Conservation, diversification and expansion of C2H2 zinc finger proteins in the Arabidopsis thaliana genome.
The classical C2H2 zinc finger domain is involved in a wide range of functions and can bind to DNA, RNA and proteins. The comparison of zinc finger proteins in several eukaryotes has shown that there is a lot of lineage specific diversification and expansion. Although the number of characterized plant proteins that carry the classical C2H2 zinc finger motifs is growing, a systematic classification and analysis of a plant genome zinc finger gene set is lacking. We found through in silico analysis 176 zinc finger proteins in Arabidopsis thaliana that hence constitute the most abundant family of putative transcriptional regulators in this plant. Only a minority of 33 A. thaliana zinc finger proteins are conserved in other eukaryotes. In contrast, the majority of these proteins (81%) are plant specific. They are derived from extensive duplication events and form expanded families. We assigned the proteins to different subgroups and families and focused specifically on the two largest and evolutionarily youngest families (A1 and C1) that are suggested to be primarily involved in transcriptional regulation. The newly defined family A1 (24 members) comprises proteins with tandemly arranged zinc finger domains. Family C1 (64 members), earlier described as the EPF-family in Petunia, comprises proteins with one isolated or two to five dispersed fingers and a mostly invariant QALGGH motif in the zinc finger helices. Based on the amino acid pattern in these helices we could describe five different signature sequences prevalent in C1 zinc finger domains. We also found a number of non-finger domains that are conserved in these families. Our analysis of the few evolutionarily conserved zinc finger proteins of A. thaliana suggests that most of them could be involved in ancient biological processes like RNA metabolism and chromatin-remodeling. In contrast, the majority of the unique A. thaliana zinc finger proteins are known or suggested to be involved in transcriptional regulation. They exhibit remarkable differences in the features of their zinc finger sequences and zinc finger arrangements compared to animal zinc finger proteins. The different zinc finger helix signatures we found in family C1 may have important implications for the sequence specific DNA recognition and allow inferences about the evolution of the members in this family.


[Antibiotic resistance in Streptococcus pneumoniae strains isolated from sterile body sites].
Antibiotic resistance in Streptococcus pneumoniae has become an important issue in the last years. Penicillin resistance rates vary among countries and among different regions in countries. It is important to know penicillin resistance rates among isolates, in planning empirical antimicrobial therapy in pneumococcal infections. In this study, the antibiotic resistance rates of S. pneumoniae strains isolated from sterile body sites were investigated with both E-test and disc diffusion methods for penicillin, erythromycin, levofloxacin, and with only disc diffusion method for chloramphenicol, ceftriaxone, vancomycin, rifampin, trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, and tetracycline. A total of 165 strains were included into the study of which 52 were isolated from blood, 46 from cerebrospinal fluids, 25 from pleural fluids, 24 from dacryocystitis materials, 13 from tympanocentesis materials, 3 from joint fluids and 2 from wound specimens. Intermediate resistance to penicilin was 18.8%, while the resistance rates to TMP-SMX, tetracycline, chloramphenicol, erythromycin and levofloxacin were detected as 21.2%, 10.9%, 9.7%, 5.4% and 0.6%, respectively. None of the isolates were highly resistant to penicillin, nor resistant to vancomycin, ceftriaxone and rifampin. In conclusion, penicillin is still the first line therapeutic agent for pneumococcal infections except for severe infections such as meningitis, in our region.


Comparison of annual percentage change in breast cancer incidence rate between Taiwan and the United States-A smoothed Lexis diagram approach.
Recent studies compared the age effects and birth cohort effects on female invasive breast cancer (FIBC) incidence in Asian populations with those in the US white population. They were based on age-period-cohort model extrapolation and estimated annual percentage change (EAPC) in the age-standardized incidence rates (ASR). It is of interest to examine these results based on cohort-specific annual percentage change in rate (APCR) by age and without age-period-cohort model extrapolation. FIBC data (1991-2010) were obtained from the Taiwan Cancer Registry and the U.S. SEER 9 registries. APCR based on smoothed Lexis diagrams were constructed to study the age, period, and cohort effects on FIBC incidence. The patterns of age-specific rates by birth cohort are similar between Taiwan and the US. Given any age-at-diagnosis group, cohort-specific rates increased overtime in Taiwan but not in the US; cohort-specific APCR by age decreased with birth year in both Taiwan and the US but was always positive and large in Taiwan. Given a diagnosis year, APCR decreased as birth year increased in Taiwan but not in the US. In Taiwan, the proportion of APCR attributable to cohort effect was substantial and that due to case ascertainment was becoming smaller. Although our study shows that incidence rates of FIBC have increased rapidly in Taiwan, thereby confirming previous results, the rate of increase over time is slowing. Continued monitoring of APCR and further investigation of the cause of the APCR decrease in Taiwan are warranted.


