha-synuclein aggregation by immunofluorescence staining and Western blotting. The slices of substantia nigra of the mice in the chronic experiment group treated with distilled water + paraquat were inoculated with or without 250 micromol/L levodopa and then underwent thioflavine staining to observe the alpha-Syn aggregation. The paraquat staining was strongly positive in the substantia nigra of the mice in Group A-1, and was decreased gradually in the group A-2 and A-3. The paraquat staining was strongly positive in the substantia nigra of Group B-1 without a significant difference between Group A-1 and Group B-1, and was not remarkable in Group B-2 and B-3. The TH staining and protein expression in the substantia nigra of Group A-2 were significantly stronger than that of Group A-1 (P < 0.05), and the TH staining was remarkably weaker in Group A-3 (P < 0.05), as shown by immunofluorescence staining and Western blotting. There was no significant difference in TH staining and protein expression in the substantia nigra among Group A-1, Group B-1, and Group B-2 (all P > 0.05). However, the TH staining was remarkably weaker in Group B-3 (P < 0.05). The thioflavine and alpha-Syn double staining was significantly weaker in Groups A-2 and A-3 in comparison with Group A-1. There was no significant difference in the double staining among Group A-1, Group B-1, and Group B-2 (all P > 0.05). However, the double staining was remarkably weaker in Group B-3 (P < 0.05). The thioflavine positive staining in the tissue slices inoculated with levodopa was significantly weaker in comparison with those un-inoculated. Pre-treatment with lower dose L-dopa before the paraquat administration is neuroprotective by preventing paraquat from access into central nervous system through a blood-brain barrier competitive uptake mechanism, while higher dose L-dopa shows neurotoxicity through disaggregating alpha-synuclein deposits in Parkinsonian mice.


Effect of topical application of doxycycline on pulp revascularization and periodontal healing in reimplanted monkey incisors.
Maxillary incisors in 47 monkeys, 54 in the experimental group (I) and 117 in the control group (II), were extracted and reimplanted, either immediately or after 30 or 60 min wet or dry storage. Incisors in the experimental group I were additionally kept 5 min in a suspension of 1 mg doxycycline in 20 ml physiologic saline, freshly prepared for each of the 15 animals before reimplantation. The observation time varied from 6 to 8 weeks. The teeth were removed in tissue blocks, histologically processed and evaluated for occurrence of complete pulp revascularization (CPR), presence of the micro-organisms in the pulpal lumen and ankylosis or inflammatory root resorption. Then the results were statistically evaluated, using log-linear analyses and chi-square tests (SAS, 1985) for the comparisons between group I and group II. These analyses revealed that topical application of doxycycline increased the frequency of complete pulp revascularization (P less than 0.002) and decreased the frequency of micro-organisms in the pulpal lumen (P less than 0.001). Furthermore, the frequencies of ankylosis (P less than 0.05) and inflammatory root resorption (P less than 0.001) were also decreased compared with the control group of teeth. It was concluded that the effect of topical treatment with doxycycline was most probably exerted on the micro-organisms that contaminated root surface during the extra-alveolar time; contamination of necrotic pulp tissue from the mechanical damage in the cervical part of the root surface was not affected.


Preparation of Block Copolymer Nano-Objects with Embedded β-Ketoester Functional Groups by Photoinitiated RAFT Dispersion Polymerization.
Herein, a photoinitiated reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of 2-(acetoacetoxy)ethyl methacrylate (AEMA) in ethanol/water at room temperature for in situ preparation of β-ketoester-functionalized block copolymer nano-objects is reported. AEMA is also copolymerized with isobornyl methacrylate (IBOMA) to improve the colloidal stability of PIBOMA-based block copolymer nano-objects prepared by photoinitiated RAFT dispersion polymerization at low temperatures. A series of P(IBOMA-stat-AEMA)-based block copolymer nano-objects are prepared by changing reaction parameters. Finally, lanthanide-doped block copolymer nano-objects with luminescent and magnetic properties are also prepared based on the complexation of various lanthanide ions with the β-ketoester group. It is expected that the current study will provide a facile platform for the in situ preparation of β-ketoester-functionalized block copolymer nano-objects with different morphologies for specific applications.


Effects of theabrownin from pu-erh tea on the metabolism of serum lipids in rats: mechanism of action.
Theabrownin (TB), one of the main bioactive components in pu-erh tea, has a significant blood lipid-lowering effect in hyperlipidemic rats. Therefore, it was hypothesized that TB would regulate the activity of key enzymes involved in lipid metabolism and accelerate the catabolism of exogenous cholesterol in rats fed a high fat diet. A total of 90 Sprague-Dawley rats were randomly divided into a normal control group (Group I), a high fat diet group (Group II), and high-fat diet plus TB group (Group III). A total of 10 rats were selected from each group and killed at 15, 30, or 45 d after starting the study for analysis. After feeding 45 d, the contents of TC, TG, and LDL-C levels in Group II were increased by 54.9%, 93.1%, and 134.3% compared with those in Group III, respectively, and the content of HDL-C in Group II was decreased by 55.7%. These effects were inhibited in the rats in Group III, which exhibited no significant differences in these levels compared with Group I, indicating that TB can prevent hyperlipidemia in rats fed a high fat diet. TB enhanced the activity of hepatic lipase and hormone-sensitive triglyceride lipase (HSL) and increased the HSL mRNA expression in liver tissue and epididymis tissue. The HL activity in serum of Group III was increased by 147.6% compared with that in Group II. The content of cholesterol and bile acid in the feces of rats was increased by 21.11- and 4.08-fold by TB. It suggested that TB could promote the transformation and excretion of dietary cholesterol of rats in vivo.


Solvated electron formation from the conduction band of liquid methanol: Transformation from a shallow to deep trap state.
We report solvated electron (esolv -) formation dynamics from the conduction band of liquid methanol studied using femtosecond time-resolved photoelectron spectroscopy. Liquid methanol is excited with vacuum UV (9.3 eV) pump pulses, and the subsequent electron dynamics are probed with UV pulses. The photoelectron signal exhibits a short-lived component (τ = 85 fs) without spectral evolution followed by a long-lived component with continuous spectral evolution over tens of picoseconds. We ascribe the former to a superexcited state, most likely the Wannier exciton, and the latter to the ground electronic state of esolv -. In order to extract accurate energetics from the observed photoelectron spectra, we employ a spectral retrieval method to account for spectral broadening and shifting due to inelastic scattering of photoelectrons in the liquid. The electron binding energy (eBE) of the initial trap state of an electron is determined to be about 1.5 eV, and its biexponential increase up to 3.4 eV is observed with time constants of 2 and 31 ps, which are greater than 0.27 and 13 ps observed for esolv - created by the charge-transfer-to-solvent reaction from CH3O- to liquid methanol. The solvation dynamics of esolv - created by the electron trapping exhibit a pseudoisosbestic point at a pump-probe delay time of around 15 ps, and the peak energy of the eBE distribution rapidly changes around that time. These results indicate that there exist two trap states, both of which exhibit increasing eBE with time; however, the eBE of the shallow trap state increases only up to 2.1 eV, and transformation to a deep trap state at 25 ps occurs to reach an eBE of 3.4 eV.


Perfusion-related parameters in intravoxel incoherent motion MR imaging compared with CBV and CBF measured by dynamic susceptibility-contrast MR technique.
Perfusion-related parameters obtained by intravoxel incoherent motion (IVIM) MR imaging (MRI) were compared with cerebral blood volume and flow (CBV and CBF), retrieved by dynamic susceptibility-contrast (DSC) MRI. Twenty-eight volunteers (average age 68.5 years) were investigated. Spin-echo echo-planar imaging with IVIM-encoding gradients was employed (36 different b values, 0-1200 s/mm2). The perfusion fraction and the pseudo-diffusion coefficient were calculated for regions in thalamus gray matter and frontal white matter, using asymptotic and full fitting. In DSC-MRI, a Gd-DTPA-BMA contrast-agent bolus was monitored using simultaneous-dual FLASH. Deconvolution of the measured tissue concentration-versus-time curve with an arterial input function from the carotid artery was applied, and maps of CBV and CBF were calculated. The correlation between the perfusion fraction and CBV was r=0.56 (p<0.0000006) using asymptotic fitting, and r=0.35 (p<0.0004) when full fitting was applied. Average CBF was 41.5 ml/(min 100 g), to be compared with the IVIM-based value of 63.6 ml/(min 100 g), obtained from the median value of the pseudo-diffusion coefficient in combination with assumptions about capillary network structure. The IVIM concept provided results that agreed reasonably with conventional CBV and CBF. The non-linear fitting to noisy signal data was problematic, in accordance with previously presented simulations.


A semiclassical correction for quantum mechanical energy levels.
We propose a semiclassical method for correcting molecular energy levels obtained from a quantum mechanical variational calculation. A variational calculation gives the energy level (i.e., eigenvalue) as the expectation value of the molecular Hamiltonian <phi/H/phi>, where /phi> is the trial wave function. The true (i.e., exact) eigenvalue E can thus be expressed as this variational result plus a correction, i.e., E=<phi/H/phi>+DeltaE, the correction being due to the lack of exactness of the trial wave function. A formally exact expression for DeltaE is usually given (via Löwdin partitioning methodology) in terms of the Greens function of the Hamiltonian projected onto the orthogonal complement of /phi>. Formal treatment of this expression (using Brillouin-Wigner perturbation theory to infinite order) leads to an expression for DeltaE that involves matrix elements of the Greens function for the unprojected, i.e., full molecular Hamiltonian, which can then be approximated semiclassically. (Specifically, the Greens function is expressed as the Fourier transform of the quantum mechanical time evolution operator, e(-iHt/variant Planck's over 2pi), which in turn is approximated by using an initial value representation of semiclassical theory.) Calculations for several test problems (a one dimensional quartic potential, and vibrational energy levels of H(2)O and H(2)CO) clearly support our proposition that the error in the total eigenvalue E arises solely due to the semiclassical error in approximating DeltaE, which is usually a small fraction of the total energy E itself.


