A conformation ensemble approach to protein residue-residue contact.
Protein residue-residue contact prediction is important for protein model generation and model evaluation. Here we develop a conformation ensemble approach to improve residue-residue contact prediction. We collect a number of structural models stemming from a variety of methods and implementations. The various models capture slightly different conformations and contain complementary information which can be pooled together to capture recurrent, and therefore more likely, residue-residue contacts. We applied our conformation ensemble approach to free modeling targets from both CASP8 and CASP9. Given a diverse ensemble of models, the method is able to achieve accuracies of. 48 for the top L/5 medium range contacts and. 36 for the top L/5 long range contacts for CASP8 targets (L being the target domain length). When applied to targets from CASP9, the accuracies of the top L/5 medium and long range contact predictions were. 34 and. 30 respectively. When operating on a moderately diverse ensemble of models, the conformation ensemble approach is an effective means to identify medium and long range residue-residue contacts. An immediate benefit of the method is that when tied with a scoring scheme, it can be used to successfully rank models.


Aluminum facilitation of iron-mediated lipid peroxidation is dependent on substrate, pH and aluminum and iron concentrations.
It has been suggested that aluminum (Al) plays a role in neurological disorders. The mechanism of its neurotoxicity has not been established. Brain lipid peroxidation (LP) contributes to neurodegeneration. There have been conflicting reports concerning the Al effect on LP. In the present study, LP of three Folch Fractions from bovine brain and five pure phospholipids was determined in the presence of varying concentrations of iron (Fe) and Al at pH 5.5 and 7.4. Lipid peroxidation was measured as thiobarbituric acid reactive substances. Iron initiated LP, whereas Al did not. However, Al significantly facilitated Fe-mediated LP of bovine brain Folch Fractions I and III, bovine brain-derived phosphatidylserine, and egg yolk phosphatidylcholine. Bovine brain phosphatidylserine was the most susceptible substrate among the lipids tested. Aluminum facilitation of LP was Al and Fe concentration dependent. The peroxidation was greater at pH 5.5 than 7.4. There was no significant Al effect with Folch Fraction V, bovine brain-derived phosphatidylethanolamine, phosphatidylcholine, or sphingomyelin. This study confirmed the ability of Al to facilitate Fe-mediated LP and identified the substrates, pH, and Al concentrations favoring the peroxidation. A potential mechanism for Al facilitation of Fe-mediated LP is proposed.


[Mitochondrial intermembrane space proteins in apoptosis process].
Mitochondria, despite their function in cellular energy metabolism, play an important role in the apoptotic signaling pathways. These organelles in response to the death signal undergo changes resulting in the release of proteins which are essential to conduct apoptosis via mitochondrial pathway. This article is focused on the properties and functions of apoptogenic proteins released from the mitochondrial intermembrane space, i.e., caspases, cytochrome c, Smac/DIABLO, serine protease Omi/HtrA2, AIF and endonuclease G.


Predictive value of F-18 FDG PET/CT quantization parameters for progression-free survival in patients with diffuse large B-cell lymphoma.
To evaluate the predictive significance of F-18 FDG PET/CT quantization parameters for progression-free survival (PFS) in patients with diffuse large B cell lymphoma (DLBCL) before chemotherapy. We conducted a retrospective study involving 60 patients with DLBCL between January 2010 and August 2014 who had undergone F-18 FDG PET/CT scan prior to treatment. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and number of enlarged lymph nodes (>2 cm) were measured. The primary outcome measure was PFS. Spearman rank correlation analysis, univariate and multivariate Cox regression models, receiver operating characteristic (ROC) analysis, and Kaplan-Meir survival curves were used. Spearman analysis determined that the MTV and TLG values were positively related to Ann Arbor stage, National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, and lactate dehydrogenase (LDH) level. The number of enlarged lymph nodes was positively related only to LDH level. The SUVmax value and clinical characteristics were not related. Univariate Cox regression determined that the MTV and TLG values, number of enlarged lymph nodes, and NCCN-IPI score were predictive factors. Multivariate Cox regression determined that the MTV and TLG values and number of enlarged lymph nodes predicted PFS independently of the NCCN-IPI score. The SUVmax value was not predictive of PFS. According to the cut-off determined from ROC analysis, lower MTV and TLG values were highly predictive of favorable PFS. In contrast to SUVmax, the MTV and TLG may be significant prognostic markers for PFS in DLBCL.


Parental socioeconomic position and development of overweight in adolescence: longitudinal study of Danish adolescents.
An inverse social gradient in overweight among adolescents has been shown in developed countries, but few studies have examined whether weight gain and the development of overweight differs among adolescents from different socioeconomic groups in a longitudinal study. The objective was to identify the possible association between parental socioeconomic position, weight change and the risk of developing overweight among adolescents between the ages 15 to 21. Prospective cohort study conducted in Denmark with baseline examination in 1996 and follow-up questionnaire in 2003 with a mean follow-up time of 6.4 years. A sample of 1,656 adolescents participated in both baseline (mean age 14.8) and follow-up (mean age 21.3). Of these, 1,402 had a body mass index (BMI = weight/height2kg/m2) corresponding to a value below 25 at baseline when adjusted for age and gender according to guidelines from International Obesity Taskforce, and were at risk of developing overweight during the study period. The exposure was parental occupational status. The main outcome measures were change in BMI and development of overweight (from BMI < 25 to BMI > = 25). Average BMI increased from 21.3 to 22.7 for girls and from 20.6 to 23.6 in boys during follow-up. An inverse social gradient in overweight was seen for girls at baseline and follow-up and for boys at follow-up. In the full population there was a tendency to an inverse social gradient in the overall increase in BMI for girls, but not for boys. A total of 13.4% developed overweight during the follow-up period. Girls of lower parental socioeconomic position had a higher risk of developing overweight (OR's between 4.72; CI 1.31 to 17.04 and 2.03; CI 1.10-3.74) when compared to girls of high parental socioeconomic position. A tendency for an inverse social gradient in the development of overweight for boys was seen, but it did not meet the significance criteria The levels of overweight and obesity among adolescents are high and continue to rise. Results from this study suggest that the inverse social gradient in overweight becomes steeper for girls and emerges for boys in late adolescence (age span 15 to 21 years). Late adolescence seems to be an important window of opportunity in reducing the social inequality in overweight among Danish adolescents.


BTLA Expression on Th1, Th2 and Th17 Effector T-Cells of Patients with Systemic Lupus Erythematosus Is Associated with Active Disease.
An imbalanced T-cell homeostasis plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Co-stimulatory and co-inhibitory molecules regulate T-cell differentiation, survival, and cytokine production. B- and T-lymphocyte attenuator (BTLA) is a co-inhibitory molecule which negatively regulates T-cell activation. The aim of this study was to investigate BTLA expression on regulatory and effector CD4+ T-cells in SLE patients with and without lupus nephritis (LN) during active and inactive disease. Therefore, peripheral blood of forty-one SLE patients and twenty-one healthy controls (HC) was phenotypically analyzed. Next, ex vivo stimulated T-cells were analyzed for the expression of BTLA on Th1-, Th2-, and Th17-effector cells by flow cytometry. Renal involvement was defined as biopsy-proven LN. Disease activity was assessed by SLE disease activity index (SLEDAI). Percentages of peripheral unstimulated BTLA+ CD4+ T-cells were significantly decreased in SLE patients with active disease. However, ex vivo stimulated Th1, Th2, and Th17 effector T-cells, expressed increased percentages of BTLA expression in active disease. In contrast, the BTLA expression on CD4+CD25++CD127- regulatory T-cells was not significantly different. BTLA seems to be an important co-inhibitory molecule in the T-cell homeostasis of patients with systemic lupus erythematosus and crucial for disease activity.


Should trustees be members of medical staff committees? It's debatable.
Participation of trustees on medical staff committees could provide a positive influence on the tripartite hospital structure. Trustees would be made more aware of the workings of the hospital and of the political, economic, legal, and ethical problems involved in decision making. Physicians, in turn, would be more directly exposed to the views of business and industry concerning health care cost control.


Correlates of Self-Rated Health and Self-Rated Mental Health in Older Chinese Americans.
The present study examined the factors associated with self-rated health (SRH) and self-rated mental health (SRMH) in a sample of 108 older Chinese Americans (MeanAge = 70.6, SD = 7.70). SRH and SRMH were highly associated with each other. In the multiple regression models, chronic conditions and functional disability emerged as significant predictors of poor SRH and SRMH. However, the significance of depressive symptoms was only obtained in the model of SRMH. The findings reflect the body-mind connection among older Chinese Americans and provide implications for integrative health promotion efforts.


Modified RNA-seq method for microbial community and diversity analysis using rRNA in different types of environmental samples.
RNA-seq-based SSU (small subunit) rRNA (ribosomal RNA) analysis has provided a better understanding of potentially active microbial community within environments. However, for RNA-seq library construction, high quantities of purified RNA are typically required. We propose a modified RNA-seq method for SSU rRNA-based microbial community analysis that depends on the direct ligation of a 5' adaptor to RNA before reverse-transcription. The method requires only a low-input quantity of RNA (10-100 ng) and does not require a DNA removal step. The method was initially tested on three mock communities synthesized with enriched SSU rRNA of archaeal, bacterial and fungal isolates at different ratios, and was subsequently used for environmental samples of high or low biomass. For high-biomass salt-marsh sediments, enriched SSU rRNA and total nucleic acid-derived RNA-seq datasets revealed highly consistent community compositions for all of the SSU rRNA sequences, and as much as 46.4%-59.5% of 16S rRNA sequences were suitable for OTU (operational taxonomic unit)-based community and diversity analyses with complete coverage of V1-V2 regions. OTU-based community structures for the two datasets were also highly consistent with those determined by all of the 16S rRNA reads. For low-biomass samples, total nucleic acid-derived RNA-seq datasets were analyzed, and highly active bacterial taxa were also identified by the OTU-based method, notably including members of the previously underestimated genus Nitrospira and phylum Acidobacteria in tap water, members of the phylum Actinobacteria on a shower curtain, and members of the phylum Cyanobacteria on leaf surfaces. More than half of the bacterial 16S rRNA sequences covered the complete region of primer 8F, and non-coverage rates as high as 38.7% were obtained for phylum-unclassified sequences, providing many opportunities to identify novel bacterial taxa. This modified RNA-seq method will provide a better snapshot of diverse microbial communities, most notably by OTU-based analysis, even communities with low-biomass samples.