Low-temperature, solution-processed hole selective layers for polymer solar cells.
A new method is reported for preparing solution-processed molybdenum oxide (MoO(3)) hole selective layer (HSL). Via combustion processing at low annealing temperatures, the obtained MoO(3) HSL exhibits a high charge-transporting performance similar to poly(ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) but overcoming its defect to device stability. The combustion precursor solution using ammonium heptamolybdate as the metal source, acetylacetone as a 'fuel', and nitric acid as an oxidizer can largely reduce the temperature for transformation of the polyoxomolybdate to α-phase MoO(3). Furthermore, when a small amount of PEDOT:PSS has been introduced into the combustion precursor solution to improve the film morphology, the derived film can exhibit a flat and continuous surface morphology with coexistence of α- and β-MoO(3) after being annealed at a low temperature (150 °C). The simplicity, rapidness, and effectiveness of our method together with the low annealing temperature needed make it promising for the roll-to-roll manufacture of polymer solar cells.


Clinical validation of the Preterm Oral Feeding Readiness Assessment Scale.
Health professionals have great difficulties to establish the adequate and safe time to start breast feeding in preterm infants. There is a need to develop a standardized tool to help health professionals to comprehensively evaluate preterm infant readiness to transition preterm infants' feeding from gastric to oral, and encourage breast feeding practice in neonatal units. To clinical validate the accuracy of a Preterm Oral Feeding Readiness Assessment Scale with 60 clinically stable preterm infants. Global accuracy, sensitivity and specificity of Preterm Oral Feeding Readiness Assessment Scale cut-offs, compared to milk intake through translactation, were estimated through ROC curves (Receiver Operating Characteristic Curves). The global accuracy of Preterm Oral Feeding Readiness Assessment Scale was 74.38%. The highest sensitivity and specificity were obtained for three cut-offs: 28, 29 and 30. Since higher specificity (75.68%) for the Preterm Oral Feeding Readiness Assessment Scale was found at a score cut-off=of 30 showed higher specificity (75.68%), it should be used as a cut-off score to select initiate breastfeeding the preterm newborns' oral feeding readiness. The Preterm Oral Feeding Readiness Assessment Scale is considered valid to assist health professionals to initiate preterm feeding in view of promoting safe and objective breastfeeding.


Comparative effectiveness of flossing and brushing in reducing interproximal bleeding.
This study assesses the comparative effectiveness of three types of dental floss and toothbrushing in reducing interproximal bleeding sites, measured by stimulation with wooden interdental cleaners using the interdental bleeding index assessment method. The 119 adult subjects with gingival inflammation were randomly assigned to one of four groups at the beginning of a supervised 2 week clinical trial. The toothbrushing only group achieved a 35% reduction in bleeding sites and the three flossing groups all demonstrated dramatic reductions of about 67%. The three varieties of dental flosses were about equally effective in reducing interproximal bleeding and doubly effective as toothbrushing alone. Compared to probing, the interdental bleeding index method is considered a simplified method of assessing interproximal gingival inflammation.


Inhibition of autophagy at a late stage enhances imatinib-induced cytotoxicity in human malignant glioma cells.
Malignant gliomas are common primary tumors of the central nervous system. The prognosis of patients with malignant glioma is poor in spite of current intensive therapy and thus novel therapeutic modalities are necessary. Imatinib mesylate, a tyrosine kinase inhibitor, is effective in the therapy of tumors including leukemias but not as a monotherapy for malignant glioma. Recently, it is thought that the adequate modulation of autophagy can enhance efficacy of anticancer therapy. The outcome of autophagy manipulation, however, seems to depend on the autophagy initiator, the combined stimuli, the extent of cellular damage and the type of cells, and it is not yet fully understood how we should modulate autophagy to augment efficacy of each anticancer therapy. In this study, we examined the effect of imatinib with or without different types of autophagy inhibitors on human malignant glioma cells. Imatinib inhibited the viability of U87-MG and U373-MG cells in a dose dependent manner and caused nonapoptotic autophagic cell death. Suppression of imatinib-induced autophagy by 3-methyladenine or small interfering RNA against Atg5, which inhibit autophagy at an early stage, attenuated the imatinib-induced cytotoxicity. In contrast, inhibition of autophagy at a late stage by bafilomycin A1 or RTA 203 enhanced imatinib-induced cytotoxicity through the induction of apoptosis following mitochondrial disruption. Our findings suggest that therapeutic efficiency of imatinib for malignant glioma may be augmented by inhibition of autophagy at a late stage, and that appropriate modulation of autophagy may sensitize tumor cells to anticancer therapy.