[Analysis of the outcome of the treatment of small bowel obstruction and factors which determine the outcome (10-year experience at the Kaunas Medical University Clinic)].
To evaluate the results of the treatment of small bowel obstruction in the Surgical clinic of Kaunas University of Medicine in 1990-1999, the changes of the results of the treatment, to evaluate the factors, which determine these changes. 489 patients with small bowel obstruction (SBO) were treated during 10-year period. Acute SBO was found in 433 (88.5%) cases; 322 (65.8%) patients underwent surgery. The patients were divided into two groups: 1990-1995 year group (A) and 1996-1999 year group (B) according to the newly implemented methods of diagnostics and treatment (computer-aided diagnosis, laparoscopic cutting of adhesions, conservative small bowel decompression with long intestinal tube and etc.). Both groups were statistically similar. By means of statistical methods factors, which determine the results of the treatment of SBO, were found and the differences of distribution of these factors in both groups were evaluated. The mortality rate was 10.3% in group A and 1.8%--in group B. The most significant factors, which determine the outcome of the treatment of SBO, were: the time period of making diagnosis, adjacent illnesses, small bowel necrosis and its length, acute SBO, SBO due to multiple adhesions, surgical methods. In comparing both groups, they differed according to the time of making diagnosis (18.6 h and 9.6 h), the frequency of small bowel necrosis (14.2% and 5.7% cases); the methods of surgery also differed. The results of the treatment of SBO improved. The short-cut of the time period to make diagnosis, the more rare cases of bowel necrosis and new surgical methods influenced these changes.


U.K. National Radiological Protection Board Radon Calibration Procedures.
A procedure for the calibration of instruments for the detection of 222Rn in air is described. The method is based on the alpha-spectrometric determination of the concentration in air of 218Po in the calibration chamber. The calibration chamber is described, together with the method of maintaining a high aerosol concentration. The 218Po concentration at steady state in the chamber is found to be 98% of the 222Rn concentration typically. An assessment of the sources of uncertainty in the method presented indicate that the 222Rn concentration in the chamber can be determined with an overall uncertainty of about 7% at the 95% confidence level.


Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis.
Recent advances have led to novel identification of genetic polymorphisms that are associated with susceptibility to rheumatoid arthritis (RA). Currently, 5 loci (HLA, PTPN22, TRAF1/C5, TNFAIP3, and STAT4) have been consistently reported, whereas others have been observed less systematically. The aim of the present study was to independently replicate 3 recently described RA susceptibility loci, STAT4, IL2/IL21, and CTLA4, in a large Dutch case-control cohort, and to perform a meta-analysis of all published studies to date and investigate the relevance of the findings in clinically well-defined subgroups of RA patients with or without autoantibodies. The STAT4, IL2/IL21, and CTLA4 gene polymorphisms (rs7574865, rs6822844, and rs3087243, respectively) were genotyped in 877 RA patients and 866 healthy individuals. A meta-analysis of all published studies of disease association with these polymorphisms was performed using the Mantel-Haenszel fixed-effects method. An association of STAT4, IL2/IL21, and CTLA4 with RA was detected in Dutch patients (odds ratio [OR] 1.19 [P=0.031], OR 0.84 [P=0.051], and OR 0.87 [P=0.041], respectively). Results from the meta-analysis confirmed an association of all 3 polymorphisms with RA in Caucasians (OR 1.24 [P=1.66x10(-11)], OR 0.78 [P=5.6x10(-5)], and OR 0.91 [P=1.8x10(-3)], respectively). The meta-analysis also revealed that STAT4 predisposed to disease development equally in patients with autoantibodies and those without autoantibodies, and that CTLA4 enhanced the development of anti-citrullinated protein antibody (ACPA)-positive RA as compared with ACPA-negative RA. Our results replicate and firmly establish the association of STAT4 and CTLA4 with RA and provide highly suggestive evidence for IL2/IL21 loci as a risk factor for RA. Given the strong statistical power of our meta-analysis to confirm a true-positive association, these findings provide considerable support for the involvement of CTLA4 in distinct subsets of RA patients.


Effects of teneligliptin on PDMPs and PAI-1 in patients with diabetes on hemodialysis.
Cardiovascular disease (CVD) is the main cause of death among hemodialysis (HD) patients. The effects of the dipeptidyl peptidase-4 inhibitor teneligliptin on CVD-related biomarkers in patients with type 2 diabetes mellitus (T2DM) receiving HD treatment are poorly understood. To determine whether teneligliptin has anti-CVD properties, we assessed its effects on soluble P-selectin (sP-selectin), platelet-derived microparticles (PDMPs), plasminogen activator inhibitor 1 (PAI-1), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule 1 (sVCAM-1), and adiponectin plasma levels in HD and non-HD patients with T2DM. Patients with T2DM eligible for teneligliptin monotherapy or combination therapy (eg, teneligliptin plus a sulfonylurea) were administered teneligliptin (20 mg/d) once daily for 6 months. Plasma levels of sP-selectin, PDMPs, PAI-1, sE-selectin, sVCAM-1, and adiponectin were measured by enzyme-linked immunosorbent assay at baseline and after 3 months and 6 months of treatment. Teneligliptin therapy significantly reduced plasma levels of sP-selectin, PDMPs, and PAI-1 compared with baseline levels, while significantly increasing adiponectin levels. sE-selectin and sVCAM-1 levels were significantly decreased only at 6 months. The reduction in sP-selectin, PDMPs, and PAI-1 was more significant in HD patients than in non-HD patients. However, the improvement in adiponectin levels was unchanged with HD treatment. By modulating PDMPs or PAI-1, teneligliptin shows an antiatherothrombotic effect that may be beneficial in the primary prevention of CVD in patients with T2DM on HD.


Selective and sensitive colorimetric detection of stringent alarmone ppGpp with Fenton-like reagent.
Stringent alarmone, namely, guanosine 3'-diphosphate-5'-diphosphate (ppGpp), is a global regulator that plays a critical role in the survival, growth, metabolism, and many other vital processes of microorganisms. Because of its structural similarity to normal nucleotides, it is also a challenge for the selective and sensitive detection of ppGpp nowadays. Herein, we developed a colorimetric method for the selective detection of ppGpp by inhibiting the redox reaction between Fenton-like reagent (composed of Fe(3+) and H2O2) with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS). Owing to the strong coordination affinity between ppGpp and Fe(3+), the chromogenic reaction between ABTS and Fenton-like reagent, occurred in aqueous medium at 37 °C and resulted in a bluish-green solution, which was inhibited with the addition of ppGpp. This phenomenon forms the basis for the colorimetric detection of ppGpp, with a detection limit of 0.19 μM and good selectivity for ppGpp over other nucleotides and anions. Furthermore, the results could be visualized by the naked eye, and the sensitivity of the naked-eye observation could even be further improved with the aid of the introduction of a background color.


Use of herbal therapies to relieve pain: a review of efficacy and adverse effects.
To find holistic treatment with effective pain relief and few side effects, Americans spend billions of dollars annually on complementary and alternative medicine, including herbal therapies. Despite extensive use, the lack of regulatory scrutiny of these herbal supplements contributes to the paucity of reliable clinical data assessing their efficacy and safety. This review summarizes the existing studies investigating the efficacy of herbal therapies as a treatment for pain. Possible side effects, potential drug-herb interactions, and information about common herbal therapies are also summarized. MEDLINE, AMED, and the Cochrane Library databases were searched for the period from January 1966 to June 2005. Uses, dosages, routes of administration, and side effects were summarized. Strength of empirical evidence also was evaluated. This review found few well-controlled clinical studies. Furthermore, these studies documented limited efficacy of herbal therapies to treat pain. The information presented here may be used to further educate nurses and patients on the use of herbal therapies as well as direct future research efforts.


Dek35 Encodes a PPR Protein that Affects cis-Splicing of Mitochondrial nad4 Intron 1 and Seed Development in Maize.
In higher plants, the splicing of organelle-encoded mRNA involves a complex collaboration with nuclear-encoded proteins. Pentatricopeptide repeat (PPR) proteins have been implicated in these RNA-protein interactions. In this study, we performed the cloning and functional characterization of maize Defective kernel 35 (Dek35). The dek35-ref mutant is a lethal-seed mutant with developmental deficiency. Dek35 was cloned through Mutator tag isolation and further confirmed by four additional independent mutant alleles. Dek35 encodes an P-type PPR protein that targets the mitochondria. The dek35 mutation causes significant reduction in the accumulation of DEK35 proteins and reduced splicing efficiency of mitochondrial nad4 intron 1. Analysis of mitochondrial complex in dek35 immature seeds indicated severe deficiency in the complex I assembly and NADH dehydrogenase activity. Transcriptome analysis of dek35 endosperm revealed enhanced expression of genes involved in the alternative respiratory pathway and extensive differentially expressed genes related to mitochondrial function and activity. Collectively, these results indicate that Dek35 encodes an PPR protein that affects the cis-splicing of mitochondrial nad4 intron 1 and is required for mitochondrial function and seed development.


Genetic and functional analysis of single nucleotide polymorphisms in the beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2).
The beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2) is a logical candidate for influencing smoking behavior and nicotine dependence. We discovered six single nucleotide polymorphisms (SNPs) in the CHRNB2 gene by surveying 15.4 kb of genomic sequence including a previously undescribed 3' untranslated region that extends 4.0 kb downstream of the coding region. One of the SNPs causes an amino acid substitution in exon 5, one occurs in the promoter region, one changes an intronic base, and three occur in the 3' untranslated region. The ethnically dependent allele frequencies and the marker-to-marker linkage disequilibrium patterns of five of these polymorphisms were determined. The SNPs were assayed in 743 individuals for whom information on smoking history and lifelong nicotine dependence was available. No significant associations of the individual markers or their haplotypes to smoking behavior or level of nicotine dependence were found.


The microbial ecology of anaerobic cellulose degradation in municipal waste landfill sites: evidence of a role for fibrobacters.
Cellulose is reputedly the most abundant organic polymer in the biosphere, yet despite the fundamental role of cellulolytic microorganisms in global carbon cycling and as potential sources of novel enzymes for biotechnology, their identity and ecology is not well established. Cellulose is a major component of landfill waste and its degradation is therefore a key feature of the anaerobic microbial decomposition process. Here, we targeted a number of taxa containing known cellulolytic anaerobes (members of the bacterial genus Fibrobacter, lineages of Clostridium clusters I, III, IV and XIV, and anaerobic fungi of the Neocallimastigales) in landfill leachate and colonized cellulose 'baits' via PCR and quantitative PCR (qPCR). Fibrobacter spp. and Clostridium clusters III, IV and XIV were detected in almost all leachate samples and cluster III and XIV clostridia were the most abundant (1-6% and 1-17% of total bacterial 16S rRNA gene copies respectively). Two landfill leachate microcosms were constructed to specifically assess those microbial communities that colonize and degrade cellulose substrates in situ. Scanning electron microscopy (SEM) of colonized cotton revealed extensive cellulose degradation in one microcosm, and Fibrobacter spp. and Clostridium cluster III represented 29% and 17%, respectively, of total bacterial 16S rRNA gene copies in the biofilm. Visible cellulose degradation was not observed in the second microcosm, and this correlated with negligible relative abundances of Clostridium cluster III and Fibrobacter spp. (≤ 0.1%), providing the first evidence that the novel fibrobacters recently detected in landfill sites and other non-gut environments colonize and degrade cellulose substrates in situ.