Reactive and infective dermatoses associated with adult-onset immunodeficiency due to anti-interferon-gamma autoantibody: Sweet's syndrome and beyond.
Immunodeficiency due to anti-interferon-gamma autoantibody (anti-IFN-γ autoAb) is an emerging adult-onset immunodeficiency syndrome predominantly found in Southeast Asians. It is associated with severe or disseminated infections caused by non-tuberculous mycobacteria (NTM) and other opportunistic pathogens. We describe 3 patients with anti-IFN-γ autoAb who developed reactive and infective dermatoses, and thoroughly review the existing literature on dermatoses associated with the immunodeficiency syndrome. Case 1 developed Sweet's syndrome associated with Mycobacterium chelonae lymphadenitis and penicilliosis. Case 2 suffered from multiple episodes of lobular panniculitis during recurrent infections by NTM, Penicillium marneffei and Burkholderia pseudomallei. Both cases responded to immunomodulating agents including corticosteroid and non-steroidal anti-inflammatory drugs. Case 3 had direct skin invasion by M. chelonae and responded to prolonged anti-mycobacterial therapy. A novel working algorithm is proposed for the diagnosis and treatment of these patients who may be encountered by the dermatologist and histopathologist in clinical practice.


Additional Effect of Coronary High-Intensity Plaque on T1-Weighted Magnetic Resonance Imaging With Circulating Malondialdehyde-Modified Low-Density Lipoprotein on Cardiac Events.
Although elevated levels of oxidized low-density lipoprotein (LDL) could play a critical role in vulnerable plaque, there are no studies that have compared coronary high-intensity plaque (HIP) and circulating malondialdehyde-modified (MDA)-LDL levels for the prediction of cardiac events.Methods and Results:A total of 139 patients with coronary artery stenosis (>70%) were examined with non-contrast T1-weighted magnetic resonance imaging (MRI) (HIP: n=64, non-HIP: n=75). Scheduled percutaneous coronary intervention (PCI) for culprit lesions was performed within 48 h after MRI. HIP was defined as a signal intensity of coronary plaque to cardiac muscle ratio (PMR) ≥1.4. We evaluated the subsequent major adverse cardiac events (MACE) during the follow-up period (5.6±1.3 years). MDA-LDL levels were independently associated with the presence of HIP (P<0.0001). The incidence of MACE was 15%, and it was significantly higher in patients with HIP (27%) than in those without HIP (5%; P=0.011). Cox proportional hazard analysis showed MDA-LDL levels (P=0.007) and PMR (P=0.016) were significantly associated with MACE. For MACE prediction, C-statistic values for MDA-LDL, PMR, and PMR+MDA-LDL were 0.724, 0.791, and 0.800, respectively. Compared with MDA-LDL alone, the addition of PMR to MDA-LDL increased net reclassification improvement by 0.78 (P=0.012). MDA-LDL levels might be associated with the presence of HIP in patients with coronary artery disease. Furthermore, adding PMR to MDA-LDL levels markedly improved prediction of subsequent MACE after PCI.


Multidrug toxicity involving sumatriptan.
A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT(1B/1D) receptors and is used for the treatment of migraines. The decedent was a 21-year-old white female found dead in bed by her spouse. No signs of physical trauma were observed and a large number of prescription medications were discovered at the scene. Toxicological analysis of the central blood revealed sumatriptan at a concentration of 1.03 mg/L. Following therapeutic dosing guidelines, sumatriptan concentrations do not exceed 0.095 mg/L. Sumatriptan was isolated by solid-phase extraction and analyzed using liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode. A tissue distribution study was completed with the following concentrations measured: 0.61 mg/L in femoral blood, 0.56 mg/L in iliac blood, 5.01 mg/L in urine, 0.51 mg/kg in liver, 3.66 mg/kg in kidney, 0.09 mg/kg in heart, 0.32 mg/kg in spleen, 0.01 mg/kg in brain, 15.99 mg/kg in lung and 78.54 mg/45 mL in the stomach contents. Carisoprodol, meprobamate, fluoxetine, doxylamine, orphenadrine, dextromethorphan and hydroxyzine were also present in the blood at the following concentrations: 3.35, 2.36, 0.63, 0.19, 0.06, 0.55 and 0.16 mg/L. The medical examiner ruled the cause of death as acute mixed drug toxicity and the manner of death as accident.


Inhibition of trypsin expression in Lutzomyia longipalpis using RNAi enhances the survival of Leishmania.
Leishmania parasites must overcome several barriers to achieve transmission by their sand fly vectors. One of the earliest threats is exposure to enzymes during blood meal digestion. Trypsin-like enzymes appear to be detrimental to parasite survival during the very early phase of development as amastigotes transform into promastigote stages. Here, we investigate whether parasites can affect trypsin secretion by the sand fly midgut epithelium and if inhibition of this process is of survival value to the parasites. Infections of Lutzomyia longipalpis with Leishmania mexicana were studied and these showed that infected sand flies produced less trypsin-like enzyme activity during blood meal digestion when compared to uninfected controls. RNA interference was used to inhibit trypsin 1 gene expression by micro-injection into the thorax, as trypsin 1 is the major blood meal induced trypsin activity in the sand fly midgut. Injection of specific double stranded RNA reduced trypsin 1 expression as assessed by RT-PCR and enzyme assays, and also led to increased numbers of parasites in comparison with mock-injected controls. Injection by itself was observed to have an inhibitory effect on the level of infection, possibly through stimulation of a wound repair or immune response by the sand fly. Leishmania mexicana was shown to be able to modulate trypsin secretion by Lutzomyia longipalpis to its own advantage, and direct inhibition of trypsin gene expression led to increased parasite numbers in the midguts of infected flies. Successful application of RNA interference methodology to Leishmania-infected sand flies now opens up the use of this technique to study a wide range of sand fly genes and their role in the parasite-vector interaction.


Direct 3D Printing of Shear-Thinning Hydrogels into Self-Healing Hydrogels.
Supramolecular hydrogels are used in the 3D printing of high-resolution, multi-material structures. The non-covalent bonds allow the extrusion of the inks into support gels to directly write structures continuously in 3D space. This material system supports the patterning of multiple inks, cells, and void spaces.


The ratio between anionic and cationic trypsin in rat pancreas varies with CCK stimulation.
The effects of long-term hyperstimulation with cholecystokinin (CCK) on the pancreatic contents of anionic and cationic trypsin(ogen) and amylase were studied in the rat. Endogenous hyperCCKemia was evoked in rats by pancreaticobiliary diversion (PBD), and exogenous hyperCCKemia by continuous subcutaneous CCK infusion. In addition, the effect of continuous subcutaneous infusion of the CCK A receptor antagonist devazepide was studied. After 4 weeks blood samples were obtained for the determination of plasma CCK concentrations and the animals were sacrificed. The pancreatic glands were harvested, weighted, and extracted. The extracts were analyzed for anionic and cationic trypsin and amylase. Enzyme contents showed a large interindividual variation. The most consistent change in enzyme pattern was an increase in the ratio between anionic and cationic trypsin in animals with hyperCCKemia (PBD operated or CCK infused). Furthermore, this ratio decreased significantly in animals treated with devazepide. In conclusion, stimulation of the CCK receptor changed the ratio between anionic and cationic trypsin in the pancreatic gland, while it was reversed during blockade of the receptor.


Light-dependent K(+) channels in the mollusc Onchidium simple photoreceptors are opened by cGMP.
Light-dependent K(+) channels underlying a hyperpolarizing response of one extraocular (simple) photoreceptor, Ip-2 cell, in the marine mollusc Onchidium ganglion were examined using cell-attached and inside-out patch-clamp techniques. A previous report (Gotow, T., T. Nishi, and H. Kijima. 1994. Brain Res. 662:268-272) showed that a depolarizing response of the other simple photoreceptor, A-P-1 cell, results from closing of the light-dependent K(+) channels that are activated by cGMP. In the cell-attached patch recordings of Ip-2 cells, external artificial seawater (ASW) was replaced with a modified ASW containing 150 mM K(+) and 200 mM Mg(2+) to suppress any synaptic input and to maintain the membrane potential constant. When Ip-2 cells were equilibrated with this modified ASW, the internal K(+) concentration was estimated to be 260 mM. Light-dependent single-channels in the cell-attached patch on these cells were opened by light but scarcely by voltage. After confirming the light-dependent channel activity in the cell-attached patches, an application of cGMP to the excised inside-out patches newly activated a channel that disappeared on removal of cGMP. Open and closed time distributions of this cGMP-activated channel could be described by the sum of two exponents with time constants tau(o1), tau(o2) and tau(c1), tau(c2), respectively, similar to those of the light-dependent channel. In both the channels, tau(o1) and tau(o2) in ms ranges were similar to each other, although tau(c2) over tens of millisecond ranges was different. tau(o1), tau(o2), and the mean open time tau(o) were both independent of light intensity, cGMP concentration, and voltage. In both channels, the open probability increased as the membrane was depolarized, without changing any of tau(o2) or tau(o). In both, the reversal potentials using 200- and 450-mM K(+)-filled pipettes were close to the K(+) equilibrium potentials, suggesting that both the channels are primarily K(+) selective. Both the mean values of the channel conductance were estimated to be the same at 62 and 91 pS in 200- and 450-mM K(+) pipettes at nearly 0 mV, respectively. Combining these findings with those in the above former report, it is concluded that cGMP is a second messenger which opens the light-dependent K(+) channel of Ip-2 to cause hyperpolarization, and that the channel is the same as that of A-P-1 closed by light.