Assessment of the Effect of Solid Waste Dump Site on Surrounding Soil and River Water Quality in Tepi Town, Southwest Ethiopia.
An increase in urban population and the rising demand for food and other essentials perpetuate a rise in the amount of waste being generated daily by each household. In Ethiopia, this waste is eventually thrown into open dump sites. It can cause severe impact on soil and surface water quality. As a result, it becomes the probable source of human health risk through food chain. Therefore, this study was aimed at assessing the effect of a solid waste dump site on surrounding soil and river water quality in Tepi town, Southwest Ethiopia. Three surface water, one leachate, and four soil samples were collected and analyzed. Six heavy metals for surface water and leachate samples and four heavy metals for soil samples were measured by flame atomic absorption spectroscopy. In addition, physiochemical parameters were analyzed using standard methods. The data were analyzed statistically using Origin pro version 8.0 computer software packages. The pH of soil was slightly basic ranging from 8 ± 0.1 to 8.7 ± 0.21. Electrical conductivity was lower at 60 meters (1800 ± 0.5 μs/cm) and higher in the other sample sites (3490 ± 0.66-4920 ± 1.04 μs/cm). The concentration of heavy metals in soil samples revealed cadmium (0.53 ± 0.01-2.26 ± 0.02 mg/kg), zinc (623.93 ± 0.29-859.41 ± 0.02 mg/kg), lead (3.26 ± 0.25-57.560.26 mg/kg), and copper (204.06 ± 0.06-337.11 ± 0.01 mg/kg). Lead, cadmium, manganese, nickel, copper, and zinc were found in the leachate water; nickel and manganese were found in the nearby river water; BOD5 and COD for both leachate and stream water samples were found to be higher than standard guideline values. The finding suggested that solid waste open dump site adversely affects soil and water quality in the study area and becomes a probable source of risk for human health via the food chain.


Deciding on route of delivery for obese women with a prior cesarean delivery.
This study was undertaken to estimate the vaginal birth after cesarean (VBAC) success rate, compare rates of infections in women attempting VBAC and those undergoing planned repeat cesarean, and compare the cost of these two plans of care for obese women. We performed a historical cohort analysis of singleton deliveries at >/=36 weeks' gestation in women with a body mass index 40 or greater and one prior cesarean delivery. Outcomes included rates of VBAC success and puerperal infections and mean cost of care. The cohort consisted of 122 mother-infant pairs, 61 each in the VBAC and cesarean groups. In the VBAC group, 57% (95% CI 45-70) of women were delivered vaginally. The VBAC group had higher rates of chorioamnionitis (13.1% vs 1.6%, P=.02), endometritis (6.6% vs 0%, P=.06), and composite puerperal infection (24.6% vs 8.2%, P=.01). Mean cost of care was similar for mothers ($4439 vs $4427, P=.95), infants ($1241 vs $1422, P=.49), and mother-infant pairs ($5680 vs $5851, P=.64). Compared with planned cesarean delivery, VBAC trials in obese women are three times as likely to be complicated by infection and do not result in reduced costs.


Therapeutic Development of Mesenchymal Stem Cells or Their Extracellular Vesicles to Inhibit Autoimmune-Mediated Inflammatory Processes in Systemic Lupus Erythematosus.
Since being discovered over half a century ago, mesenchymal stem cells (MSCs) have been investigated extensively to characterize their cellular and physiological influences. MSCs have been shown to possess immunosuppressive capacity through inhibiting lymphocyte activation/proliferation and proinflammatory cytokine secretion while simultaneously demonstrating limited allogenic reactivity, which subsequently led to the evaluation of therapeutic feasibility to treat inflammatory diseases. Although regulatory constraints have restricted MSC development pharmacologically, limited clinical studies have shown encouraging results using MSC infusions to treat systemic lupus erythematosus (SLE); but, more trials will have to be performed to conclusively determine the clinical efficacy of MSCs to treat SLE. Moreover, there are some data to suggest that MSCs possess tumorigenic potential and that the immunosuppressive influence can be dramatically affected by both donor variability and ex vivo expansion. Given that recent studies have found that the immunosuppressive effects of MSCs are a result, at least in part, to extracellular vesicle (EV) secretion, the use of MSC-derived EVs has been suggested as a cell-free therapeutic alternative. Despite the positive data observed using EVs isolated from human MSCs to suppress inflammatory responses in vitro and in inhibiting autoimmune disease pathogenesis in preclinical work, there are no studies to date examining EVs from MSCs to treat SLE in humans or animal models. Considering that EVs are not subject to the strict regulatory constraints of stem cell-based pharmacological development and are more readily standardized with regard to industrial-scale production and storage, this review outlines the anti-inflammatory biology of MSCs and the scientific evidence supporting the potential use of EVs derived from human MSCs to treat patients with SLE.