Ethnic variation in vellus hair follicle size and distribution.
It is a given fact that hair follicles play an important role in the penetration process of topically applied drugs and cosmetics. Since exact knowledge of the potential follicular reservoir is essential for understanding and calculating the penetration process, this knowledge may indeed help to optimize the development of topically applied drugs and cosmetic products. We know that variability in skin properties exists among the human population, but it is the deciphering and quantification of these differences that may help to explain racial disparities in dermatological disorders and provide a basic approach for treatment and prevention. Data pertaining to structural and functional differences within ethnic skin types (reviewed in this paper) support the assumption that hair follicles in the various skin types are not equal. Thus, the need to investigate follicular morphology in non-Caucasian skin types becomes more than apparent. The aim of the present study was to determine the potential reservoir of vellus hair follicles in non-Caucasian skin types in order to estimate their contribution to the penetration of topically applied substances. Cyanoacrylate skin surface biopsies were taken from seven body sites of Asians and African-Americans. To determine the follicular reservoir, the samples were evaluated under the light microscope. Follicular parameters were measured with the help of a digital imaging software program. In the evaluation and comparison of the results with those of Caucasians, significant differences were detected. Compared with Whites, follicular density on the forehead is significantly lower in Asians and African-Americans. Smaller values were detected for volume, surface, follicular orifice and hair shaft diameter on the thigh and in calf regions in Asians and African-Americans. Furthermore, the follicular reservoir, characterized by follicular volume, is generally higher in Caucasians. In comparison to African-Americans, larger follicular volumes on the forehead, back and on the upper arm were determined in Asians. The fairly similar density in these sites revealed that Asians have a higher follicular reservoir in these sites. Due to significant ethnic differences in the follicular reservoir, particularly on the calf and forehead, prospective skin absorption experiments need to be performed on different skin types in order to be representative. Likewise, the development of topically applied drugs should take place under adequate consideration of ethnic differences in skin physiology.


Reconstruction of complex abdominal wall defects.
Complex abdominal wall defects refer to situations where simple ventral hernia repair is not feasible because the defect is very large, there is a concomitant infection or failed previous re-pair attempt, or if there is not enough original skin to cover the repair. Usually a complex abdominal wall repair is preceded by a period of temporary abdominal closure where the short-term aims include closure of the catabolic drain, protection of the viscera and preventing fistula formation, preventing bowel adherence to the abdominal wall, and enabling future fascial and skin closure. Currently the best way to achieve these goals is the vacuum- and mesh-mediated fascial traction method achieving close to 90% fascial closure rates. The long-term aims of an abdominal closure following a planned hernia strategy include intact skin cover, fascial closure at midline (if possible), good functional outcome with innervated abdominal musculature, no pain and good cosmetic result. The main methods of abdominal wall reconstruction include the use of prosthetic (mesh) or autologous material (tissue flaps). In patients with original skin cover over the fascial defect (simple ventral hernia), the most commonly used method is hernia repair with an artificial mesh. For more complex defects, our first choice of reconstruction is the component separation technique, sometimes combined with a mesh. In contaminated fields where component separation alone is not feasible, a combination with a biological mesh can be used. In large defects with grafted skin, a free TFL flap is the best option, sometimes reinforced with a mesh and enhanced with components separation.


Pseudocysts and other non-neoplastic cysts of the pancreas.
Among the cystic lesions of the pancreas, pseudocysts are most common. This article summarizes the current state of knowledge on the morphology and pathogenesis of pseudocysts. Specifically, the pathogenetic relationship between pancreatic pseudocysts and acute and chronic pancreatitis and the natural history of pseudocysts will be discussed. In addition, this article gives a brief description of a few non-neoplastic pancreatic cysts, including retention cysts, congenital cysts, cystic acinar transformation, para-ampullary duodenal wall cysts, enterogenous cysts, endometrial cysts, and parasitic cysts.


Post-transplant hyperglycaemia: a study of risk factors.
Post-transplant diabetes mellitus (PTDM) has several identifiable pre- and post-transplant risk factors. The link to nutritional status pre-transplant has not been explored previously. This study was conducted to identify risk factors for the development of PTDM, with emphasis on pre-transplant nutritional status and glucose tolerance. Non-diabetic adult end-stage renal failure patients awaiting renal transplantation were studied prospectively. Their nutritional status was assessed as body mass index (BMI), serum albumin, and the evolution of these parameters over time prior to transplantation. An oral glucose tolerance test (OGTT) was performed pre- and serially post-transplant until 6 months. Pre- and post-transplant risk factors such as age, nutritional status, glucose tolerance parameters and immunosuppression were related to the development of PTDM or impaired glucose tolerance (IGT) post-transplant. The mean age of 174 patients studied over a 2-year period was 32.9 +/- 9.7 years. The mean post-transplant follow-up was 25.6 +/- 12.8 months. The mean BMI at recruitment was 18.3 +/- 2.4 kg/m(2). The rate of increase in BMI pre-transplant showed an inverse correlation with the baseline BMI (r = -0.34, P = 0.000) and formed an independent marker of nutritional status. PTDM developed in 21.4% patients and 24.1% had IGT. On univariate and multivariate analyses, the factors significantly associated with the development of PTDM were greater age, more rapid increase in dry weight after starting haemodialysis (HD), elevated pre-transplant OGTT responses and cyclosporin (CsA) and prednisolone doses early post-transplant. Additionally, on multivariate analysis, higher CsA trough level > 300 ng/ml at 3 months increased the risk for the development of PTDM. Of patients who developed PTDM, 57% had impairment of glucose tolerance pre-transplant (> 140 mg/dl at 2 h). Patients with a 1-h glucose value greater than the 50th percentile on pre-transplant OGTT had a 3.9-fold greater risk for the development of PTDM (P = 0.05, 95% CI = 1.03-11.1). In those patients with higher 1-h glucose (> 50th percentile) who also gained in dry weight rapidly pre-transplant, the risk increased to 5.3 (P = 0.02). Of 76 patients with abnormal OGTT early post-transplant, only 68% continued to have PTDM or IGT post-transplant, the remainder reverting to normal glucose tolerance. Persistent abnormal glucose tolerance after transplantation was seen in 45% of the patients. Pre-transplant factors including greater age, abnormal glucose tolerance parameters, and rapid gain in dry weight on HD, along with higher prednisolone and CsA doses early post-transplant were the important factors associated with the development of PTDM. Identification of patients with pre-transplant risks might allow modification of post-transplant immunosuppression with non-diabetogenic agents.


Techniques to save the sea.
Ocean health has declined dramatically over the past few decades, threatening the rich biodiversity and ecosystem services the ocean provides. In this feature, we look at the life science techniques that could potentially save the sea.


Demonstration of CNOT gate with Laguerre Gaussian beams via four-wave mixing in atom vapor.
We present an experimental study of controlled-NOT (CNOT) gate through four-wave mixing (FWM) process in a Rubidium vapor cell. A degenerate FWM process in a two level atomic system is directly excited by a single diode laser, where backward pump beam and probe beam are Laguerre Gaussian mode. By means of photons carrying orbital angular momentum, we demonstrate the ability to realize CNOT gate with topological charges transformation in this nonlinear process. The fidelity of CNOT gate for a superposition state with different topological charge reaches about 97% in our experiment.


cAMP increases synthesis of surfactant-associated protein A by perfused rat lung.
Synthesis and secretion of surfactant-associated protein were studied in isolated rat lungs perfused with [3H]phenylalanine or [35S]methionine in synthetic medium. Surfactant was isolated by lung lavage and density-gradient centrifugation followed by dialysis to remove unincorporated amino acid and extraction with ethanol-ether to yield a delipidated protein fraction. Incorporation of [3H]phenylalanine into the delipidated surfactant protein fraction showed a lag phase of approximately 3 h followed by progressive increase over the next 3 h at a rate of 1.6 nmol.mg protein-1.h-1. With 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP, 0.1 mM) added to the perfusate, the incorporation rate between 3 and 6 h was increased by 75%. 3H specific activity in a delipidated lamellar body-rich fraction isolated from lung homogenates was unchanged by 8-BrcAMP at 3 h but was increased by 45% at 6 h. The major peak of radioactivity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of surfactant and lamellar bodies corresponded to proteins of 27-36 kDa that were identified as surfactant protein A (SP-A) by immunoblot. In the presence of 8-BrcAMP during 6 h of perfusion, specific activity of 35S-labeled SP-A in immunoprecipitated protein was increased by 93% and the SP-A mRNA content of lung was increased 145%. These results show that isolated perfused lungs synthesize and secrete surfactant-associated proteins and that the presence of a permeable cAMP analogue in the lung perfusate leads to increased secretion followed by induction of synthesis for SP-A.


Propagating nanocavity-enhanced rapid crystallization of silicon thin films.
We demonstrate a mechanism of solid-phase crystallization (SPC) enabled by nanoscale cavities formed at the interface between an hydrogenated amorphous silicon film and embedded 30 to 40 nm Si nanocrystals. The nanocavities, 10 to 25 nm across, have the unique property of an internal surface that is part amorphous and part crystalline, enabling capillarity-driven diffusion from the amorphous to the crystalline domain. The nanocavities propagate rapidly through the amorphous phase, up to five times faster than the SPC growth rate, while "pulling behind" a crystalline tail. Using transmission electron microscopy it is shown that twin boundaries exposed on the crystalline surface accelerate crystal growth and influence the direction of nanocavity propagation.


Multiple unusual lung etiologies in a child with acute lymphocytic leukemia.
Granulomatous lung disease is a rare and perplexing differential in pediatrics. Pulmonary Cryptococcus falls into the differential but is not high on the list, particularly in a non-AIDS patient. Methotrexate (MTX) is a commonly used agent for chemotherapy in oncology and has been documented to cause lung injury in both patients with rheumatologic and oncologic diseases. Our patient had chronic cough and then developed an opportunistic infection resulting in respiratory failure. Lung biopsy showed two underlying unusual diagnoses: MTX lung injury and cryptococcal pneumonia. His case is presented with particular attention to his prolonged road to diagnosis.