Transcranial magnetic stimulation intensities in cognitive paradigms.
Transcranial magnetic stimulation (TMS) has become an important experimental tool for exploring the brain's functional anatomy. As TMS interferes with neural activity, the hypothetical function of the stimulated area can thus be tested. One unresolved methodological issue in TMS experiments is the question of how to adequately calibrate stimulation intensities. The motor threshold (MT) is often taken as a reference for individually adapted stimulation intensities in TMS experiments, even if they do not involve the motor system. The aim of the present study was to evaluate whether it is reasonable to adjust stimulation intensities in each subject to the individual MT if prefrontal regions are stimulated prior to the performance of a cognitive paradigm. Repetitive TMS (rTMS) was applied prior to a working memory task, either at the 'fixed' intensity of 40% maximum stimulator output (MSO), or individually adapted at 90% of the subject's MT. Stimulation was applied to a target region in the left posterior middle frontal gyrus (pMFG), as indicated by a functional magnetic resonance imaging (fMRI) localizer acquired beforehand, or to a control site (vertex). Results show that MT predicted the effect size after stimulating subjects with the fixed intensity (i.e., subjects with a low MT showed a greater behavioral effect). Nevertheless, the individual adaptation of intensities did not lead to stable effects. Therefore, we suggest assessing MT and account for it as a measure for general cortical TMS susceptibility, even if TMS is applied outside the motor domain.


Influenza and risk of later celiac disease: a cohort study of 2.6 million people.
Influenza has been linked to autoimmune conditions, but its relationship to subsequent celiac disease (CD) is unknown. Our primary aim was to determine the risk of CD after influenza. A secondary analysis examined the risk of CD following pandemic influenza vaccination. This nationwide register-based cohort study included 2,637,746 Norwegians (born between 1967-2013) followed during 2006-2014 with information on influenza diagnosed in primary or non-primary care, pandemic vaccination (Pandemrix), and subsequent CD. Cox regression yielded hazard ratios adjusted (HR) for socio-demographic characteristics and earlier healthcare use. During 13,011,323 person-years of follow-up 7321 individuals were diagnosed with CD (56/100,000 person-years). There were 351,666 individuals diagnosed with influenza, including 82,980 during the 2009-2010 pandemic, and 969,968 individuals were vaccinated. Compared with participants without influenza, who had a CD incidence of 55/100,000 person-years, those diagnosed with seasonal and pandemic influenza had a rate of 68 and 78, per 100,000 person-years, respectively. The HR for CD was 1.29 (95%CI, 1.21-1.38) after seasonal influenza and 1.29 (95%CI, 1.15-1.44) after pandemic influenza; HRs remained significantly increased one year after exposure, when restricted to laboratory-confirmed influenza, and after multivariate adjustments. The reverse association, i.e., risk of influenza after CD, was not significant (HR 1.05; 95%CI, 0.98-1.12). The HR for CD after pandemic vaccination was 1.08 (95%CI, 1.03-1.14). A positive association with influenza diagnosis is consistent with the hypothesis that infections may play a role in CD development. We could neither confirm a causal association with pandemic vaccination, nor refute entirely a small excess risk.


Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration.
We investigated proinflammatory M1 and immunomodulatory M2 activation profiles of circulating monocytes in relapsing experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, and tested whether altered M1/M2 equilibrium promotes CNS inflammation. Approaches of MRI macrophage tracking with USPIO nanoparticles and expression patterns of M1/M2 macrophages and microglia in brain and M1/M2 monocytes in blood samples at various disease stages revealed that M1/M2 equilibrium in blood and CNS favors mild EAE, while imbalance towards M1 promotes relapsing EAE. We consequently investigated whether M2 activated monocyte restoration in peripheral blood could cure acute clinical EAE disease. Administration of ex vivo activated M2 monocytes both suppressed ongoing severe EAE and increased immunomodulatory expression pattern in lesions, confirming their role in the induction of recovery. We conclude that imbalance of monocyte activation profiles and impaired M2 expression, are key factors in development of relapses. Our study opens new perspectives for therapeutic applications in MS.


A minimally invasive surgical approach for periodontal regeneration: surgical technique and observations.
Increasingly, patients referred to periodontists have undergone some form of non-surgical periodontal treatment prior to their referral. As a result of this, there is an increased need to treat isolated, rather than generalized, periodontal defects. A surgical technique that utilizes small incisions and a limited access approach for treating isolated periodontal defects is described. Results from the use of the minimally invasive surgical (MIS) technique for periodontal regeneration in a comparison study appear to be similar to those where a more traditional surgical approach has been used. Some of the apparent advantages and disadvantages of using the MIS approach are discussed.


Schedules of Controlled Substances: Placement of AH-7921 Into Schedule I. Final order.
With the issuance of this final order, the Administrator of the Drug Enforcement Administration places the substance AH-7921 (Systematic IUPAC Name: 3,4-dichloro-N-[(1dimethylamino)cyclohexylmethyl]benzamide), including its isomers, esters, ethers, salts, and salts of isomers, esters and ethers, into schedule I of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act and is required in order for the United States to discharge its obligations under the Single Convention on Narcotic Drugs, 1961. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, import, export, engage in research or conduct instructional activities with, or possess), or propose to handle, AH-7921.


Enzyme stabilization by covalent binding in nanoporous sol-gel glass for nonaqueous biocatalysis.
A unique nanoporous sol-gel glass possessing a highly ordered porous structure (with a pore size of 153 A in diameter) was examined for use as a support material for enzyme immobilization. A model enzyme, alpha-chymotrypsin, was efficiently bound onto the glass via a bifunctional ligand, trimethoxysilylpropanal, with an active enzyme loading of 0.54 wt%. The glass-bound chymotrypsin exhibited greatly enhanced stability both in aqueous solution and organic solvents. The half-life of the glass-bound alpha-chymotrypsin was >1000-fold higher than that of the native enzyme, as measured either in aqueous buffer or anhydrous methanol. The enhanced stability in methanol, which excludes the possibility of enzyme autolysis, particularly reflected that the covalent binding provides effective protection against enzyme inactivation caused by structural denaturation. In addition, the activity of the immobilized alpha-chymotrypsin was also much higher than that of the native enzyme in various organic solvents. From these results, it appears that the glass-enzyme complex developed in the present work can be used as a high-performance biocatalyst for various chemical processing applications, particularly in organic media. Published by John Wiley & Sons


Gamma-glutamyltranspeptidase-mediated degradation of diclofenac-S-acyl-glutathione in vitro and in vivo in rat.
Diclofenac, a nonsteroidal antiinflammatory drug, is known to be metabolized to chemically reactive intermediates that transacylate GSH forming diclofenac-S-acyl-glutathione (D-SG) in vivo in rat and in vitro in rat and human hepatocytes. Recently, it was reported that the treatment of rats with diclofenac led to a substantial decrease in the activity of hepatic gamma-glutamyltranspeptidase (gamma-GT), an extracellular canalicular membrane enzyme. Because studies have indicated that D-SG is a chemically reactive transacylating species that is excreted into rat bile, we propose that D-SG formed in the liver may be a substrate for, and potential inhibitor of, hepatic gamma-GT. The present experiments were performed to investigate the ability of D-SG to be a substrate for gamma-GT in vivo in rat and in vitro with commercially available gamma-GT enzyme. We also examined the ability of D-SG to inhibit gamma-GT in vitro. Thus, LC-MS/MS analysis of bile extracts from diclofenac-dosed rats (200 mg/kg, iv) showed the presence of the gamma-GT-mediated D-SG degradation product diclofenac-N-acyl-cysteinylglycine (D- N-CG), where a total of approximately 8 microg was excreted 6 h postadministration. When D-SG (100 microM) was incubated with gamma-GT (1 unit/mL), the GSH adduct was degraded in a linear time-dependent fashion where approximately 94 microM D- N-CG was formed after 20 min of incubation. Dialysis studies showed that inhibition of gamma-GT by D-SG was completely reversible. Further inhibition studies showed that D-SG is a competitive inhibitor of the gamma-GT enzyme. Results from theses studies indicate that D-SG is a substrate for gamma-GT; however, the conjugate may not contribute significantly to the decrease in gamma-GT activity reported to occur in vivo in rat.


Histamine and selenium in lung cancer.
The relationship between allergies and cancer incidence and the role played by histamine on the immune system and on inhibiting tumor growth have been the subject of study in our group. The influence of histamine dosage on free radicals was investigated in both lung cancer and healthy subjects. Plasmatic selenium levels in the same patients were assayed in order to highlight the role played by free radicals in lung cancer. The role of selenium on the genesis of lung cancer is well known. Thirty-seven male patients with lung adenocarcinoma or squamous carcinoma were tested. The control group included thirty-nine healthy male subjects. The results indicated a significant decrease in histamine plasma levels in subjects with cancer (p=0.0038) compared to the healthy subjects. Smoking significantly reduced the histamine plasma levels in cancer patients (p=0.0044). Such a decrease was not significant in the controls (p=0.063). A significant decrease in selenium plasma levels in the cancer patients (p=0.005) was also observed. The data suggest that histamine and selenium are two factors involved in the pathogenesis of lung cancer, which could be used in protective and therapeutic strategies.


Sihler's whole mount nerve staining technique: a review.
Sihler's stain is a whole mount nerve staining technique that renders other soft tissue translucent or transparent while staining the nerves. It permits mapping of entire nerve supply patterns of organs, skeletal muscles, mucosa, skin, and other structures after the specimens are fixed in neutralized formalin, macerated in potassium hydroxide, decalcified in acetic acid, stained in Ehrlich's hematoxylin, destained in acetic acid, and cleared in glycerin. The unique advantage of Sihler's stain over other anatomical methods is that all the nerves within the stained specimen can be visualized in their three-dimensional positions. To date, Sihler's stain is the best tool for demonstrating the precise intramuscular branching and distribution patterns of skeletal muscles, which are important not only for anatomists, but also for physiologists and clinicians. Advanced knowledge of the neural structures within mammalian skeletal muscles is critical for understanding muscle functions, performing electrophysiological experiments and developing novel neurosurgical techniques. In this review, Sihler's stain is described in detail and its use in nerve mapping is surveyed. Special emphasis is placed on staining procedures and troubleshooting, strengths and limitations, applications, major contributions to neuroscience, physiological and clinical significance, and areas for further technical improvement that deserve future research.


Assessment of uncertainty in long-term mass balances for acidification assessments: a MAGIC model exercise.
Long-term (1860-2010) catchment mass balance calculations rely on models and assumptions which are sources of uncertainty in acidification assessments. In this article, we report on an application of MAGIC to model acidification at the four Swedish IM forested catchments that have been subject to differing degrees of acidification stress. Uncertainties in the modeled mass balances were mainly associated with the deposition scenario and assumptions about sulfate adsorption and soil mass. Estimated base cation (BC) release rates (weathering) varied in a relatively narrow range of 47-62 or 42-47 meq m(-2) year(-1), depending on assumptions made about soil cation exchange capacity and base saturation. By varying aluminum solubility or introducing a dynamic weathering feedback that allowed BC release to increase at more acidic pHs, a systematic effect on predicted changes in acid neutralizing capacity (ΔANC ca. 10-41 μeq l(-1)) and pH (ca. ΔpH = 0.1-0.6) at all sites was observed. More robust projections of future changes in pH and ANC are dependent on reducing uncertainties in BC release rates, the timing, and extent of natural acidification through BC uptake by plants, temporal changes in soil element pools, and fluxes of Al between compartments.