Expression of a fungal cellobiohydrolase in insect cells.
The gene for Trichoderma reesei cellobiohydrolase I (CBHI) was expressed with a recombinant baculovirus and high levels of secreted protein were produced in Spodoptera frugiperda and Trichoplusia ni insect cells. Electrophoretic analysis indicated that the recombinant CBHI (rCBHI) was similar in apparent molecular weight to the native form and immunoblotting with anti-CBHI monoclonal antibodies confirmed its identity. The rCBHI was easily purified by affinity and hydrophobic interaction chromatography and demonstrated enzymatic activity on soluble substrate.


Xenobiotic metabolism in the nasal epithelia.
The nasal epithelia in several species contains fairly high levels of drug metabolising enzymes, and in many cases the site specific toxicities of chemicals are due to their metabolic activation in the nasal tissues. This article reviews some of the current literature on the metabolic capacities of nasal epithelia, in particular the distribution and characteristics of cytochrome P-450 isozymes. In addition to the role of these nasal enzymes in metabolism of inhaled xenobiotics, other possible biological roles for these enzymes are also discussed.


Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.
Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1β, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.


Affect and psychiatric symptoms in a veteran polytrauma clinic.
Although the relationship between negative affect and psychiatric symptoms has been well-demonstrated in research, less is known about positive affect relative to negative affect, and its relationship to psychiatric symptoms, especially among veterans. This study examined how levels of positive and negative affect are associated with symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD). Data were collected in a veteran polytrauma clinic; analyses were conducted using data from 94 veterans (87 males) with and without a mild traumatic brain injury (mTBI) diagnosis. Results demonstrate that positive and negative affect were separate dimensions and that both were independently related to each symptom measure. After removing the contribution of negative affect from symptom reports, strong relationships remained between positive affect and psychiatric symptoms. Furthermore, the magnitude of the associations for positive affect and for negative affect with symptoms of depression, anxiety, and PTSD were not impacted by a mTBI diagnosis. Altogether, findings suggest that both positive and negative affect should be uniquely considered when conceptualizing, assessing, and treating returning service members; in addition, positive affect may be an appropriate target of assessment and interventions of persons who have experienced polytrauma.


[Investigation of drug-resistance to rifampin and rpoB gene sequence analysis of Mycobacterium abscessus].
To observe the resistance of Mycobacterium abscessus to rifampin and to investigate if there is any mutation of rpoB gene in strains with high minimal inhibitory concentration (MIC). Mycobacterium abscessus was identified with both biochemical methods and PCR-RFLP. The MICs of rifampin to all the clinical strains and the type strain ATCC19977 were determined. DNA sequences were obtained from a 1272 bp fragment of the rpoB gene from either low or high rifampin MIC strains using PCR amplification. Only one strain had low MICs of 4 microg/ml. MICs of all the other 14 strains, as well as the type stain were above 128-256 microg/ml. Although there were some differences in nucleotide sequence of rpoB gene, all strains had the same amino acid sequence without any mutations. Mycobacterium abscessus showed a high resistance to rifampin. Mutations of rpoB gene do not seem to be the responsible mechanism.


Megakaryocytes with intracytoplasmic blood cells.
The phenomenon of megakaryocytes containing intracytoplasmic blood cells was frequently observed in the bone marrow of rats. The frequency appeared to increase in inflammatory or neoplastic conditions. The types of blood cells engulfed were mainly neutrophils. For the first time, megakaryocytes also were found to be engulfed.


Ovarian drilling down-regulates endometrial nuclear factor-κB p65 expression in women with PCOS: A prospective case-control study.
To investigate the impact of laparoscopic ovarian drilling (LOD) on the expression of endometrial NFκB p65 (Rel A) in women with clomiphene-resistant polycystic ovary syndrome (PCOS). The study group comprised 25 normal-weight women with PCOS undergoing LOD and 14 control women without PCOS. Endometrial NF-κB p65 levels evaluated before and after LOD following immunohistochemical staining. The semiquantitative method was used to evaluate the intensity of NF-κB p65 levels. NF-κB p65 was found to higher in the endometrium of patients with PCOS compared to controls. LOD leads to significant down-regulation in endometrial NF-κB p65 expression. NF-κB p65 expression of PCOS and fertile control were similar after LOD. After LOD, H-score values decreased approximately 3-fold. The H-score of the control subjects was lower than the preoperative and postoperative H-score values of the control women with ovarian cyst. Expression of endometrial NF-κB p65 did not change following ovarian cystectomy. The laterality of the ovarian cyst did not cause any change in preoperative H-score values. By downregulating the endometrial NF-κB p65 expression LOD improved physiological inflammation in women with PCOS.