Host-integration of a tissue-engineered airway patch: two-year follow-up in a single patient.
Different bioengineering techniques have been applied repeatedly for the reconstruction of extensive airway defects in the last few years. While short-term surgical success is evident, there is a lack of long-term results in patients. Here, we report the case of a young male who received a 5×2 cm bioartificial airway patch for tracheoesophageal reconstruction focusing on clinical defect healing and histomorphological tissue reorganization 2.5 years after surgery. We generated bioartificial airway tissue using a cell-free biological vascularized scaffold that was re-endothelialized and reseeded with the recipient's autologous primary cells and we implanted it into the recipient's left main bronchus. To investigate host-integration 2.5 years after the implantation, we obtained biopsies of the implant and adjacent tracheal tissue and processed these for histological and immunohistochemical analyses. The early postoperative course was uneventful and the transplanted airway tissue was integrated into the host. 2.5 years after transplantation, a bronchoscopy confirmed the scar-free reconstruction of the former airway defect. Histological work-up documented respiratory airway mucosa lining the bronchial reconstruction, making it indistinguishable from native airway mucosa. After transplantation, our bioartificial airway tissue provided perfect airway healing, with no histological evidence of tissue dedifferentiation.


Reconstitution of prenyltransferase activity on nanodiscs by components of the rubber synthesis machinery of the Para rubber tree and guayule.
Natural rubber of the Para rubber tree (Hevea brasiliensis) is synthesized as a result of prenyltransferase activity. The proteins HRT1, HRT2, and HRBP have been identified as candidate components of the rubber biosynthetic machinery. To clarify the contribution of these proteins to prenyltransferase activity, we established a cell-free translation system for nanodisc-based protein reconstitution and measured the enzyme activity of the protein-nanodisc complexes. Co-expression of HRT1 and HRBP in the presence of nanodiscs yielded marked polyisoprene synthesis activity. By contrast, neither HRT1, HRT2, or HRBP alone nor a complex of HRT2 and HRBP manifested such activity. Similar analysis of guayule (Parthenium argentatum) proteins revealed that three HRT1 homologs (PaCPT1-3) manifested prenyltransferase activity only when co-expressed with PaCBP, the homolog of HRBP. Our results thus indicate that two heterologous subunits form the core prenyltransferase of the rubber biosynthetic machinery. A recently developed structure modeling program predicted the structure of such heterodimer complexes including HRT1/HRBP and PaCPT2/PaCBP. HRT and PaCPT proteins were also found to possess affinity for a lipid membrane in the absence of HRBP or PaCBP, and structure modeling implicated an amphipathic α-helical domain of HRT1 and PaCPT2 in membrane binding of these proteins.


A review of the Medical Agency Services Confor-Med range.
Medical Agency Services Ltd (MAS) has, since 1994, been involved in the design and development of mattresses and overlays manufactured from visco-elastic polymer foam, which is currently utilized in the manufacture of domestic, automative and specialist bedding and seating products. The foam is fire retardant and satisfies the BS 5852 (Part 2) ignition source 5. The foam is a heat and weight sensitive, visco-elastic polymer, giving a high performance, pressure redistributing surface that 'moulds' to the patient giving simultaneous muscular/skeletal support and allowing the patient to feel comfortable. The Confor-Med mattress offers a sensible alternative for patients with high Waterlow scores who have no pressure sores, but require early intervention to prevent pressure sores developing. A case study is included in this review of the products.


General Pavlovian-to-instrumental transfer in humans: Evidence from Bayesian inference.
When repeatedly paired with rewarding outcomes (i.e., Pavlovian conditioning), environmental cues may acquire predictive and motivational significance and later enhance instrumental responding for the same (i.e., outcome-specific transfer) or motivationally similar (i.e., general transfer) outcomes. Although outcome-specific and general Pavlovian-to-Instrumental Transfer (PIT) are characterized by different neural substrates and behavioral mechanisms, general transfer has never been studied in isolation from outcome-specific transfer in humans. The first aim of the present study was to test whether the general transfer effect could emerge in isolation and independently of outcome-specific transfer. Our results showed that general transfer can be elicited without the concurrent presence of outcome-specific transfer, supporting the idea that outcome-specific and general transfer can be studied independently of each other. The second aim of the present study was to clarify whether the affordance-like properties of the outcomes can affect the general transfer. In fact, a critical difference in current studies on general transfer concerns the use of cues associated with outcomes for which an action was previously learned (or not) during the instrumental training. This apparently minor difference affects the affordance-like properties of the outcome and may also be transferred to the cue, in turn impacting general transfer. Results revealed a general transfer of the same magnitude regardless of whether cues were associated with reward earned or not during instrumental conditioning. These findings increase the current knowledge on the incentive motivational mechanism behind general transfer, indicating that it is independent of the motor features of the outcome.


Physical training in Becker muscular dystrophy associated with heart failure.
Becker muscular dystrophy (BMD) integrates dystrophy occurring due to genetic mutations that express the dystrophin protein in chromosome X. The onset of neuromuscular symptoms usually precedes the impairment of cardiac function, and may conversely happen by heart failure (HF). Physical training is well established in HF, however, when combined with BMD, it is controversial and without any scientific basis. This study presents the case of a patient with BMD associated with HF in cardiac transplant waiting list undergoing a physical training program.


High-Frequency Induction Heated Synthesis and Consolidation of Nanostructured Al-TaC Composite and Its Mechanical Properties.
The significance of Al matrix composites reinforced with metal carbide having low density and very high hardness increases in order to reduce CO₂ emissions and improve the efficiency of energy in automobile and transportation industries. Nanopowder mixture of Ta and Al₄C₃ were fabricated by high energy ball milling. Highly dense nanostructured 4Al-3TaC composite was consolidated by high-frequency induction heated sintering within one min from the mechanically activated nanopowder mixture of Ta and Al₄C₃ under the 80 MPa pressure. The microstructure, sintering behavior and mechanical properties (hardness and fracture toughness) were evaluated using FE-SEM and Vickers hardness tester.


Complex neurologic syndrome associated with the G1606A mutation of mitochondrial DNA.
To confirm the pathogenicity of the G-to-A substitution at nucleotide 1606 (G1606A) mutation in the mitochondrial DNA (mtDNA) tRNA(Val) gene, and to characterize genotype-phenotype correlation. A 37-year-old man since childhood developed a complex clinical picture characterized by hearing loss, migraine, ataxia, seizures, cataracts, retinitis pigmentosa, mental deterioration, and hypothyroidism. Magnetic resonance imaging revealed diffuse calcification of the basal ganglia and cerebral cortical atrophy. Morphologic and biochemical studies of respiratory chain complexes were performed in skeletal muscle. All 22 mitochondrial tRNA genes were screened for mutations by direct sequencing. Biochemical analysis showed normal activities of respiratory chain enzymes and citrate synthase; morphologic examination showed scattered ragged-red fibers and poor or absent cytochrome c oxidase staining in 10% of the fibers. A heteroplasmic G1606A transition in the mtDNA tRNA(Val) gene was found. Mutant DNA was 70% of the total in the proband's muscle. The mutation was absent in blood samples and urinary sediment from his healthy brother and mother. This second patient with the G1606A mutation confirms both the pathogenicity of the mutation and its association with a characteristic complex neurologic phenotype.


IgM nephropathy in children: clinicopathologic analysis.
IgM nephropathy (IgMN) is a glomerulonephritis characterised by diffuse mesangial immunoglobulin M (IgM) deposits. It usually presents with nephrotic range proteinuria and, according to some previous work, it occurs most often in patients who are resistant to or dependent on steroid treatment. To perform a clinical, histological and immunopathological description and assess the response to steroid treatment of paediatric patients diagnosed with nephrotic syndrome and diffuse mesangial IgM deposits. This is a descriptive, retrospective study carried out in two hospitals, where the clinical records of paediatric patients with IgMN were analysed and the histological sections were re-assessed. thirteen children were included in this study. IgMN corresponded to 5.17% of all paediatric renal biopsies. The age of patients ranged from 1 year to 12 years (median: 2 years), 46.7% were women. The most common morphological finding was diffuse mesangial hypercellularity (46.1%), followed by focal segmental glomerulosclerosis (30.8%) and minimal glomerular changes (23.1%). All patients received steroids; in 4 cases (30.7%) as the only immunosuppressant medication, 3 (23.1%) also received cyclophosphamide, 5 (38.4%) mycophenolate, and 1 (7.7%) cyclosporine. Seven patients (53.8%) had frequent relapses, 5 (38.5%) were cortico-resistant and 1 (7.7%) cortico-dependent. Two patients (15.38%) had chronic impairment of renal function. The presence of diffuse mesangial IgM in paediatric patients with nephrotic syndrome is not a very uncommon finding; its clinical presentation has been associated with lower response to steroids. However, the long-term prognosis of these patients is still unknown.


[Psychic change in schizophrenic patients produced group therapy].
The objective of this paper is to analyze the effectiveness of group therapy to produce psychic change in patients with schizophrenia and other related psychosis. The experience took place in a Public Psychiatric Hospital. It involved 96 patients with this condition who entered different groups from 1998 up to the present. During the year 2000, 66 of them were asked to answer a questionnaire especially designed to investigate the changes that they thought they had gone through during this treatment. On one hand, the results show the high valorization of the group appliance, while on the other hand the most valued operational categories were the facilitation of interpersonal links, the valorization of listening and being listened, the recognition of improvement and the recognition of one's own characteristics in the other person. On account of these discoveries, the mechanisms of these group appliances to produce such changes are postulated. In conclusion, group treatment for schizophrenic patients and related psychosis turns out to be useful for producing psychic changes different from those achieved with psychopharmacological agents.


Receptor changes in metachronous breast tumors--our experience of 10 years.
Patients with primary breast cancer (PBC) are at 2 to 6 times higher risk for developing synchronous and metachronous breast cancer (MBC). The pathology and behavior of MBC still remains unclear. We reviewed the charts of 108 women with MBC at our hospital over the past 10 years. Profile patterns of the estrogen receptor (ER), the progesterone receptor (PR), and Her2/neu receptors were explored. Of 33 patients with ER(+)/PR(+) in the primary tumor, 23 (70%) retained the status in MBC. Forty-five (92%) of 49 patients with ER(-)/PR(-) in the primary tumor remained the same in MBC. Most Her2(-) tumors (22/31, 71%) remained negative, but 50% (8/16) of Her2(+) tumors became negative. Most MBC retained the ER/PR expression patterns irrespective of the treatment for the primary tumor, thus suggesting a common origin. Because MBCs tend to be triple negative and thus more aggressive, early detection and close surveillance techniques must be devised.