Airway misadventures in adult critical care: a concise narrative review of managing lost or compromised artificial airways.
Loss or compromise of artificial airways in critically ill adults can lead to serious adverse events, including death. In contrast to primary emergency airway management, the optimal management of such scenarios may not be well defined or appreciated. Endotracheal tube cuff leaks may compromise both oxygenation and ventilation, and supraglottic cuff position must first be recognized and distinguished from other reasons for gas leakage during positive pressure ventilation. Although definitive management involves tube exchange, if direct visualization is possible temporizing measures can often be considered. Unplanned extubation confers variable and context-specific risks depending on patient anatomy and physiological status. Because risk factors for unplanned extubation are well established, bundled interventions can be employed for mitigation. Tracheostomy tube dislodgement accounts for a substantial proportion of death and disability related to airway management in critical care settings. Consensus guidelines and algorithmic management of such scenarios are key elements of risk mitigation. Management of lost or otherwise compromised artificial airways is a key skill set for adult critical care clinicians alongside primary emergency airway management.


The - 564 A/G polymorphism in the promoter region of the proteinase 3 gene associated with Wegener's granulomatosis does not increase the promoter activity.
Proteinase 3 is the major autoantigen in patients with Wegener's granulomatosis. Earlier studies have shown that circulating leucocytes from patients with Wegener's granulomatosis show elevated proteinase 3 surface expression and mRNA levels. Wegener's granulomatosis patients also have increased levels of proteinase 3 in plasma. A single nucleotide polymorphism (SNP) (-564 A/G SNP) in the promoter region has been associated with disease. This SNP introduces a new potential Sp1 transcription factor binding site that may be responsible for the observed up-regulated expression of proteinase 3. To investigate this a 740 base pair long region of the promoter was cloned from genomic DNA. The disease-associated -564 A/G, as well as a control -621 A/G exchange, were introduced by polymerase chain reaction mutagenesis and cloned into a luciferase reporter vector. Endogenous expression levels of proteinase 3 mRNA and promoter activity of the cloned constructs were measured in three myeloid cell lines, HL-60, U937 and NB-4, and in epithelial HeLa cells. The results demonstrate a good correlation between the endogenous proteinase 3 mRNA expression and the promoter activity, as judged by luciferase activity. However, no significant differences in activity between the wild-type, polymorphic and the mutated control variant were found. In conclusion, the -564 A/G polymorphism is not responsible for the increased expression levels seen in myeloid cells from patients with Wegener's granulomatosis.


Waste to treasure: Superwetting foam enhanced by bamboo powder for sustainable on-demand oil-water separation.
Low-cost and sustainable superwetting materials are urgently required for oily wastewater treatment. Many poly(vinylidene fluoride) (PVDF)-based materials have been designed for oil-water separation. However, their fabrication processes frequently require toxic organic solvents and high-cost materials (e.g., carbon tubes and graphene). In this study, a highly porous and superhydrophobic bamboo powders (BP)-enhanced PVDF foam (SBPF) was fabricated via an organic solvent-free process. The SBPF exhibits efficient adsorption and recovery for various oils and organic solvents. Moreover, the SBPF shows high adsorption and separation performance under ultraviolet exposure and turbulent environments. It can also be used for water-in-oil emulsions separation, with a high separation efficiency more than 99.3 % under gravity. Interestingly, the amphiphilic PVDF-BP foam (ABPF) shows underwater superoleophobicity and underoil superhydrophobicity after delignification of SBPF. Owing to the conversion of wettability, it presents a high performance in treatment of both surfactant-stabilied water-in-oil and oil-in-water emulsions with the high separation efficiency achieving more than 99.6 % and 99.5 % respectively under gravity. In addition, the ABPF shows a high separation performance even after ten cycles. Hence, this fabricated organic solvent-free foams are promising candidates for sustainable on-demand separation of oils or organic solvents and water in complex environments.


Early postoperative treatment of surgical scars using a fractional carbon dioxide laser: a split-scar, evaluator-blinded study.
Although focus has recently been directed toward the early treatment of surgical scars, the optimal time at which to initiate treatment with fractional laser and its effect on scar remodeling remains controversial. To assess the safety and efficacy of treating surgical scars using an ablative carbon dioxide (CO2 ) fractional laser during the early postoperative period. We performed a prospective, split-scar, evaluator-blinded study on 16 postoperative scars of 15 patients. Patients began treatment 3 weeks after surgery and were treated in two sessions of CO2 fractional laser therapy on half of the scar at 2-week intervals. All patients were followed for 3 months after the final treatment session. Three months after the last treatment, a greater decrease in Vancouver Scar Scale score was noted in the treated half of the scars, especially in terms of texture and thickness. Patients also expressed a significantly greater degree of satisfaction with the treated side as assessed using a subjective 4-point scale. Only one patient experienced any adverse effect, which was the development of hypertrophy, on the treated and untreated side of the scar. CO2 fractional laser is an effective treatment modality for surgical scars in the early postoperative period.


Anterior paraclinoid aneurysms.
The characteristics of a previously unclassified paraclinoid aneurysm arising from the anterolateral (dorsal) wall of the proximal internal carotid artery were retrospectively analyzed in seven patients (five women and two men) who were treated surgically for an aneurysm in this unusual location. One patient presented with subarachnoid hemorrhage (SAH) caused by rupture of this aneurysm. The lesions were found incidentally (five cases) or during investigation of SAH due to another aneurysm (one case). There was a female predominance in this series; all female patients harbored multiple aneurysms. All patients underwent surgery. Removal of the anterior clinoid process was necessary because the proximal neck of the aneurysm was closely adjacent to the dural ring. This special group of aneurysms is very rare, is located exclusively in the intradural space, and carries the risk of SAH. The results of surgical treatment for this aneurysm are quite satisfactory.


Induction of human thioredoxin in cultured human retinal pigment epithelial cells through cyclic AMP-dependent pathway; involvement in the cytoprotective activity of prostaglandin E1.
Human thioredoxin is one of the oxidative stress-inducible proteins and has a protective function against oxidant-induced injury. To evaluate the possible involvement of thioredoxin in the cytoprotective function of prostaglandin E1, we analysed the effect of prostaglandin E1 on cellular injury by hydrogen peroxide and intracellular thioredoxin induction. Cellular survival of human retinal pigment epithelial cell line, established from normal retinal pigment epithelial cells, following exposure to hydrogen peroxide was markedly improved by pretreatment of 1 microm prostaglandin E1. Thioredoxin expression was augmented in a dose-dependent manner when retinal pigment epithelial cells were pretreated with 10 nm-1 microm prostaglandin E1 1 hr before the exposure to hydrogen peroxide. Intracellular cyclic AMP level was elevated by Prostaglandin E1 when the cells were simultaneously exposed to hydrogen peroxide. Forskolin, an activator of adenylate cyclase, and dibutylyl cAMP, a cyclic AMP analog, could also induce thioredoxin and extend survival of retinal pigment epithelial cells. On the other hand, thioredoxin induction and cellular protection by prostaglandin E1 was blocked by Rp diastereoisomer of cyclic adenosine 3', 5', monophosphorothioate, a competitive inhibitor of cyclic AMP dependent protein kinase. Thioredoxin induction was augmented significantly by pretreatment with prostaglandin I2, a stimulator of cyclic AMP dependent signal pathway, while treatment with prostaglandin F2alpha, a stimulator of inositol phosphate-dependent signal pathway, failed to enhance thioredoxin. These findings indicate that prostaglandin E1 has a cytoprotective activity against oxidative injury, partly through thioredoxin induction via cyclic AMP dependent pathway.


Multicentric Adenocarcinomas in a Long-Segment of Barrett's Esophagus.
This report describes a complicated course of a 58-year-old patient with multicentric Barrett's carcinoma within a long-segment of Barrett metaplasia. After abdominal-thoracic resection of the cancer, with incomplete removal of the long-segment metaplastic lesion, invasive carcinoma was diagnosed in the remnant Barrett's segment. Endoscopic mucosal resection was done, but Barrett's mucosa was left in situ again. Recurrent tumor growth was diagnosed only few months later. Finally, transthoracic complete resection on the remnant Barrett's segment was performed. Thus, our case demonstrates impressively the appearance of multicentric adenocarcinomas in Barrett's esophagus and underlines the necessity of resection of the complete Barrett mucosa.


[Visceral leishmaniasis associated with Hodgkin's disease: diagnostic difficulties].
A case of Hodgkin's disease associated from the start with visceral leishmaniasis in the absence of antitumoral treatment shows that leishmaniasis is a severe opportunistic infection in endemic areas and can be masked by the tumoral syndrome of an underlying pathology. Conversely, patients with visceral leishmaniasis must be investigated for a cause of immunosuppression with, in particular, biopsy of accessible lymph nodes. The exceptionally favourable course of this particular case deserved to be high-lighted.


A High-Performance and Low-Cost Soy Flour Adhesive with a Hydroxymethyl Melamine Prepolymer.
To improve the performance of a soy flour (SF)-based adhesive, a low-cost hydroxymethyl melamine prepolymer (HMP) was synthesized and then used to modify the SF-based adhesive. The HMP was characterized, and the performance of the adhesive was evaluated, including its residual rate, functions, thermal stability, and fracture section. Plywood was fabricated to measure wet shear strength. The results indicated that the HMP preferentially reacted with polysaccharose in SF and formed a cross-linking network to improve the water resistance of the adhesive. This polysaccharose-based network also combined with the HMP self-polycondensation network and soy protein to form an interpenetrating network, which further improved the water resistance of the adhesive. With the addition of 9% HMP, the wet shear strength (63 °C) of the plywood was 1.21 MPa, which was 9.3 times that of the SF adhesive. With the HMP additive increased to 15%, the shear strength (100 °C) of the plywood was 0.79 MPa, which met the plywood requirement for exterior use (≥0.7 MPa) in accordance with Chinese National Standard (GB/T 9846.3-2004). With the addition of 9% and 15% HMP, the residual rates of the adhesive improved by 5.1% and 8.5%, respectively. The dense interpenetrating network structure improved the thermal stability of the resultant adhesive and created a compact fracture to prevent moisture intrusion, which further increased the water resistance of the adhesive.