Internet addiction associated with right pars opercularis in females.
Structural differences in higher-order brain areas are common features of behavioral addictions, including Internet addiction (IA) as well. Taking into consideration the limited number of studies and methods used in previous studies on IA, our aim was to investigate the correlates of IA and the morphometry of the frontal lobes. To observe these relationships, the high-resolution T1-weighted MR images of 144 healthy, Caucasian, university students were analyzed with volumetry and voxel-based morphometry. The Problematic Internet Use Questionnaire (PIUQ) was used to assess IA. We found significant correlations between PIUQ subscales and the volume of the right pars opercularis volume and gray matter mass in women. The increased gray matter measures of this structure might be explained with the extended effort to control for the impulsive behavior in addiction, and with the increased number of social interactions via the Internet.


Regional odontodysplasia: report of a case.
Regional odontodysplasia is a rare developmental anomaly involving both mesodermal and ectodermal dental components in groups of contigous teeth. RO affects the primary and permanent dentition in the maxilla and mandible or both jaws. Generally, it is localized in only one arch. The maxillary arch is affected more often than the mandibular arch. The affected teeth tend to be in a consecutive series that does not cross the midline, although some cases do not follow this pattern, as in the present case, have been documented. Radiogaphically wide pulp chambers and thin poorly defined hard tissue outlines described as a "ghost teeth" appearance, are typical features. A case of regional odontodysplasia in a 5 year old male patient is presented. The clinical and radiogaphical findings of this developmental anomaly and treatment are described.


The effect of various avocado oils on skin collagen metabolism.
The effects of various avocado oils on collagen metabolism in skin were studied in growing rats fed diets containing 10% (w/w) of the tested oils. Rats fed the unrefined avocado oil extracted with hexane from the intact fruit, its unsaponifiables or the avocado seed oil, showed significant increases in soluble collagen content in skin, though total collagen content was not affected. The increased soluble collagen content appears to be a consequence of the inhibition of lysyl oxidase activity. The active factor was found to be present in the unrefined avocado oil and probably originated from the avocado seed, since collagen metabolism was affected only by fractions which contained lipids fraction from the seed. In comparison rats fed the refined or unrefined soybean oils showed no effects.


Intake and sources of gluten in 20- to 75-year-old Danish adults: a national dietary survey.
Celiac disease, an immunological response triggered by gluten, affects ~1 % of the Western population. Information concerning gluten intake in the general population is scarce. We determined intake of gluten from wheat, barley, rye and oat in the Danish National Survey of Diet and Physical Activity 2005-2008. The study population comprised a random cross-sectional sample of 1494 adults 20-75 years, selected from the Danish Civil Registration System. Protein content in wheat, rye, barley and oat was determined from the National Danish Food Composition Table and multiplied with the amount of cereal used in recipes. Amount of gluten was calculated as amount of cereal protein ×0.80 for wheat and oat, ×0.65 for rye and ×0.50 for barley. Dietary intake was recorded daily during seven consecutive days in pre-coded food diaries with open-answer possibilities. Mean total gluten intake was 10.4 ± 4.4 g/day (10th-90th percentiles; 5.4-16.2 g/day), in men 12.0 ± 4.6 g/day and 9.0 ± 3.4 g/day in women. It was higher among men than among women in all age groups (20-75 years; P < 0.0001); however, this difference was eliminated when adjusting for energy intake. Intake of different gluten sources tended to be higher in men than in women with the exception of gluten from barley. Total gluten intake decreased with increasing age (P < 0.0001) as did gluten intake from wheat (P < 0.0001), whereas intake of gluten from rye (P < 0.0001) and barley (P = 0.001) increased with increasing age, also when adjusted for energy intake or body weight. This study presents representative population-based data on gluten intake in Danish adults. Total gluten intake decreased with increasing age.