Diet and the kidney.
This is a short synopsis of the importance of nutrition and disease, which is especially centered on the achievements concerning renal diseases. With regard to renal nutrition, the paper analyzes the contributions of Beale, Peters and van Slyke, Addis, and Borst, and discusses the advent of the Giordano-Giovannetti diet and its modifications.


Cultural diversity in nursing practice.
This statement describes the features of an operational definition of cultural diversity as it is expressed in nursing practice, education, administration and research. (note: See Definitions which further defines specific terms related to cultural diversity).


Extended contact effects: is exposure to positive outgroup exemplars sufficient or is interaction with ingroup members necessary?
Previous research does not inform us if exposure to positive outgroup exemplars is sufficient to explain the observed prejudice reduction effect of extended contact or if interaction with ingroup members is necessary. An experiment (N = 108) in which Romanian students read identical stories about the friendship between a Roma and a Romanian/Bulgarian found that, while information about close outgroup-outgroup relationships is sufficient to improve outgroup attitudes and reduce intergroup anxiety, information about close ingroup-outgroup relationships has stronger and broader positive effects. Mediational analyses revealed that group emotions rather than intergroup anxiety, ingroup norms, or outgroup norms mediated the effect of extended contact on outgroup perception. A core affect perspective of group emotions is used to explain the results.


Mechanism of inhibition of microtubule polymerization by colchicine: inhibitory potencies of unliganded colchicine and tubulin-colchicine complexes.
The tubulin-colchicine binding reaction appears to involve a number of intermediate steps beginning with rapid formation of a transient preequilibrium complex that is followed by one or more slow steps in which conformational changes in tubulin and colchicine lead to formation of a poorly reversible final-state complex. In the present study, we investigated the relative ability of unliganded colchicine and preformed final-stage tubulin-colchicine complex to incorporate at microtubule ends and to inhibit addition of tubulin at the net assembly ends of bovine brain microtubules in vitro. Addition of 0.1 microM final-stage tubulin-colchicine complex to suspensions of microtubules at polymer-mass steady-state resulted in rapid incorporation of one to two molecules of tubulin-colchicine complex per microtubule net assembly end concomitant with approximately 50-60% inhibition of tubulin addition. Incorporation of colchicine-tubulin complex continued slowly with time, without significant additional change in the rate of tubulin addition. In contrast, addition of unliganded colchicine to microtubule suspensions resulted in incorporation of small numbers of colchicine molecules at microtubule ends and inhibition of tubulin addition only after periods of time that varied from several minutes to approximately 20 min depending upon the concentration of colchicine. Inhibition of tubulin addition beginning with unliganded colchicine increased slowly with time, concomitant with increases in the concentration of final-state tubulin-colchicine complex and the amount of colchicine bound per microtubule end. The results indicate that inhibition of tubulin incorporation at microtubule ends is caused by colchicine-liganded tubulin in the form of a final-state complex.(ABSTRACT TRUNCATED AT 250 WORDS)


Motor profile of patients in minimally responsive and persistent vegetative states.
The purpose of this descriptive clinical study is to document the motor characteristics of patients in minimally responsive and persistent vegetative states. Twelve subjects, presenting a prolonged altered state of consciousness (x = 7.82 years, range 2-27), aged 27-78 years (x = 50, SD = 15.26) were evaluated, using standardized protocols, on the following variables: passive range of motion, observed movements, reflexes, tonus, postural status and reactions. The subjects' level of awareness and responsivity were measured with the Coma/Near Coma (CNC) scale at each of the three data collection sessions. While group CNC scores were stable over the three sessions, fluctuations in the level of awareness of individual subjects was recorded, confirming the heterogeneity of this clientele. Abnormal primitive reflexes were present in all subjects, with the flexor withdrawal (75%), the tonic labyrinthine (36%) and the body-on-body righting reaction (25%) being the most frequently observed. All subjects presented altered tonus, considerable posturing and varied degrees of reduced range of joint motion. A range of abnormal (e.g. chewing, clonus) and normal patterned (e.g. bridging, scratching) movement behaviours was recorded, but these did not translate into functional use, such as rolling. Collectively, the findings stress the complexity of the motor profile of patients in minimally responsive and vegetative states, and suggest the need for physiotherapists to become more actively involved in the evaluation and treatment of this clientele.


Protective effect of fallopian tubal fluid against activated leucocyte-induced sperm DNA fragmentation: preliminary results.
The integrity of the paternal genome is of paramount importance in the initiation and maintenance of a viable pregnancy. Oxygen radicals (ROS) have been identified as one of the main factors responsible for the induction of sperm DNA damage. Spermatozoa are mainly protected against ROS-induced damage by seminal plasma. However, this protective effect disappears once spermatozoa enter the female genital tract. The fallopian tube mucosa may play a protective role against ROS-induced sperm damage. The main objective of this study was to determine whether human tubal explants and tubal fluid exert a protective effect on ROS-induced sperm DNA damage. Spermatozoa were exposed to tubal explants and/or tubal fluid in the presence of phorbol myristate acetate (PMA)-activated polymorphonuclear leucocytes or control medium and sperm DNA fragmentation was measured using the TdT-mediated dUTP-biotin nick end labelling (TUNEL) test. Exposure of human spermatozoa to PMA-activated leucocytes resulted in a 2-fold increase in sperm DNA fragmentation. Co-incubation of spermatozoa with tubal explants did not reduce this damage. However, pre-incubation of spermatozoa with tubal fluid resulted in a statistically significant reduction in sperm DNA fragmentation levels, comparable to those observed in control. In conclusion, tubal fluid appears to protect against activated leucocyte-induced sperm DNA fragmentation, thus preserving the integrity of the paternal genome.


Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection.
This study examined the effects of the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count after pulmonary infection. Sprague‒Dawley rats were subjected to tracheal injection of lipopolysaccharide (LPS) to establish animal models of pulmonary infection. By inhibiting the PI3K/AKT pathway or inhibiting/inducing mitochondrial autophagy in macrophages, the severity of the pulmonary infection and the leukocyte count were altered. The PI3K/AKT inhibition group did not show a significant difference in leukocyte counts compared with the infection model group. Mitochondrial autophagy induction alleviated the pulmonary inflammatory response. The infection model group had significantly higher levels of LC3B, Beclin1, and p-mTOR than the control group. The AKT2 inhibitor group exhibited significantly increased levels of LC3B and Beclin1 compared with the control group (P < 0.05), and the Beclin1 level was significantly higher than that in the infection model group (P < 0.05). Compared with the infection model group, the mitochondrial autophagy inhibitor group exhibited significantly decreased levels of p-AKT2 and p-mTOR, whereas the levels of these proteins were significantly increased in the mitochondrial autophagy inducer group (P < 0.05). PI3K/AKT inhibition promoted mitochondrial autophagy in macrophages. Mitochondrial autophagy induction activated the downstream gene mTOR of the PI3K/AKT pathway, alleviated pulmonary inflammatory reactions, and decreased leukocyte counts.


Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495 and its sole DNA topoisomerase I.
The MazEF systems are thought to contribute to the capacity for long-term dormancy observed in the human pathogen, Mycobacterium tuberculosis. However, except for their functions as mRNA interferases, little is known regarding any additional cellular functions of these systems in the pathogen. In the present study, we observed a negative interplay between MazF protein Rv1495 and the sole M. tuberculosis DNA topoisomerase I (MtbTopA) with respect to protein functions. Through its C-terminal domain, MtbTopA physically interacted with and inhibited the mRNA cleavage activity of Rv1495. Rv1495, in turn, inhibited the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA. An N-terminus fragment of Rv1495, designated Rv1495-N(29-56), lost mRNA cleavage activity, but retained a significant physical interaction and inhibitory effect on TopA proteins from both M. tuberculosis and M. smegmatis. This fragment, although less effective than the full-length protein, was able to inhibit mycobacterial growth when expressed through a recombinant plasmid in M. smegmatis. The Rv1495 physically interacted with the M. smegmatis TopA both in vitro and in vivo. Our findings imply that MazEF systems can affect bacterial survival by a novel mechanism that allows direct modulation of M. tuberculosis topoisomerase I.


Effects of modern eating patterns on the cardiac autonomic nervous system in young Japanese males.
The aim of this study was to determine the effects of the single intake of a high-energy and high-fat meal, of that of a moderate-energy and high-carbohydrate meal, and of fasting, which are major global eating patterns involving the combination of various levels of energy and nutrients, on heart rate variability in healthy young males. Participants were assigned to three groups: the high-energy and high-fat meal group, the moderate-energy and high-carbohydrate meal group, and the fasting group (no meal) in a randomized crossover design. The R-R intervals were continuously recorded before and after meals. Physiological and psychological data were obtained before and 30, 60, 90, and 120 min after meal intake. The main results were: (1) decreased sympathetic modulation of the heart and increased parasympathetic modulation of the heart in the fasting group, indicated by an unchanged heart rate, a decreased lowfrequency/high-frequency ratio, and increased high-frequency power of heart rate variability in the fasting group; (2) cardiac sympathetic activation or parasympathetic withdrawal after the intake of either a high-energy and high-fat meal or a moderate-energy and high-carbohydrate meal, indicated by increases in the heart rate and the low-frequency/high-frequency ratio of heart rate variability, and a decrease in the high-frequency power of heart rate variability in both the high-energy and high-fat meal group and the moderate-energy and high-carbohydrate meal group; and (3) the high-energy and high-fat meal group and the moderate-energy and high-carbohydrate meal group showed similar movement in physiological and psychological measurements after the meal intake. In conclusion, the intake of the high-energy and high-fat meal and the moderate-energy and high-carbohydrate meal similarly activated sympathetic modulation of the heart, whereas fasting suppressed sympathetic modulation of the heart compared with the other two eating groups in healthy young males.