Preparation and optimization of triptolide-loaded solid lipid nanoparticles for oral delivery with reduced gastric irritation.
Triptolide (TP) often causes adverse reactions in the gastrointestinal tract when it is administered orally. This study aimed to prepare and optimize triptolide-loaded solid lipid nanoparticles (TP-SLN) with reduced gastric irritation. The microemulsion technique was used to formulate TP-SLN employing a five-level central composite design (CCD) that was developed for exploring the optimum levels of three independent variables on particle size, encapsulation efficiency (EE) and drug loading (DL). Quadratic polynomial models were generated to predict and evaluate the three independent variables with respect to the three responses. The optimized TP-SLN was predicted to comprise fraction of lipid of 49.73%, surfactant to co-surfactant ratio of 3.25, and lipid to drug ratio of 55.27, which showed particle size of 179.8 ± 5.7 nm, EE of 56.5 ± 0.18% and DL of 1.02 ± 0.003% that were in good agreement with predicted values. In addition, the optimized nanoparticles manifested a sustained-release pattern in vitro and were stable during 3 h of incubation in simulated gastric fluids without significant size change and the majority (91%) of the drug was protected. Furthermore, the nanoparticles did not show obvious gastric irritation caused by oral administration of TP in rats.


Osteomyelitis of the patella: ensure a high index of suspicion and beware the negative aspirate.
We report the case of a 33-year-old man who presented several times to healthcare professionals over a 6-week period with a painful swollen right knee. He had a history of chronic osteomyelitis of the left femur and had recently stopped taking suppressive antibiotics. A joint aspirate did not demonstrate any organisms. On subsequent review by the orthopaedic team MRI was performed which revealed an isolated area of osteomyelitis and an abscess in his right patella. He underwent arthrotomy, debridement and irrigation of the joint alongside antibiotic treatment. We highlight this case, as isolated osteomyelitis of the patella is a rare condition, especially in adults. In addition, the presenting features of osteomyelitis of the patella are varied and joint fluid aspirates often do not reveal an organism. This case therefore aims to raise an awareness of this condition and thereby ensure a high index of suspicion when symptoms or signs are present and inform clinicians of the investigative steps in order to avoid a delay in diagnosis as seen in this case.


Immediate implants placed in infected and noninfected sites after atraumatic tooth extraction and placement with ultrasonic bone surgery.
Only a few reports deal with implants placed in infected postextraction sites. Survival rates of a cohort of immediate implants cases placed in acute and chronically infected sites were compared with a cohort of noninfected ones while (1) tooth extraction and osteotomy sites were prepared with a piezosurgery device and (2) ultrasonication was applied to abate the bacterial charge at infected sites. Eighty-six patients received 168 immediate implants distributed into three groups: noninfected (85), acute (36), and chronically (47) infected sites. Atraumatic extraction and implant osteotomy were performed with an ultrasonic surgery device without flap elevation. All sites received the same medication and surgical protocol; infected sites were ultrasonicated during 30 seconds at 72 W. Kaplan-Meyer survival rates were calculated at 1 year. The 1-year survival rates of the noninfected, chronically, and acute infected groups were 98.8, 100, and 94.4%, respectively. The differences were not statistically significant. No implant was lost after loading. All teeth and roots could be extracted in one piece. Drilling at extraction sockets was uncomplicated, without skidding. Implant survival rates might be similar in infected and noninfected sites when infected sites receive standard medical and surgical treatment and are ultrasonicated. Atraumatic tooth/root extraction and implant placement can be reliably performed with piezoelectric surgery.


Oxidative stress induced cellular signaling in RPE cells.
Oxidative stress is an important factor in the etiology of age-related macular degeneration. In the retinal pigment epithelium, oxidative stress induces protective pathways, notably the phosphatidylinositide 3-kinase (PI3K)/Akt and the nuclear factor erythroid-2 related factor 2 (Nrf2) pathways, but also vascular endothelial growth factor (VEGF) and neuroprotectin D1 (NPD-1) signaling conduct cell protection. Strong oxidative insults result in cell death, mainly mediated via a mitochondrial apoptotic pathway, including cytochrome c release and caspase activation. The role of mitogen activated protein kinases (MAPK) in oxidative stress signaling is diverse and conflicting, conducting protective as well as apoptotic pathways, in addition to involvement in a variety of other cell responses, such as VEGF or matrix metalloproteinases (MMP) upregulation. In addition to signaling deciding cell fate, first insights in inflammatory and extracellular matrix-altering signaling are emerging.


Selective and efficient neural coding of communication signals depends on early acoustic and social environment.
Previous research has shown that postnatal exposure to simple, synthetic sounds can affect the sound representation in the auditory cortex as reflected by changes in the tonotopic map or other relatively simple tuning properties, such as AM tuning. However, their functional implications for neural processing in the generation of ethologically-based perception remain unexplored. Here we examined the effects of noise-rearing and social isolation on the neural processing of communication sounds such as species-specific song, in the primary auditory cortex analog of adult zebra finches. Our electrophysiological recordings reveal that neural tuning to simple frequency-based synthetic sounds is initially established in all the laminae independent of patterned acoustic experience; however, we provide the first evidence that early exposure to patterned sound statistics, such as those found in native sounds, is required for the subsequent emergence of neural selectivity for complex vocalizations and for shaping neural spiking precision in superficial and deep cortical laminae, and for creating efficient neural representations of song and a less redundant ensemble code in all the laminae. Our study also provides the first causal evidence for 'sparse coding', such that when the statistics of the stimuli were changed during rearing, as in noise-rearing, that the sparse or optimal representation for species-specific vocalizations disappeared. Taken together, these results imply that a layer-specific differential development of the auditory cortex requires patterned acoustic input, and a specialized and robust sensory representation of complex communication sounds in the auditory cortex requires a rich acoustic and social environment.


Mechanical Characterization of Liposomes and Extracellular Vesicles, a Protocol.
Both natural as well as artificial vesicles are of tremendous interest in biology and nanomedicine. Small vesicles (<200 nm) perform essential functions in cell biology and artificial vesicles (liposomes) are used as drug delivery vehicles. Atomic Force Microscopy (AFM) is a powerful technique to study the structural properties of these vesicles. AFM is a well-established technique for imaging at nanometer resolution and for mechanical measurements under physiological conditions. Here, we describe the procedure of AFM imaging and force spectroscopy on small vesicles. We discuss how to image vesicles with minimal structural disturbance, and how to analyze the data for accurate size and shape measurements. In addition, we describe the procedure for performing nanoindentations on vesicles and the subsequent data analysis including mechanical models used for data interpretation.


Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication.
This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi). Liver samples, submandibular salivary gland, mesenteric lymph node and tonsils were removed for virological and pathological evaluation. Immunofluorescence analyses on liver and salivary gland sections using confocal laser scanning microscopy revealed the presence of HAV antigen (HAV Ag). The presence of HAV genome was monitored by real-time PCR. The HAV RNA was detected at 7 days postinoculation (dpi), concomitantly in serum, saliva and faeces. The highest HAV viral load was observed in faeces at 15 dpi (10(5) copies/ml), followed by serum viral load of 10(4) copies/ml at 20 dpi and saliva viral load of 10(3 )copies/ml at 7 dpi. The animals showed first histological and biochemical signs of hepatitis at 15 dpi. The HAV antigen (Ag) was present from day 7 until day 60 pi in the liver and salivary glands. The HAV replicative intermediate was also detected in the liver (4.5 x 10(4) copies/mg), salivary glands (1.9 x 10(3) copies/mg), tonsils (4.2 x 10(1) copies/mg) and lymph nodes (3.4 x 10(1) copies/mg). Our data demonstrated that the salivary gland as an extrahepatic site of early HAV replication could create a potential risk of saliva transmitted infection. In addition, the cynomolgus monkey was confirmed as a suitable model to study the pathogenesis of HAV human infection.


NCI series of cell lines: an historical perspective.
The NCI series of cell lines represent a unique collection of permanent human tumor cell lines established by one laboratory over a period of approximately 16 years. More than 300 cell lines were established, mainly from human lung cancers (both small cell and non-small cell types). In addition, smaller numbers of lines were established from rare and unusual tumors such as cutaneous T cell lymphomas, myelomas and adrenal cortical carcinoma. The T cell lines played a pivotal role in the isolation of human retroviruses including HTLV-1 and HIV. The establishment of such a large panel of lines was aided by the development of defined media for culturing specific cell types. The lines are well characterized, and full clinical data are available for most of them. Many of the lines have been deposited with the American Type Culture Collection, Rockville, MD, where they are readily available for a modest handling fee. The lines have been widely distributed to investigators, and have had a major impact on biomedical research.


Linkage disequilibrium and genome-wide association analysis for anthocyanin pigmentation and fruit color in eggplant.
The genome-wide association (GWA) approach represents an alternative to biparental linkage mapping for determining the genetic basis of trait variation. Both approaches rely on recombination to re-arrange the genome, and seek to establish correlations between phenotype and genotype. The major advantages of GWA lie in being able to sample a much wider range of the phenotypic and genotypic variation present, in being able to exploit multiple rounds of historical recombination in many different lineages and to include multiple accessions of direct relevance to crop improvement. A 191 accessions eggplant (Solanum melongena L.) association panel, comprising a mixture of breeding lines, old varieties and landrace selections originating from Asia and the Mediterranean Basin, was SNP genotyped and scored for anthocyanin pigmentation and fruit color at two locations over two years. The panel formed two major clusters, reflecting geographical provenance and fruit type. The global level of linkage disequilibrium was 3.4 cM. A mixed linear model appeared to be the most appropriate for GWA. A set of 56 SNP locus/phenotype associations was identified and the genomic regions harboring these loci were distributed over nine of the 12 eggplant chromosomes. The associations were compared with the location of known QTL for the same traits. The GWA mapping approach was effective in validating a number of established QTL and, thanks to the wide diversity captured by the panel, was able to detect a series of novel marker/trait associations.