[Correlation analysis between biochemical and biophysical markers of endothelium damage in children with diabetes type 1].
Endothelial damage is one of the earliest stages in the atherosclerosis process. Adhesion molecules, secreted from dysfunctional endothelial cells are considered as early markers of atherosclerotic disease. Ultrasonographic evaluation of brachial arteries serves to detect biophysical changes in endothelial function, and evaluation of carotid arteries intima-media thickness allows to evaluate the earliest structural changes in the vessels. The aim of the study was to the evaluate levels of selected adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin) and endothelial function with use of brachial artery dilatation study (flow mediated dilation--FMD, nitroglycerine mediated dilation--NTGMD) and IMT in carotid arteries in children and adolescents with diabetes type 1, as well as the correlation analysis between biochemical and biophysical markers of endothelial dysfunction. We studied 76 children and adolescents, with mean age--15.6+/-2.5 years, suffering from diabetes mean 7.8+/-2.8 years, mean HbA1c--8.4+/-1.5%. Control group consisted of 33 healthy children age and gender matched. Adhesion molecules levels were estimated with the use of immunoenzymatic methods (R&D Systems). Endothelial function was evaluated by study of brachial arteries dilation--FMD, NTGMD, with ultrasonographic evaluation (Hewlett Packard Sonos 4500) after Celermajer method, and IMT after Pignoli method. In the study group we found elevated levels of sICAM-1: 309.54+/-64 vs. 277.85+/-52 ng/ml in the control group (p<00.05) and elevated level of sE-selectin: 87.81+/-35 vs. 66.21+/-22 ng/ml (p<00.05). We found significantly impaired FMD in brachial arteries in the study group--7.51+/-4.52 vs. 12.61+/-4.65% (p<00.05) and significantly higher IMT value: 0.51+/-0.07 vs. 0.42+/-0.05 mm (p<00.001). Correlation analysis revealed a significant negative correlation between sE-selectin and FMD - r=-0.33 (p=0.004), and a positive correlation between E-selectin and IMT: r=0.32 (p=0.005). 1. In children and adolescents with diabetes type 1 we found elevated levels of adhesion molecules sICAM-1 and sE-selectin, what can confirm an endothelial dysfunction in these patients. 2. Significant negative correlation between sE-selectin level and FMD, and positive correlation between sE-selectin and IMT were found. 3. Biophysical proof of this damage is impaired brachial artery dilatation--FMD, and increased IMT values provide information about structural changes in the vessels.


Risk factors for Thoroughbred racehorse fatality in flat starts in Victoria, Australia (1989-2004).
Research into risk factors specific for fatality in flat racing should be focused at a regional level as the risk factors may differ among countries and even regions within countries. To identify risk factors for fatality of Thoroughbred racehorses in flat starts on all racecourses in Victoria, Australia between 1989 and 2004. Fatalities comprised all horses that died during or immediately after a flat race or official flat trial, and all horses that were subjected to euthanasia within 24 h of an event in which an injury was sustained. The retrospective study involved 283 case starts and 3307 control starts. Univariable and multivariable backward stepwise logistic regression was used to identify risk factors for fatality at any one start. In the final multivariable model, horse gender, prior racing history, race length, racing year, racecourse location and track rating were associated with fatality. This study identified specific risk factors for fatality. The findings are consistent with the hypothesis that horses accumulating high speed exercise are predisposed to catastrophic injury. The study has also highlighted the need to investigate further the adverse effects of different track ratings on the incidence of injury and subsequent fatality. The results will facilitate the development of effective strategies to improve overall safety of horses and jockeys in flat racing in Victoria, Australia.


Systemic lupus erythematosus in Denmark: clinical and epidemiological characterization of a county-based cohort.
A population based cohort of patients with systemic lupus erythematosus (SLE) was recruited from a for epidemiological purposes representative Danish region. Patients were ascertained from 4 different sources with a high degree of completeness as estimated by using capture-recapture analysis. The diagnosis was verified by means of case records, patient interviews, and clinical examinations. Patients were classified according to the 1982 revised ACR criteria as Definite SLE (D-SLE) fulfilling > or = 4 criteria and Incomplete SLE (I-SLE) with < 4 criteria. As of January 1, 1995, the point prevalences of D-SLE and I-SLE were 21.7 and 5.2 per 100000 respectively. The cohort comprised 98% white Europeans. The annual incidence of D-SLE increased from 1.0/100,000 to 3.6/100,000 during the study period 1980-94. D-SLE patients had clinical profiles comparable to other Western European study populations. The I-SLE subclass had milder disease manifested by lower criterial load and absence of cerebral and kidney involvement. Tissue and organ damage expressed as SLICC-score increased in the order of live I-SLE, live D-SLE, and deceased patients.