Proceedings from the 3rd International Conference on Microbiome Engineering.
The human microbiome has been inextricably linked to multiple facets of human physiology. From an engineering standpoint, the ability to precisely control the composition and activity of the microbiome holds great promise for furthering our understanding of disease etiology and for new avenues of therapeutic and diagnostic agents. While the field of microbiome research is still in its infancy, growing engineering efforts are emerging to enable new studies in the microbiome and to rapidly translate these findings to microbiome-based interventions. At the 3rd International Conference on Microbiome Engineering, leading experts in the field presented state-of-the-art work in microbiome engineering, discussing probiotics, prebiotics, engineered microbes, microbially derived biomolecules, and bacteriophage.


Cortical Thickness and Cognitive Performance After Out-of-Hospital Cardiac Arrest.
Cognitive impairment is common in long-term survivors of out-of-hospital cardiac arrest (OHCA) but corresponding neuroimaging data are lacking. This study explored the relationship among the cortical brain structure, cognitive performance, and clinical variables after OHCA. Three months after resuscitation, 13 OHCA survivors who had recovered from a coma to living independently and 19 healthy controls were assessed by cerebral magnetic resonance imaging and neuropsychological tests quantifying memory, fine-motor coordination, and attention/executive functions. Cortical thickness (Cth) and surface area (SA) were compared between groups and analyzed for relationships with cognitive performance as well as the clinical variables of coma duration and the time to return of spontaneous circulation (ROSC). All analyses were controlled for age and sex. Analyses of SA revealed no significant differences. Compared with controls, survivors had significantly reduced memory and fine-motor coordination and significantly thinner cortex in large clusters in the frontal, parietal, and inferior temporal cortices, with additional regions in the left occipital lobe and the left temporal lobe. Widespread thinner cortical regions were significantly associated with decreased memory performance in survivors when compared with those in controls and were significantly associated with an increased time to ROSC and increased coma duration in the OHCA group. Increased coma duration, but not increased time to ROSC, was significantly correlated with cognitive test performance. The results suggest that widespread Cth reductions correspond to the cognitive impairments observed after OHCA. Neuroimaging studies of long-term OHCA survivors are warranted to guide the development of diagnostics and treatment options.


Epigenetics of colorectal cancer.
Colorectal cancer (CRC) develops through a multistep process that results from the progressive accumulation of mutations and epigenetic alterations in tumor suppressor genes and oncogenes. Epigenetic modifications, that have a fundamental role in the regulation of gene expression, involve DNA methylation, specific histone modifications and non-coding RNAs (ncRNAs) interventions. Many genes have been until now studied to detect their methylation status during CRC carcinogenesis; and the functions of many of these genes in cancer initiation and progression are being clarified. Less is known about the patterns of histone modification alterations in CRC. Epigenetic deregulation of the ncRNAs or the genes involved in their biogenesis have been described in tumor progression and some examples of dysregulated microRNA were found also in CRC cells. Diet has an important role in the etiology of colon cancer. Folate is involved via 5-methyltetrahydrofolate in the conversion of homocysteine to methionine, which is then used to form the main DNA methylating agent S-adenosylmethionine. However, the role of folate in protecting from or in promoting CRC, depending on conditions, is still debated. The study of epigenetic marks to better characterize CRC and to identify new tools for diagnosis and prognosis as well as for therapeutic interventions is extremely promising.


Cytokine secretion by genetically modified nonimmunogenic murine fibrosarcoma. Tumor inhibition by IL-2 but not tumor necrosis factor.
Recent investigations have demonstrated that the in vivo growth of weakly immunogenic murine tumors can be inhibited by genetic manipulations that enable them to secrete a variety of cytokines. Inasmuch as most human tumors fail to elicit a detectable host immune response we questioned whether the growth of a nonimmunogenic murine tumor could be inhibited by the secretion of cytokines. We have thus inserted the cDNA encoding for human IL-2 or TNF into the nonimmunogenic murine fibrosarcoma MCA 102. Tumor cells secreting IL-2 failed to grow in vivo despite normal in vitro growth. This growth inhibition required an intact immune system as tumors grew progressively in mice sublethally irradiated before tumor injection. Tumor inhibition was abrogated by the in vivo depletion, by specific mAb before tumor injection, of either CD8+ T cells or NK cells, but not CD4+ T cells. IL-2 secretion by tumor afforded a significant survival benefit to the animal, and IL-2-secreting tumor limited the growth of admixed nonsecreting parental tumor. Histologic evidence and FACS analyses revealed a dense lymphocytic infiltration of IL-2-secreting tumors composed of both CD4+ and CD8+ T cells. In contrast, secretion of TNF failed to inhibit the growth of MCA 102, and similar lymphocyte subset depletions, or administration of specific anti-TNF mAb had no effect on the growth of TNF secreting MCA 102. In summary, these investigations demonstrated that the host response to this nonimmunogenic tumor can be markedly enhanced by the genetic manipulation of the tumor cells to secrete IL-2, but not TNF. This strategy has potential application for the development of immunotherapies for nonimmunogenic tumors.


Characterization of the Initial Fouling Layer on the Membrane Surface in a Membrane Bioreactor: Effects of Permeation Drag.
In this study, the properties of the initial fouling layer on the membrane surface of a bioreactor were investigated under different operating modes (with or without permeate flux) to improve the understanding of the effect of permeation drag on the formation of the initial fouling layer. It was found that protein was the major component in the two types of initial fouling layers, and that the permeation drag enhanced the tryptophan protein-like substances. The attraction of the initial foulants to the polyvinylidene fluoride (PVDF) membrane was ascribed to the high zeta potential and electron donor component (γ-) of the membrane. Thermodynamic analyses showed that the permeation drag-induced fouling layer possessed high hydrophobicity and low γ-. Due to permeation drag, a portion of the foulants overcame an energy barrier before they contacted the membrane surface, which itself possessed a higher fouling propensity. A declining trend of the cohesive strength among the foulants was found with the increasing development of both fouling layers.


Coagulation Behavior of Antimony Oxyanions in Water: Influence of pH, Inorganic and Organic Matter on the Physicochemical Characteristics of Iron Precipitates.
The presence of inorganic and organic substances may alter the physicochemical properties of iron (Fe) salt precipitates, thereby stabilizing the antimony (Sb) oxyanions in potable water during the chemical treatment process. Therefore, the present study aimed to examine the surface characteristics, size of Fe flocs and coagulation performance of Sb oxyanions under different aqueous matrices. The results showed that surface properties of Fe flocs significantly varies with pH in both Sb(III, V) suspensions, thereby increasing the mobility of Sb(V) ions in alkaline conditions. The negligible change in surface characteristics of Fe flocs was observed in pure water and Sb(III, V) suspension at pH 7. The key role of Van der Waals forces of attraction as well as hydration force in the aggregation of early formed flocs were found, with greater agglomeration capability at higher more ferric chloride dosage. The higher Sb(V) loading decreased the size of Fe flocs and reversed the surface charge of precipitates, resulting in a significant reduction in Sb(V) removal efficiency. The competitive inhibition effect on Sb(III, V) removal was noticed in the presence of phosphate anions, owing to lowering of ζ-potential values towards more negative trajectory. The presence of hydrophobic organic matter (humic acid) significantly altered the surface characteristics of Fe flocs, thereby affecting the coagulation behavior of Sb in water as compared to the hydrophilic (salicylic acid). Overall, the findings of this research may provide a new insight into the variation in physicochemical characteristics of Fe flocs and Sb removal behavior in the presence of inorganic and organic compounds during the drinking water treatment process.


Genotype 3 diversity and quantification of hepatitis E virus RNA.
Genotype 3 hepatitis E viruses (HEVs) are distributed across the world and are now considered to be an emerging public health concern in industrialized countries. At least 10 genotype 3 subtypes have been identified in humans and animals worldwide. It was recently reported that the sensitivities of HEV RNA assays differ greatly. We have assessed the influence of genotype 3 diversity on the performances of two HEV RNA assays: one targeting the ORF3 gene and the other targeting the ORF2 gene. We tested a panel of 5 HEV-positive reference samples of genotypes 3a, 3b, 3c, 3e, and 3f at 10-fold serial dilutions. The HEV RNA concentrations obtained with both reverse transcription (RT)-PCRs were correlated, but the RT-PCR based on ORF2 underestimated the HEV RNA concentrations. The mean [ORF3 - ORF2] difference was 1.41 log copies/ml. We also tested 34 clinical specimens of genotypes 3c (n = 15), 3e (n = 4), and 3f (n = 15), representing the most prevalent subtypes in Europe. The mean [ORF3 - ORF2] differences were 1.41 log copies/ml for genotype 3c, 0.96 log copies/ml for genotype 3e, and 0.70 log copies/ml for genotype 3f. The bias between the 2 RT-PCR assays was significantly greater for genotype 3c than for genotype 3f (P = 0.007). We therefore recommend the use of an RT-PCR protocol based on ORF3 to quantify HEV RNA of genotype 3 strains.


Genetic Factors Associated With Tardive Dyskinesia: From Pre-clinical Models to Clinical Studies.
Tardive dyskinesia is a severe motor adverse event of antipsychotic medication, characterized by involuntary athetoid movements of the trunk, limbs, and/or orofacial areas. It affects two to ten patients under long-term administration of antipsychotics that do not subside for years even after the drug is stopped. Dopamine, serotonin, cannabinoid receptors, oxidative stress, plasticity factors, signaling cascades, as well as CYP isoenzymes and transporters have been associated with tardive dyskinesia (TD) occurrence in terms of genetic variability and metabolic capacity. Besides the factors related to the drug and the dose and patients' clinical characteristics, a very crucial variable of TD development is individual susceptibility and genetic predisposition. This review summarizes the studies in experimental animal models and clinical studies focusing on the impact of genetic variations on TD occurrence. We identified eight genes emerging from preclinical findings that also reached statistical significance in at least one clinical study. The results of clinical studies are often conflicting and non-conclusive enough to support implementation in clinical practice.


Rapid mortality transition of Pacific Islands in the 19th century.
The depopulation of Pacific islands during the 16th to 19th centuries is a striking example of historical mass mortality due to infectious disease. Pacific Island populations have not been subject to such cataclysmic infectious disease mortality since. Here we explore the processes which could have given rise to this shift in infectious disease mortality patterns. We show, using mathematical models, that the population dynamics exhibited by Pacific Island populations are unlikely to be the result of Darwinian evolution. We propose that extreme mortality during first-contact epidemics is a function of epidemiological isolation, not a lack of previous selection. If, as pathogens become established in populations, extreme mortality is rapidly suppressed by herd immunity, Pacific Island population mortality patterns can be explained with no need to invoke genetic change. We discuss the mechanisms by which this could occur, including (i) a link between the proportion of the population transmitting infectious agents and case-fatality rates, and (ii) the course of infection with pathogens such as measles and smallpox being more severe in adults than in children. Overall, we consider the present-day risk of mass mortality from newly emerging infectious diseases is unlikely to be greater on Pacific islands than in other geographical areas.