Light-driven novel properties of TiO2-modified polypropylene-based nanocomposite films.
Nanocomposite films obtained by TiO2 incorporation into a polypropylene (PP) polymer matrix were prepared via a straightforward melting process. The structural characteristics of the nanocomposite materials were examined by a multitechnique approach showing the outstanding morphological uniformity of the films. TiO2 incorporation into the polymer matrix renders self-sterilized and self-degradable materials which showed an impressive performance against gram-positive, gram-negative, coccus and yeast micro-organisms. Optimization of the novel properties of TiO2-PP nanocomposite films is reached with a 2 wt% of oxide content loading. The physico-chemical bases of this optimum are discussed.


Description of a new horned toad of Megophrys Kuhl & Van Hasselt, 1822 (Anura, Megophryidae) from southwest China.
A new species of the genus Megophrys is described from Guizhou Province, China. Molecular phylogenetic analyses supported the new species as an independent clade nested into the Megophrys. The new species could be distinguished from its congeners by a combination of the following characters: body size moderate (SVL 49.3-58.2 mm in males); vomerine ridges present distinctly, vomerine teeth present; tongue feebly notched behind; tympanum distinctly visible, oval; two metacarpal tubercles in hand; toes with one-third webbing and wide lateral fringes; heels overlapped when thighs are positioned at right angles to the body; tibiotarsal articulation reaching the level between tympanum and eye when leg stretched forward; an internal single subgular vocal sac present in male; in breeding male, the nuptial pads with large and sparse black nuptial spines present on the dorsal bases of the first two fingers.


Image-guided interstitial high-dose-rate brachytherapy in the treatment of metastatic esophageal squamous cell carcinoma.
To evaluate the efficacy of computed tomography (CT)- and magnetic resonance imaging (MRI)-guided interstitial high-dose-rate brachytherapy (HDR IBT = IBT) in patients with metastatic esophageal squamous cell carcinoma. Eleven patients with 21 unresectable metastases of histologically proven esophageal squamous cell carcinoma were included in this retrospective study. Fourteen visceral and 7 lung metastases were treated with image-guided (CT or open MRI guidance) IBT using a 192Iridium source (single fraction irradiation). Clinical and imaging follow-up were performed every 3 months after treatment. Primary endpoint was local tumor control (LTC) and safety. Furthermore, we analyzed safety, progression-free survival (PFS), and overall survival (OS). The median diameter of the target lesions was 2.2 cm (range: 0.7-6.8 cm), treated with a median D100 of 20.1 Gy (range: 10-25 Gy). During a median follow-up of 6.3 months (range: 3-21.8 months), three patients displayed local recurrences, resulting in LTC of 85.7%. Median PFS was 3.4 months and median OS after IBT was 13.7 months. No severe adverse events (grade 3+) requiring hospitalization or invasive intervention were recorded. Image-guided IBT is a safe and effective treatment in patients with metastasized esophageal squamous cell carcinoma.


Age differences in decision making under known risk: The role of working memory and impulsivity.
This study examined whether age differences in risky decision making are dependent on known probability and value of outcomes (i.e., the expected value [EV]), the valence of anticipated outcomes (gains or losses), and individual differences in working memory and impulsivity. We used a task that varied risk independently from EV so that taking risks could be advantageous or disadvantageous. Results indicated differential developmental courses for the sensitivity to EV and outcome valence from early to late adolescence. An increase in risk-advantageous but a decrease in risk-disadvantageous behavior was obtained between early-to-mid and late adolescence. All adolescents showed higher risky behavior when losses rather than gains were expected. Age differences in the sensitivity to EV were fully mediated by individual differences in working memory but not by self-reported impulsivity, suggesting that decision making under known risk is strongly limited by the maturation of cognitive control processes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Non invasive real-time monitoring of bacterial infection & therapeutic effect of anti-microbials in five mouse models.
In vivo imaging system has contributed significantly to the understanding of bacterial infection and efficacy of drugs in animal model. We report five rapid, reproducible, and non invasive murine pulmonary infection, skin and soft tissue infection, sepsis, and meningitis models using Xenogen bioluminescent strains and specialized in vivo imaging system (IVIS). The progression of bacterial infection in different target organs was evaluated by the photon intensity and target organ bacterial counts. Genetically engineered bioluminescent bacterial strains viz. Staphylococcus aureus Xen 8.1, 29 and 31; Streptococcus pneumoniae Xen 9 and 10 and Pseudomonas aeruginosa Xen-5 were used to induce different target organs infection and were validated with commercially available antibiotics. The lower limit of detection of colony forming unit (cfu) was 1.7-log10 whereas the lower limit of detection of relative light unit (RLU) was 4.2-log10 . Recovery of live bacteria from different target organs showed that the bioluminescent signal correlated to the live bacterial count. This study demonstrated the real time monitoring and non-invasive analysis of progression of infection and pharmacological efficacy of drugs. These models may be useful for pre-clinical discovery of new antibiotics.


An extension of the Jerger classification of tympanograms for ventilation tube patency--specification and evaluation of equivalent ear-canal volume criteria.
To determine ventilation tube (VT) patency, or presence of an eardrum perforation, where otoscopy is not available or corroboration is required, tympanometry may be used, with a firm acoustical rationale. However, published literature shows little evidence that tympanometric criteria for patency have been optimized or are in routine clinical use. A randomized trial of VTs in otitis media with effusion offered large case numbers, assessed by uniform protocol, to define and evaluate a tympanometric patency criterion. Children had been randomized to one of three interventions (VT insertion with or without adjuvant adenoidectomy and nonsurgical observation). The study examines 165 left and 171 right ears with functioning VTs and 103 left and 102 right noninserted ears, in children aged 3 3/4 to 7 1/4 yrs at first postintervention visit. Experienced otolaryngologists judged VT patency otoscopically. Measured equivalent ear-canal volume (Veq) was compared across the VT-inserted and the not-inserted groups, and also within the VT-inserted group between the pre- and postintervention visits. With otoscopy as reference, patency coding errors in both VT-inserted and not-inserted groups were analyzed as a function of Veq. Three methods of determining optimum cutoff were considered: equal error (cross-over point of the errors in each group), equated "cost" of error (maximum summed sensitivity and specificity), and minimum combined error (determined from the minimum of a polynomial fitted to the mean of the errors in each group). Cutoffs were evaluated in terms of classification accuracy against otoscopy after intervention. The between-group comparison gave cutoffs by the three methods at Veq > or = 0.95 mL, Veq > or = 1.10 mL, and Veq > or = 1.33 mL, respectively, pooled to 1.13 mL. The same 1.13 mL was also found for the within-group comparison. The corresponding cutoffs for the pre- and postintervention difference in Veq occurred at 0.23, 0.44, and 0.39 mL, respectively, with a mean of 0.35 mL. Within the range studied, age did not influence Veq, nor the optimum Veq cutoff, but boys had significantly larger Veqs (by 0.09 mL) than girls. Raw Veq, pre- and postintervention Veq difference or a combination of these definitions differed little in accuracy of predicting otoscopic status. In 3 3/4 to 7 1/4 years olds, the Veq criteria for VT patency, based on rigorous and transparent derivations, offer a supplementary information source for clinical practice, as well as a sole objective marker in research. We recommend for general use the pooled mean cutoff at Veq > or = 1.13 mL, slightly higher than the 1.00 mL in the literature. The pooled pre- and postintervention difference Veq criterion was slightly lower than the 0.4 mL of Shanks et al. However, the extra effort in its use, alone or in combination with raw Veq, was not justified. Given the wide (flat-bottomed) error functions, users have the option of declaring slightly lower or higher cutoffs, reflecting differing "costs" on the two types of errors, e.g. penalizing false "patent" decisions more heavily.


Estimates of inpatient admission rates and associated costs for infants before and after China's universal two-child policy.
China implemented a universal two-child policy in 2015. It is important to understand infants' medical utilization in the context of this policy to inform health policies and resource allocation. This study utilized a 20% random sample of administrative data from China's Urban and Rural Basic Medical Insurance (URBMI) in one of the largest southern Chinese cities from January 2015 to June 2018. Ordinary least squares models were used to estimate changes in inpatient admission rates and costs for infants between 0 and 6 months old after the implementation of China's universal two-child policy. The overall inpatient admission rate was 27.2% in 2015 and 31.3% in 2017. Compared with 2015, there was an increase in inpatient admission rates for infants 1 month old or younger (coef = 0.038, 95% CI = 0.029 to 0.047, p < .001) and infants 6 months old or younger (coef = 0.041, 95% CI = 0.030 to 0.052, p < .001) in 2017. The increase was larger for male infants than for female ones. The average inpatient admission cost was 8412.3 RMB ($1320.61) (SD = 15,088.2). There was no increase in inpatient admission costs overall. The average length of hospital stay was 7.3 days, the probability of going to a tertiary hospital was 76.2%, and the share of out-of-pocket costs was 53.0% for all diseases. After the implementation of the universal two-child policy in China, there was a significant increase in inpatient admission rates, especially for male infants. The overall associated costs did not change, but the increase in admission rates caused additional economic burdens for families and for social health insurance. Understanding the healthcare utilization of infants in the universal two-child period can provide insight for healthcare resource allocation in a time of dramatic changes in population policy.


Mechanical bowel preparation does not affect the intramucosal bacterial colony count.
The aim of this study was to determine if mechanical bowel preparation (MBP) influences the intramucosal bacterial colony count in the colon. Macroscopically normal colon mucosa was collected from 37 patients (20 with and 17 without MBP) who were undergoing elective colorectal surgery at three hospitals. The biopsies were processed and cultured in the same laboratory. Colony counts of the common pathogens Escherichia coli and Bacteroides as well as of total bacteria were conducted. The study groups were comparable with regard to age, gender, antibiotics use, diagnosis and type of resection. MBP did not influence the median colony count of E. coli, Bacteroides or total bacteria in our study. MBP did not affect the intramucosal bacterial count in this study. Further studies are suggested to confirm these findings.