Preparation of (111)In-DTPA morpholino oligomer for low abdominal accumulation.
An ability to quantitate the beta cell mass by noninvasive nuclear imaging will be very useful in the prevention, diagnosis, and treatment of diabetes. However, to be successful, radioactivity from the pancreas must not be obscured by the background radioactivity in the abdomen. Pretargeting offers the promise of achieving high target organ to normal tissue ratios. In preparation for pancreas imaging studies by pretargeting using morpholino oligomers (MORF/cMORF), it was necessary to develop a simple and efficient method to radiolabel the cMORF effector. Because we have shown that labeling the cMORF with (111)In via DTPA reduces excretion into the intestines compared to labeling with (99m)Tc via MAG(3), the conjugation of DTPA to cMORF was investigated for (111)In labeling. The amine-derivatized cMORF was conjugated with DTPA using 1-ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) as an alternative to the conventional cyclic anhydride. The conjugation efficiency (represented by the number of DTPA groups attached per cMORF) was investigated by changing the EDC, DTPA, and cMORF molar ratios. Different open columns were considered for the purification of DTPA-cMORF. Before conjugation, each cMORF molecule was confirmed to have an amine by trinitrobenzene sulfonic acid (TNBS) assay using the omega-amino butyric acid as positive standard and the non-amine derivatized cMORF as negative standard. The average number of DTPA groups per cMORF was 0.15-0.20 following the conjugation over a cMORF/DTPA molar ratio of 0.5-5 and over a cMORF/EDC molar ratio of 20-60. The conjugation efficiency was lower than expected probably due to steric hindrance. A 1 x 50cm P-4 column using ammonium acetate as eluting buffer provided an adequate separation of DTPA-cMORF from free DTPA. The (111)In labeling efficiency by transchelation from acetate exceeded 95%, thus avoiding the need for postlabeling purification. Despite the lower than expected conjugation efficiency in which no more than one-fifth of the cMORF were DTPA-derivatized, a specific radioactivity of at least 300microCi/microg or 1.90Ci/micromol of cMORF was achieved. In conclusion, a protocol is described for (111)In-DTPA-cMORF that provides the high specific activity favorable to beta cell imaging because of the low mass fraction of beta cells in pancreas (1-2%) and obviates the need for postlabeling purification.


Abdominal wall endometriosis: report of two cases.
Endometriosis is the abnormal existence of functional uterine mucosal tissue outside the uterus. It is a usual disorder of women in reproductive age, which is mainly located in the female genital tract. We report the cases of two women with endometriosis of the abdominal wall; the first one in the rectus abdominis muscle and the second one in the surgical scar of previous caesarian incision. The diagnosis was made by the histopathological analysis of the surgical specimens.


The importance of timing of heat events for predicting the dynamics of aphid pest populations.
Heatwaves are increasing in frequency and there is growing interest in their impact on pest organisms. Previous work indicates that effects depend on the timing of the stress event, whose impact needs to be characterized across the full set of developmental stages and exposure periods of an organism. Here, we undertake such a detailed assessment using heat stress (20-35 °C diurnal cycle) across the nymph and adult stages of the English grain aphid, Sitobion avenae (Fabricius). Stress-related mortality increased with stress duration at all stages; effects were less severe at the late nymphal stage. Effects on longevity adults after stress showed a complex pattern with nymphal heat stress, increasing with stress duration at the late nymphal stage, but decreasing with duration at the early nymphal stage. Longevity was also reduced by adult stress although to a lesser extent, and patterns were not connected to duration. Post-stress productivity decreased following adult and nymphal stress and the decrease tended to be correlated with stress duration. The rate of offspring production was more affected by adult stress than nymphal stress. Productivity and longevity effects, when combined, showed that the largest effect of heat stress occurred at the early nymphal stage. These findings highlight the complex ways in which heat stress at a particular life stage influences later fitness and they also emphasize the importance of considering multiple fitness components when assessing stress effects. © 2019 Society of Chemical Industry.


Expression of sarcoidosis related genes in lung lavage cells.
Sarcoidosis is a systemic granulomatous multiorgan disease of unknown cause. Some facts point to a genetically determined predisposition, like associations with certain Major Histocompatibility Antigens Class I- and II-types (MHC). Mycobacterial DNA has been found in about 30% of sarcoidosis patients within the granulomas, which has been interpreted as a probable trigger mechanism. Cells from bronchoalveolar lavage (BAL) of sarcoidosis patients were stimulated with dead Mycobacterium avium and gene expression was studied after six hours. Gene expression was profiled by hybridization to PCR filters (Human UniGene Set RZPD-1). To avoid the detection of effects related to secondary and tertiary inflammatory messages, we compared gene expression in sarcoidosis with that of tuberculosis and extrinsic allergic alveolitis. After normalization genes up- or downregulated for a factor of at least 1.8 were further analyzed. Genes differentially expressed in sarcoidosis as well as in tuberculosis or EAA, respectively, were subtracted. Four different genes were exclusively upregulated in sarcoidosis: fatty acid binding protein 4 (FABP4), B-MYB, and two EST's. FABP4 has already been described in some autoimmune diseases, but its function in sarcoidosis is unknown. B-MYB is a potent growth factor for haematopoietic cells including lymphocytes. It might be one of the central genes upregulated in sarcoidosis and by that inducing clonal expansion of sarcoidosis-antigen primed T-helper-lymphocytes. Clonal selection of T-helper cells might be facilitated by c-Akt together with Tcl-1, both also upregulated in sarcoidosis. For the two ESTs neither function nor location is known.