The relationships among turnover intentions, professional commitment, and job satisfaction of hospital nurses.
This study investigated the relationships among turnover intentions, professional commitment, and job satisfaction of registered nurses. A structured, self-administered questionnaire, including the Professional Commitment Scale, job satisfaction, turnover intentions, and demographic data, was distributed to 2,550 registered nurses. A total of 2,197 subjects completed the questionnaires with an 86.2 per cent response rate. All of the subjects were women. The mean age was 28.56 years. Seventy-two per cent of respondents had graduated with an associate's degree and 59 per cent were unmarried. There was a positive correlation between job satisfaction and professional commitment, intention to leave the organization, and between intention to leave the profession. The negative correlation was significant between professional commitment and turnover intentions, and between job satisfaction and turnover intentions. The discriminant analysis showed that 38.4 per cent of job satisfaction was correctly classified in predicting intention to leave the organization, and 30.5 per cent in predicting the intention to leave the profession. Thirty per cent of professional commitment was correctly classified in predicting intention to leave the organization, and 39.7 per cent in predicting the intention to leave the profession. The study suggests that there were different moderators that affect different turnover intentions of staff nurses.


Lead toxicity and phosphate deficiency in chlamydomonas.
The addition of lead salts to phosphate-containing Chlamydomonas reinhardtii media caused precipitation of Pb(3)(PO(4))(2), effectively removing phosphate from solution. The effect of Pb(2+) on growth of Chlamydomonas in liquid cultures depended strictly on the ratio of the equivalents of Pb(2+) to phosphate present. When the amount of Pb(2+) approached equivalency with phosphate, cell growth was initially slow as cells adhered to the surface of the precipitated Pb(3)(PO(4))(2). Later, cells grew at a normal rate, spread throughout the solution, and reached the same densities obtained in the absence of Pb(2+). Cells did not survive when the amount of Pb(2+) in the culture exceeded the equivalents of phosphate.Elemental analysis showed that in the presence of equivalent Pb(2+) and phosphate, considerable Pb(2+) remained in solution. The concentration of dissolved Pb(2+) did not vary significantly when the amount of Pb(2+) added to the culture was increased slightly, from an amount which permitted growth to an amount which completely prevented growth. The concentration of phosphate was decreased to an undetectable level when the amount of Pb(2+) approached equivalency with phosphate.In the presence of the chelating agent nitrilotriacetic acid, higher concentrations of Pb(2+) remained in phosphate-containing media. The chelated Pb(2+) did not retard the growth of Chlamydomonas.It appears that Pb(2+) is not toxic to Chlamydomonas, but kills cells by depriving them of phosphate.


Determination of trace lithium in uranium compounds by adsorption on activated alumina using a micro-column method.
A novel method using a micro-column packed with active alumina as solid phase was proposed for separation of trace lithium from uranium compounds prior to determination. The method is based on a preliminary chromatographic separation of the total amount of uranium. This separation involves passing the solution containing sodium carbonate through active alumina and then eluting the trace lithium retained by the solid phase with a solution of sulfuric acid. Two modes, off-line and on-line micro-column preconcentration, were performed. In conjunction with atomic absorption spectrometry, this on-line preconcentration technique allows a determination of lithium at 10(-9) level. Both off-line and on-line mode operation conditions were investigated in separation and determination of trace lithium by micro-column method (length of column bed, flow rate, etc.). The adsorption capacity of activated alumina was found to be 343 microg g(-1) for lithium. Under the optimal operation condition, the detection limit (DL) of on-line preconcentration corresponding to three times the standard deviation of the blank (S/N = 3) was found to be 1.3 ng mL(-1) and the RSD of this method is 3.32% (n = 5). The on-line calibration graph was linear over the range 20 - 200 ng mL(-1). A good preconcentration factor 820 was achieved by experiment under the on-line mode. The developed method was applied to the analysis of trace lithium in nuclear grade uranium compounds.


[Effect of tobramycin with topical diclofenac on arachidonic acid in endotoxin-induced uveitis].
We studied if tobramycin associated to sodium diclofenac modifies the drug effect of the latter on arachidonic acid metabolism in an endotoxin induced uveitis (EIU) model in albino rabbits. Experimental uveitis was induced by intravitreal injection of a 10 ng lipopolysaccharide A Salmonella typhimurium endotoxin dissolved in 5 microl saline solution in the right eye of experimental animals. We have used 48 animals (4 groups of 12 animals each). The control group (G-I) was injected with saline solution (5 microl); the endotoxin group (G-II) was injected with 5 microl of ET; group III and IV were injected with the same amount of ET and treated with topical sodium diclofenac (1%) (Group III) and tobramycin and sodium diclofenac (0.3%) (Group IV) two hours before the administration of endotoxin and then every two hours until 24 hours, when we determined E2 prostaglandin and B4 leukotriene concentration in aqueous humor obtained by paracentesis of the anterior chamber. We observed how the E2 prostaglandin concentration was reduced in the two treatment groups compared with the endotoxin group (p<0.01). However, there were no differences between groups III and IV (p>0.01). There was a mild increase of B4 leukotriene in both treatment groups, which was not significant in relationship to the endotoxin group (p>0.01). No differences were found between the two treatment groups (p>0.01). Using the association of tobramycin does not affect the action of sodium diclofenac in arachidonic acid metabolism in endotoxin induced uveitis.


Mind over body: A neuroergonomic approach to assessing motor performance under stress in older adults.
Stress impairs motor performance, which is exacerbated with age. Stress also impairs brain activity in the prefrontal cortex, which communicates with the motor areas of the brain to regulate exercise and motor performance. To develop ergogenic strategies for the aging workforce, mind (brain)-body mechanisms behind the effect of stress on neuromuscular performance need to be well understood. This study investigated the influence of social stress on motor performance and information flow between the frontal and motor regions of the brain during intermittent handgrip contractions among older adults. Thirty older adults, balanced by gender, performed intermittent handgrip contractions at 30% of maximum strength before and after being subjected to a social stressor. Force steadiness, strength loss, root mean square electromyogram (EMG) activity, activation of the brain regions, and functional and effective connectivity between the frontal and motor brain regions were computed for pre- and post-stressor handgrip contractions. Older men exhibited improved motor performance after the stressor and concomitant reduction in functional connectivity between the frontal-motor brain regions ipsilateral to the contracting hand. Additionally, while both sexes exhibited significant causal information flow, i.e., effective connectivity, from the frontal to the motor regions of the brain, irrespective of the stressor, older women exhibited a bidirectional effective connectivity between the frontal-motor brain regions after the stressor. Stress had a facilitative effect on the motor performance of older men through compensatory brain network reorganization. Older women exhibited comparable motor performance pre/post stress, despite showing an increase in bidirectional information flow between the frontal-motor areas. Employing brain hemodynamics can facilitate better understanding of the impact of stress on neuromuscular performance and its differential impacts on brain network reorganization between the sexes.


Magnetic Resonance Features of Lower-grade Gliomas in Prediction of the Reverse Phase Protein A.
The Cancer Genome Atlas Research Network identified 4 novel protein expression-defined subgroups in patients with lower-grade gliomas (LGGs). The RPPA3 subtype had high levels of Epidermal Growth Factor Receptor and Human epidermal growth factor receptor-2, further increasing the chances for targeted therapy. In this study, we aimed to explore the relationships between magnetic resonance features and reverse phase protein array (RPPA) subtypes (R1-R4). Survival estimates for the Cancer Genome Atlas cohort were generated using the Kaplan-Meier method and time-dependent receiver operating characteristic curves. A total of 153 patients with LGG with brain magnetic resonance imaging from The Cancer Imaging Archive were retrospectively analyzed. Least absolute shrinkage and selection operator algorithm was used to reduce the feature dimensions of the RPPA3 subtype. A total of 51 (33.3%) RPPA1 subtype, 42 (27.4) RPPA2 subtype, 19 (12.4%) RPPA3 subtype, and 38 (24.8%) RPPA4 subtype were identified. On multivariate logistic regression analysis, subventricular zone involvement [odds ratio (OR), 0.370; P = 0.006; 95% confidence interval (CI), 0.181-0.757) was associated with RPPA1 subtype [area under the curve (AUC), 0.598]. Volume of 60 cm3 or greater (OR, 5.174; P < 0.001; 95% CI, 2.182-12.267) was associated with RPPA2 subtype (AUC, 0.684). Proportion contrast-enhanced tumor greater than 5% (OR, 4.722; P = 0.010; 95% CI, 1.456-15.317), extranodular growth (OR, 5.524; P = 0.010; 95% CI, 1.509-20.215), and L/CS ratio equal to or greater than median (OR, 0.132; P = 0.003; 95% CI, 0.035-0.500) were associated with RPPA3 subtype (AUC, 0.825). Proportion contrast-enhanced tumor greater than 5% (OR, 0.206; P = 0.005; 95% CI, 0.068-0.625) was associated with RPPA4 subtype (AUC, 0.638). For the prediction of RPPA3 subtype, the nomogram showed good discrimination, with an AUC of 0.825 (95% CI, 0.711-0.939) and was well calibrated. The RPPA3 subtype was associated with shortest mean overall survival (RPPA3 subtype vs other: 613 vs 873 days; P < 0.05). The time-dependent receiver operating characteristic curves for the RPPA3 subtype was 0.72 (95% CI, 0.60-0.84) for survival at 1 year. Decision curve analysis indicated that prediction for the RPPA3 model was clinically useful. The RPPA3 subtype is an unfavorable prognostic biomarker for overall survival in patients with LGG. Radiogenomics analysis of magnetic resonance features can predict the RPPA subtype preoperatively and may be of clinical value in tailoring the management strategies in patients with LGG.