Tobacco industry use of corporate social responsibility tactics as a sword and a shield on secondhand smoke issues.
The tobacco industry has used corporate social responsibility tactics to improve its corporate image with the public, press, and regulators who increasingly have grown to view it as a merchant of death. There is, however, an intractable problem that corporate social responsibility efforts can mask but not resolve: the tobacco industry's products are lethal when used as directed, and no amount of corporate social responsibility activity can reconcile that fundamental contradiction with ethical corporate citizenship. This study's focus is to better understand the tobacco industry's corporate social responsibility efforts and to assess whether there has been any substantive change in the way it does business with regard to the issue of exposure to secondhand smoke. The results show that the industry has made no substantial changes and in fact has continued with business as usual. Although many of the tobacco companies' tactics traditionally had been defensive, they strove for a way to change to a more offensive strategy. Almost without exception, however, their desire to appear to be good corporate citizens clashed with their aversion to further regulation and jeopardizing their legal position, perhaps an irreconcilable conflict. Despite the switch to offense, in 2006 a federal judge found the companies guilty of racketeering.


[Rounded atelectasis with emphasis on its wide spectrum].
While rounded atelectasis (RA) is considered to be rather common in the United States and Europe, the total number of RA cases reported from Japan still remains approximately 30. We have long been aware that there are many variations in the radiographic appearance of so-called RA and that RA has never been clearly defined. We retrospectively reviewed 22 cases collected as RA and its variants from several institutions. We defined RA as "peripheral atelectasis mimicking tumor secondary to shrinkage or bending of the pleura of various degrees, and accompanied by lung distortion." The diagnostic criteria of typical RA include (1) peripheral tumoral shadow in contact with pleural effusion or thickened pleura, (2) acute angle between the pleura and the shadow, (3) convergence of the pulmonary vessels and bronchi and (4) volume loss of the affected lobe. However, there are cases which lack some of these criteria but are considered to be included in the broad category of RA. We propose that RA should be considered to be an entity having a wide spectrum. Typical lesions showing "cranial tilting" of Hanke are on one side of the spectrum and small linear or strand shadows extending from the thickened pleura are on the other.


Prehospital continuous positive airway pressure for acute respiratory failure: the ACUTE feasibility RCT.
Acute respiratory failure is a life-threatening emergency. Standard prehospital management involves controlled oxygen therapy. Continuous positive airway pressure is a potentially beneficial alternative treatment; however, it is uncertain whether or not this treatment could improve outcomes in NHS ambulance services. To assess the feasibility of a large-scale pragmatic trial and to update an existing economic model to determine cost-effectiveness and the value of further research. (1) An open-label, individual patient randomised controlled external pilot trial. (2) Cost-effectiveness and value-of-information analyses, updating an existing economic model. (3) Ancillary substudies, comprising an acute respiratory failure incidence study, an acute respiratory failure diagnostic agreement study, clinicians perceptions of a continuous positive airway pressure mixed-methods study and an investigation of allocation concealment. Four West Midlands Ambulance Service hubs, recruiting between August 2017 and July 2018. Adults with respiratory distress and peripheral oxygen saturations below the British Thoracic Society's target levels were included. Patients with limited potential to benefit from, or with contraindications to, continuous positive airway pressure were excluded. Prehospital continuous positive airway pressure (O-Two system, O-Two Medical Technologies Inc., Brampton, ON, Canada) was compared with standard oxygen therapy, titrated to the British Thoracic Society's peripheral oxygen saturation targets. Interventions were provided in identical sealed boxes. Feasibility objectives estimated the incidence of eligible patients, the proportion recruited and allocated to treatment appropriately, adherence to allocated treatment, and retention and data completeness. The primary clinical end point was 30-day mortality. Seventy-seven patients were enrolled (target 120 patients), including seven patients with a diagnosis for which continuous positive airway pressure could be ineffective or harmful. Continuous positive airway pressure was fully delivered to 74% of participants (target 75%). There were no major protocol violations/non-compliances. Full data were available for all key outcomes (target ≥ 90%). Thirty-day mortality was 27.3%. Of the 21 deceased participants, 14 (68%) either did not have a respiratory condition or had ceiling-of-treatment decision implemented that excluded hospital non-invasive ventilation and critical care. The base-case economic evaluation indicated that standard oxygen therapy was probably cost-effective (incremental cost-effectiveness ratio £5685 per quality-adjusted life-year), but there was considerable uncertainty (population expected value of perfect information of £16.5M). Expected value of partial perfect information analyses indicated that effectiveness of prehospital continuous positive airway pressure was the only important variable. The incidence rate of acute respiratory failure was 17.4 (95% confidence interval 16.3 to 18.5) per 100,000 persons per year. There was moderate agreement between the primary prehospital and final hospital diagnoses (Gwet's AC1 coefficient 0.56, 95% confidence interval 0.43 to 0.69). Lack of hospital awareness of the Ambulance continuous positive airway pressure (CPAP): Use, Treatment Effect and economics (ACUTE) trial, limited time to complete trial training and a desire to provide continuous positive airway pressure treatment were highlighted as key challenges by participating clinicians. During week 10 of recruitment, the continuous positive airway pressure arm equipment boxes developed a 'rattle'. After repackaging and redistribution, no further concerns were noted. A total of 41.4% of ambulance service clinicians not participating in the ACUTE trial indicated a difference between the control and the intervention arm trial boxes (115/278); of these clinician 70.4% correctly identified box contents. Recruitment rate was below target and feasibility was not demonstrated. The economic evaluation results suggested that a definitive trial could represent value for money. However, limited compliance with continuous positive airway pressure and difficulty in identifying patients who could benefit from continuous positive airway pressure indicate that prehospital continuous positive airway pressure is unlikely to materially reduce mortality. A definitive clinical effectiveness trial of continuous positive airway pressure in the NHS is not recommended. Current Controlled Trials ISRCTN12048261. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 7. See the NIHR Journals Library website for further project information.


Interrupted work histories: retired women telling their stories.
The issue of women and work is a contemporary one which affects the private as well as the public sphere of women's lives. The social conditions which affect the present cohort of retired older women, have their roots in their work lives. In this article, we analyzed the oral histories of 7 retired women using a modified grounded theory approach to explore the long-term effects of having interrupted their work histories in order to care for family members. The core variable that emerged was the "valuing process" that occurred when these older women relieved their past experiences. We defined this as the relative merit that each participant attributed to her lifetime work achievements.


The interferon-inducible nucleolar p204 protein binds the ribosomal RNA-specific UBF1 transcription factor and inhibits ribosomal RNA transcription.
p204, a member of the interferon-inducible p200 family of murine proteins, is primarily nucleolar. We generated cell lines in which p204 was inducible by muristerone. This induction resulted in retardation of cell proliferation and inhibition of rRNA transcription in vivo. Interferon treatment, resulting in p204 induction and retardation of proliferation, also caused inhibition of rRNA transcription in vivo. p204 also inhibited rRNA transcription in vitro. This inhibition was overcome by addition of UBF1, the rRNA-specific transcription factor. A direct interaction between p204 and UBF1 was revealed in vitro in pull-down assays, and in vivo by co-immunoprecipitation from cell extracts. UBF1 bound strongly to at least two regions of p204: the N-terminal segment linked to the conserved 200 amino acid a segment, and the conserved 200 amino acid b segment. Cleavage of the a or b segments into two segments (encoded by single exons) resulted in a strong decrease or loss of binding. The inhibition of rRNA transcription by p204 may be due to the inhibition by p204 of the specific DNA binding of UBF1. This was revealed in electrophoretic mobility shift, magnetic bead and footprinting assays. Thus, p204 serves as a mediator of the inhibition of rRNA transcription by interferon.


Incidence of pulmonary thromboembolism (PTE) and new guidelines for PTE prophylaxis in Japan.
Incidence of venous thromboembolism (VTE), which had been considered a relatively rare disease in Japan, has been on the increase in recent years as eating habits have become more similar to those of the West. We have investigated the recent incidence data of perioperative pulmonary thromboembolism (PTE) in Japan and have established guidelines for the prevention of VTE. Recommended thromboprophylaxis is early ambulation for low risk group, elastic stocking (ES) or intermittent pneumatic compression (IPC) for moderate risk group, IPC or low dose unfractionated heparin (LDUH) for high risk group, and LDUH + IPC or LDUH + ES for highest risk group. The management fee for PTE prophylaxis was established and covered by health insurance in April 2004. Surprisingly, the incidence of perioperative PTE decreased just after this guideline was issued. After accumulation of further evidence and application of pharmacological agents, such as low molecular weight heparin, we will establish the advanced guidelines in the future.


Intussusception in Adults: A Rare Etiology of Small Intestinal Obstruction.
Small intestinal obstruction is a common surgical emergency that has a wide range of underlying etiologies. The most frequent causes of small intestinal obstruction include adhesions, hernias, and malignancies. The diagnosis of small intestinal obstruction is primarily dependent on the clinical findings, but imaging investigations are crucial to confirm the diagnosis and evaluate the complications. We report the case of a middle-aged woman with a complaint of abdominal pain for one week that was associated with abdominal distension and decreased bowel motion. Examination of the abdomen showed a distended abdomen. There was generalized tenderness, but no guarding or rigidity was noted. Initial laboratory investigation showed no derangement in the basic hematological and biochemical parameters. Abdominal CT was performed, which showed a segment of jejunojejunal intussusception causing a small intestinal obstruction. There was a well-defined, oval-shaped fat-attenuation mass lesion acting as a lead-point. Such radiological findings conferred the diagnosis of jejunojejunal intussusception due to jejunal lipoma. The patient underwent laparotomy, which confirmed the radiological finding. The intussusception was reduced, but a gangrenous intestine was observed. Resection of the affected intestine was performed, followed by a primary anastomosis. The patient recovered with no complications. Following the operation, oral feeding was started gradually according to the patient's tolerance. She was discharged after 10 days of hospitalization. At the follow-up visit after three months, the patient had no active symptoms. This case illustrated a rare etiology of small intestinal obstruction due to gastrointestinal lipoma. A computed tomography scan is strongly advised to reach the diagnosis and identify the lead points.


Why Malformations of Cortical Development Cause Epilepsy.
Malformations of cortical development (MCDs), a complex family of rare disorders, result from alterations of one or combined developmental steps, including progenitors proliferation, neuronal migration and differentiation. They are an important cause of childhood epilepsy and frequently associate cognitive deficits and behavioral alterations. Though the physiopathological mechanisms of epilepsy in MCD patients remain poorly elucidated, research during the past decade highlighted the contribution of some factors that will be reviewed in this paper and that include: (i) the genes that caused the malformation, that can be responsible for a significant reduction of inhibitory cells (e.g., ARX gene) or be inducing cell-autonomous epileptogenic changes in affected neurons (e.g., mutations on the mTOR pathway); (ii) the alteration of cortical networks development induced by the malformation that will also involve adjacent or distal cortical areas apparently sane so that the epileptogenic focus might be more extended that the malformation or even localized at distance from it; (iii) the normal developmental processes that would influence and determine the onset of epilepsy in MCD patients, particularly precocious in most of the cases.


Quantitation of phosphohistidine in proteins in a mammalian cell line by 31P NMR.
There is growing evidence to suggest that phosphohistidines are present at significant levels in mammalian cells and play a part in regulating cellular activity, in particular signaling pathways related to cancer. Because of the chemical instability of phosphohistidine at neutral or acid pH, it remains unclear how much phosphohistidine is present in cells. Here we describe a protocol for extracting proteins from mammalian cells in a way that avoids loss of covalent phosphates from proteins, and use it to measure phosphohistidine concentrations in human bronchial epithelial cell (16HBE14o-) lysate using 31P NMR spectroscopic analysis. Phosphohistidine is determined on average to be approximately one third as abundant as phosphoserine and phosphothreonine combined (and thus roughly 15 times more abundant than phosphotyrosine). The amount of phosphohistidine, and phosphoserine/phosphothreonine per gram of protein from a cell lysate was determined to be 23 μmol/g and 68 μmol/g respectively. The amount of phosphohistidine, and phosphoserine/phosphothreonine per cell was determined to be 1.8 fmol/cell, and 5.8 fmol/cell respectively. Phosphorylation is largely at the N3 (tele) position. Typical tryptic digest conditions result in loss of most of the phosphohistidine present, which may explain why the amounts reported here are greater than is generally seen using mass spectroscopy assays. The results further strengthen the case for a functional role of phosphohistidine in eukaryotic cells.


[Long-term care institutions for the elderly and their structural coupling with the surrounding social systems].
This study was performed in six Long-Term Care Institutions for the Elderly (LTCIEs) that helped low-income senior citizens in three regions of the country. Its aim is to examine how LTCIEs' internal organizational system maintained structural coupling with surrounding systems. The data were collected through interviews and observation. The analysis was based on concepts of Luhmann's Social Systems Theory. As a result, the rules of belonging did not encourage aid proposals that stimulated independent life and the individuality of residents. The structural couplings with the external environment generated negative resonance within LTCIEs, such as the lack of links to programmatic actions of public primary health care, inability to maintain a multiprofessional staff, inability to fully adapt the infrastructure, and inability to bring reçatives closer to the institution's daily routine. As a positive aspect, the staff was empowered by the presence of students and their professors.


Myotendinous pseudomasses: an imaging review.
A mass or a tumor may not always be an underlying cause for a clinically apparent swelling. A wide range of myotendinous disorders can present as pseudomasses. These include muscle/myofascial hernia, tendon tears, benign hypertrophy, accessory muscles, tendon xanthomas, diffuse myositis, and exertional compartment syndromes. We have briefly reviewed these lesions highlighting their typical radiological findings and have also highlighted the role of different imaging modalities and the role of dynamic imaging. Although rare, radiologists should be aware of these entities to avoid mislabeling a pseudomass as a mass or malignancy and to detect the abnormality in not-so-apparent masses.


Intermolecular disulfide bonds between nucleoporins regulate karyopherin-dependent nuclear transport.
Disulfide (S-S) bonds play important roles in the regulation of protein function and cellular stress responses. In this study, we demonstrate that distinct sets of nucleoporins (Nups), components of the nuclear pore complex (NPC), form S-S bonds and regulate nuclear transport through the NPC. Kinetic analysis of importin β demonstrated that the permeability of the NPC was increased by dithiothreitol treatment and reduced by oxidative stress. The permeability of small proteins such as GFP was not affected by either oxidative stress or a reducing reagent. Immunoblot analysis revealed that the oxidative stress significantly induced S-S bond formation in Nups 358, 155, 153 and 62 but not 88 and 160. The direct involvement of cysteine residues in the formation of S-S bonds was confirmed by mutating conserved cysteine residues in Nup62, which abolished the formation of S-S bonds and enhanced the permeability of the NPC. Knocking down Nup62 reduced the stress-inducible S-S bonds of Nup155, suggesting that Nup62 and Nup155 are covalently coupled via S-S bonds. From these results, we propose that the inner channel of the NPC is somehow insulated from the cytoplasm and is more sensitive than the cytoplasm to the intracellular redox state.


On-line two-dimensional LC: a rapid and efficient method for the determination of enantiomeric excess in reaction mixtures.
A novel LC-based method for the determination of enantiomeric excess (ee) in a sample mixture has been developed by employing on-line 2D LC. The orthogonal separation system is composed of an NH2 column as the first dimension to elute the target chiral compound from the crude mixture and a chiral column as the second dimension to determine the ee of the target chiral product. A series of crude mixtures from asymmetric reactions have been directly analyzed without prepurification. Good reproducibility (intra- and interday precisions were all under 1.33%) and good accuracy (deviations from ee values determined by 1D HPLC were all <1.03%) have been obtained. Compared with the traditional method for the determination of ee, on-line 2D HPLC can be used in real time and holds great potential in the time-saving determination of ee in asymmetric synthesis.


Kinetics of Accumulation of Ribulose-1,5-bisphosphate Carboxylase during Greening in Euglena gracilis: Photoregulation.
The preparation of a rabbit antibody to ribulose-1,5-bisphosphate carboxylase (RuBPCase) from Euglena gracilis and its use to quantitate RuBPCase in dark- and light-grown cells and during light-induced chloroplast development (greening) are described. Light-grown Euglena have at least 36 times more RuBPCase than dark-grown Euglena. Light is required for both the initiation and continued increase in net synthesis of RuBPCase over the dark level: brief illumination 12 hours before exposure to continuous light eliminates the lags in the accumulation and increase in activity of RuBPCase (as well as in chlorophyll accumulation); net synthesis is blocked in greening cells returned to the dark or exposed to 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Streptomycin or cycloheximide prevents RuBPCase accumulation when added at the beginning of greening but only partially blocks accumulation when added after 25 hours of greening. After 24 hours of greening, the activity of RuBPCase per milligram chlorophyll continues to increase slowly while concentration of the enzyme per milligram chlorophyll remains constant. This increased activity may be due to activation of the enzyme as well as to net synthesis.


Improved efficacy of alpha-particle-targeted radiation therapy: dual targeting of human epidermal growth factor receptor-2 and tumor-associated glycoprotein 72.
Human epidermal growth factor receptor-2 (HER-2) and tumor-associated glycoprotein 72 (TAG-72) have proven to be excellent molecular targets for cancer imaging and therapy. Trastuzumab, which binds to HER-2, is effective in the treatment of disseminated intraperitoneal disease when labeled with (213)Bi or (212)Pb. (213)Bi-humanized CC49 monoclonal antibody (HuCC49DeltaCH2), which binds to TAG-72, inhibits the growth of subcutaneous xenografts. A next logical step to improve therapeutic benefit would be to target tumors with both molecules simultaneously. Athymic mice bearing intraperitoneal human colon carcinoma xenografts were treated with a combination of trastuzumab and HuCC49DeltaCH2 labeled with (213)Bi administered through an intraperitoneal route. The sequence of administration also was examined. Before combining the 2 monoclonal antibodies, the effective doses of (213)Bi-CC49DeltaCH2 and (213)Bi-trastuzumab for the treatment of peritoneal disease were determined to be 500 muCi for each labeled antibody. Treatment with (213)Bi-HuCC49DeltaCH2 resulted in a median survival of 45 days and was comparable to the median survival achieved with (213)Bi-trastuzumab. Each combination provided greater therapeutic efficacy than either of the agents given alone. However, the greatest therapeutic benefit was achieved when (213)Bi-HuCC49DeltaCH2 and (213)Bi-trastuzumab were coinjected, and a median survival of 147 days was obtained. Dual targeting of 2 distinct molecules in tumors such as TAG-72 and HER-2 with alpha-particle radiation resulted in an enhanced, additive, therapeutic benefit. The authors also observed that this radioimmunotherapeutic strategy was well tolerated.


Intraluminal papaverine with pH 3 doubles blood flow in the internal mammary artery.
Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive injections of papaverine solution or isotonic saline or no injection into the left internal mammary artery (LIMA) used as graft. Blood flow in the LIMA was measured twice-after dissection of the pedicle and before anastomosis to the coronary artery. Blood flow increased significantly in all three groups, but after papaverine injection it was twice as high as in the control groups, increasing by 285% (from 40 +/- 12 to 154 +/- 32 ml/min, p = < 0.0001). The pH of the papaverine solution was only 3, and we advise that surgeons check and correct pH in the papaverine solutions they use, in order to avoid endothelial damage to the LIMA. Based on these results we can recommend papaverine injection into the arterial graft only if the initial flow is low.


Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry.
We report the application of tandem mass spectrometry to prospective newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. MCAD deficiency is diagnosed from dried blood spots on filter paper cards from newborns on the basis of the increase of medium chain length acylcarnitines identified by isotope dilution mass spectrometry methods. A robust and accurate semiautomated method for the analysis of medium chain length acylcarnitines as their butyl esters was developed and validated. Quantitative data from the analyses of 113 randomly collected filter paper blood spots from healthy newborns showed low concentrations of medium chain length acylcarnitines such as octanoylcarnitine. The maximum concentration of octanoylcarnitine was 0.22 mumol/L, with the majority being at or below the detection limit. In all 16 blood spots from newborns with confirmed MCAD deficiency, octanoylcarnitine was highly increased [median 8.4 mumol/L (range 3.1-28.3 mumol/L)], allowing easy detection. The concentration of octanoylcarnitine was significantly higher in these 16 newborns (< 3 days of age) than in 16 older patients (ages 8 days to 7 years) with MCAD deficiency (median 1.57 mumol/L, range 0.33-4.4). The combined experience of prospective newborn screening in Pennsylvania and North Carolina has shown a disease frequency for MCAD deficiency of 1 in 17,706. No false-positive and no known false-negative results have been found. A validated method now exists for prospective newborn screening for MCAD deficiency.