Binding of lectins to novel migration promoters on cardiac mesenchymal cells in the chick.
Chicken serum promotes migration of cardiac mesenchymal cells of chick embryos in vitro. In the present study, migration promotion of unknown migration promoters in chicken serum was examined by using lectins. Cardiac mesenchymal cells of the conotruncal and atrioventricular cushions were cultured on collagen type-I gel with medium including chicken serum. A concentration (100 micrograms/ml) of Concanavalin A (Con A), peanut agglutinin (PNA), pisum sativum agglutinin (PSA), soybean agglutinin (SBA) or wheat germ agglutinin (WGA) was added to the medium. Con A, PSA, and WGA inhibited migration, while PNA and SBA did not affect migration of cardiac mesenchymal cells. WGA inhibited migration in a concentration dependent manner. Preincubation of WGA with specific binding monosaccharides (alpha-D-N-acetylglucosamine and alpha-D-N-acetylneuraminic acid) clearly reduced the inhibition ability of WGA, while preincubation of Con A and PSA with alpha-D-mannose and alpha-D-glucose did not. On the other hand, Con A-binding proteins, eluted from a Con A affinity column with the buffer including alpha-D-mannose and alpha-D-glucose, promoted migration of cardiac mesenchymal cells, as did WGA-binding proteins. These proteins promoted migration in a concentration dependent manner. Western blotting showed that PSA bound the subunits of collagen type-I, but ConA and WGA did not. In migration inhibition assays by monosaccharides, only N-acetylneuraminic acid inhibited migration of cardiac mesenchymal cells. These results suggested that chicken serum contains novel migration promoters for chick cardiac mesenchymal cells. The promoters are proposed to have the terminal N-acetylglucosamine, N-acetylneuraminic acid, and glucose and/or mannose residues.


Sensitization and crossmatch.
A transfusion effect was observable in the half-lives of recent transplants. The half-life of non-transfused, nulliparous patients transplanted between 1992-1994 was 7.9 years compared to 9.1 years for transfused and 9.6 for retransplanted recipients. Patients whose PRA was measured by AHG were more likely to be broadly sensitized, had a significantly less frequent need for dialysis in the first week posttransplant, and had improved graft outcome regardless of their sensitization level. The decrease in the PNF rate from 10% in 1985 to 3% in 1994 can be attributed to improved crossmatch techniques. Patients with NIH- Flow+ or Wash- AHG+ crossmatches had significantly higher PNF rates. Broadly sensitized recipients (>50% PRA) treated with OKT3 or ALG induction therapy had half the incidence of hospital rejection and a 4-year survival rate of 62% compared to 55% for untreated recipients. Sensitized recipients of zero HLA-A,B,DR- and zero residue-mismatched kidneys had 4-year survival rates of 72% and 65%, respectively, compared with 53% for recipients of residue-mismatched grafts. National sharing has provided HLA-matched kidneys for broadly sensitized recipients. Nineteen percent of broadly sensitized recipients received a zero conventional or HLA residue-mismatched kidney. Regraft recipients matched for HLA residues had the same 4-year graft outcome (68%) as zero HLA-A,B,DR-mismatched recipients, regardless of sensitization level. Both conventional HLA matching and HLA-residue matching reduced the chance that a failed graft would result in broad sensitization. HLA matching was suggested to prevent broad sensitization of pediatric recipients. Half-life for broadly sensitized patients under 18 years of age was 4.9 years and their 4-year graft survival was only 45%.


Nitrate Reduction in Response to CO(2)-Limited Photosynthesis : Relationship to Carbohydrate Supply and Nitrate Reductase Activity in Maize Seedlings.
The effects of CO(2)-limited photosynthesis on (15)NO(3) (-) uptake and reduction by maize (Zea mays, DeKalb XL-45) seedlings were examined in relation to concurrent effects of CO(2) stress on carbohydrate levels and in vitro nitrate reductase activities. During a 10-hour period in CO(2)-depleted air (30 microliters of CO(2)/ per liter), cumulative (15)NO(3) (-) uptake and reduction were restricted 22 and 82%, respectively, relative to control seedlings exposed to ambient air containing 450 microliters of CO(2) per liter. The comparable values for roots of decapitated maize seedlings, the shoots of which had previously been subjected to CO(2) stress, were 30 and 42%. The results demonstrate that reduction of entering nitrate by roots as well as shoots was regulated by concurrent photosynthesis. Although in vitro nitrate reductase activity of both tissues declined by 60% during a 10-hour period of CO(2) stress, the remaining activity was greatly in excess of that required to catalyze the measured rate of (15)NO(3) (-) reduction. Root respiration and soluble carbohydrate levels in root tissue were also decreased by CO(2) stress. Collectively, the results indicate that nitrate uptake and reduction were regulated by the supply of energy and carbon skeletons required to support these processes, rather than by the potential enzymatic capacity to catalyze nitrate reduction, as measured by in vitro nitrate reductase activity.


Effects of Ultraviolet-B Irradiance on Soybean : V. The Dependence of Plant Sensitivity on the Photosynthetic Photon Flux Density during and after Leaf Expansion.
Soybeans (Glycine max [L.] Merr. cv Essex) were grown in a green-house, and the first trifoliate leaf was either allowed to expand under a high photosynthetic photon flux density (PPFD) (1.4 millimoles per square meter per second) or a low PPFD (0.8 millimoles per square meter per second). After full leaf expansion, plants from each treatment were placed into a factorial design experiment with two levels of ultraviolet-B (UV-B) radiation (0 and 80 milliwatts per square meter biologically effective UV-B) and two levels of concomitant PPFD (0.8 and 1.4 millimoles per square meter per second) resulting in a total of eight treatments. Measurements of net photosynthesis and the associated diffusion conductances, ribulose-1,5-bisphosphate carboxylase activity, chlorophyll and flavonoid concentrations, and leaf anatomy were examined for all treatments. Leaves expanded in the high PPFD were unaffected by UV-B radiation while those expanded in the low PPFD were sensitive to UV-B-induced damage. Likewise, plants which were UV-B irradiated concomitantly with the high PPFD were resistant to UV-B damage, while plants irradiated under the low PPFD were sensitive. The results of this study indicate that both anatomical/morphological and physiological/biochemical factors contribute toward plant sensitivity to UV-B radiation.


Regulation of human alveolar macrophage inflammatory cytokine production by interleukin-10.
Alveolar macrophages are the primary source of inflammatory cytokine production in the lung. Both site-specific and differentiation-specific factors play a role in cytokine production, and regulation of this activity in alveolar macrophages is distinctly different from that of circulating blood monocytes. Interleukin-10 (IL-10) inhibits the production of inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)] and enhances production of interleukin-1-receptor antagonist (IL-1ra) from endotoxin-stimulated human monocytes, but the effect of IL-10 on such activity in alveolar macrophages is unknown. This study was undertaken to determine the effect of recombinant IL-10 on endotoxin-stimulated cytokine production by human alveolar macrophages. TNF, IL-1, IL-6, and IL-8 secretions were significantly (P < 0.05) stimulated by endotoxin [lipopolysaccharide (LPS)] and were all significantly (P < 0.05) inhibited (median inhibition = 43%) by IL-10 (10 ng/ml). In contrast, IL-1ra was not stimulated by LPS and basal levels were not affected by IL-10. LPS also did not significantly elevate alveolar macrophage IL-10 secretion (< 100 pg/ml) and basal levels were undetectable (< 15 pg/ml). This potent inhibitory activity of IL-10 on inflammatory cytokine production by human alveolar macrophages suggests that exogenous IL-10 may be useful in treatment of inflammatory lung diseases such as adult respiratory distress syndrome.


1,3,3-Tribenzyl-indolin-2-one.
In the title compound, C(29)H(25)NO, the dihedral angles between the indolin-2-one ring system and the three benzene rings are 62.78 (9), 31.69 (9) and 80.94 (9)°.


Common threads.
Acupuncture and Qigong are aspects of Chinese medicine, an antique medicine of energy which is thousands of years old. Its primary method of diagnosis is the pulse at the wrist, subtle information accessible to physicians only after years of training. Biophotonics presents the same information visually and makes it available to researchers everywhere, setting in place new experimental protocols for acupuncture and energy medicines. Combining this contemporary tool of technology with principles of the ancient medicine will facilitate in the development of not only medical sciences of energy, but all of the sciences of energy that are coming.


New withanolides with TRAIL-sensitizing effect from Physalis pubescens L.
Physalis pubescens L. plant produces nutritious and healthy fruits, called husk tomato or hairy ground cherry. However, its bioactive components are largely unknown. Four new withanolide steroids (1-4) together with one known withanolide (5) were isolated from the extract of P. pubescens L. and their chemical structures were established by extensive spectroscopic analyses. Compounds 1, 3 and 5 showed potent growth inhibitory effects against four human renal cell carcinoma (RCC) cell lines (i.e. 786-O, A-498, Caki-2 and ACHN). Among them, compound 1 was the most potent one with IC50s ranged from 0.30 to 0.77 μM. Further experiment showed that 1 sensitized human RCC cells 786-O to the tumor necrosis factor related apoptosis ligand (TRAIL)-induced apoptosis and increased the expression of C/EBP-homologous protein (CHOP) and death receptor-5 (DR5), leading to activation of the DR5 and caspase-8/3 mediated apoptosis pathway. Molecular docking analysis revealed that compound 1 could bind stably to the TRAIL/DR5 complex through hydrogen bonds. These results suggest that the new withanolide (1) is a lead anti-cancer compound existing in P. pubescens L. and deserves further investigation for RCC prevention and treatment.


Crystalline Silica Promotes Rat Fibrocyte Differentiation in Vitro, and Fibrocytes Participate in Silicosis in Vivo.
The aim of this study was to investigate the effects of SiO2 on fibrocytes and whether fibrocytes participate in silicosis in vivo. A macrophagocyte (AM)/fibrocyte coculture system was established, and AMs were treated with 100 μg/mL SiO2. Flow cytometry was used to detect the number of fibrocytes. Real-time PCR was performed to measure the expression of collagen I, collagen III, and α-SMA mRNA. The levels of collagen I, collagen III, and TGF-β1 protein were determined by ELISA. Immunohistochemical staining was performed to measure α-SMA protein expression. A rat silicosis model was induced by intratracheal instillation of SiO2. Lung histopathological evaluation was conducted using HE and Masson's trichrome staining after 1 and 9 weeks. The number of fibrocytes in peripheral blood or lung tissue of rat was detected by flow cytometry. Double-color immunofluorescence was applied to identify fibrocytes in the lung tissue. Peripheral blood monocytes were found to differentiate into fibrocytes in vitro in a time-dependent manner, and exposure to crystalline silica might potentiate fibrocyte differentiation. In addition, fibrocytes were able to migrate from peripheral blood to the lung tissue, and the number of fibrocytes was increased after SiO2 exposure. Silica exposure potentiates fibrocyte differentiation, and fibrocytes may participate in silicosis in vivo.