Amphotericin B in the therapy of Candida glabrata endophthalmitis after penetrating keratoplasty.
Candida glabrata is a rare cause of endophthalmitis after penetrating keratoplasty. Adequate therapy is still under discussion. With respect to severe complications and side effects of antifungal therapy, a substantial knowledge of sensitivity and resistance of the organism is necessary. We report on a 26-year-old man with a hyperacute onset of the infection only 10 hours after surgery. A combined therapy for fluconazole and steroids administered over 3 months had shown no effect on intraocular infection. After topical and intracameral application of amphotericin B in combination with topical prednisolone 3 months after the onset of the endophthalmitis, the infection disappeared within 14 days, and the graft remained clear for 2 months. No toxic effects were noticed. In the case presented here, topical and intracameral application of amphotericin B was sufficient and safe in the therapy for C. glabrata endophthalmitis after penetrating keratoplasty. Although typically the intraocular infection is first noticed within the first 2 weeks, a hyperacute onset has to be considered.


Improved Integrated Robotic Intraocular Snake.
Retinal surgery can be performed only by surgeons possessing advanced surgical skills because of the small, confined intraocular space, and the restricted free motion of instruments in contact with the sclera. Snake-like robots could be essential for use in retinal surgery to overcome this problem. Such robots can approach from suitable directions and operate delicate tissues when performing retinal vein cannulation, epiretinal membrane peeling and so on. In this study, we propose an improved integrated robotic intraocular snake (I2RIS), which is a new version of our previous IRIS. This update focuses on the dexterous distal unit design and the drive unit design. The proposed dexterous distal unit consists of small elements with reduced contact stress. The proposed drive unit includes a new wire drive mechanism where the drive pulley is mounted at a right angle relative to the actuation direction (also, relative to the conventional direction). A geometric analysis and mechanical design show that the proposed drive mechanism is simpler and easier to assemble and yields higher accuracy than the conventional drive mechanism. Furthermore, considering clinical use, the instrument of the I2RIS is detachable from the motor unit for cleaning, sterilization, and attachment of various surgical tools. Weighing merely 31.3 g, the proposed mechanism is only one third of the weight of the conventional IRIS. The basic functions and effectiveness of the proposed mechanism are verified by experiments on 5:1 scaled-up models of the dexterous distal unit and actual-size models of the instrument and motor units.


Cyclodextrin-Modified inorganic materials for the construction of nanocarriers.
Inorganic nanoparticles, such as gold, silver, quantum dots and magnetic nanoparticles, offer a promising way to develop multifunctional nanoparticles for biomedical applications. Such nanoparticles have the potential to combine in a single, stable construct various functionalities, simultaneously providing imaging abilities, thermal therapies and the ability to deliver drugs in a targeted fashion. An approach for providing drug loading abilities to these inorganic nanoparticles consists in the modification of their surface with a coating of cyclodextrins, and thereby endowing the nanoparticles with the potential of functioning as drug nanocarriers. This review presents the advances carried out in the preparation of cyclodextrin-contained gold, silver, quantum dot and magnetic nanoparticles as well as their applications as drug nanocarriers. The nanoparticle surface can be modified incorporating cyclodextrin moieties, (i) in situ during the synthesis of the nanoparticles, either using the cyclodextrin as reducing agent or as stabilizer; or (ii) in a post-synthetic stage. The cyclodextrin coating contributes to provide biocompatibility to the nanoparticles and to reduce their cytotoxicity. Cyclodextrin-modified nanoparticles display a multivalent presentation of quasi-hydrophobic cavities that enables, not only drug loading in a non-covalent manner, but also the non-covalent assembly of targeting motifs and optical probes. This paper also provides an overview of some of the reported applications including the in vitro studies and, to a lesser extent, in vivo studies on the drug-loaded nanoparticles behavior.


A selective electrocatalyst-based direct methanol fuel cell operated at high concentrations of methanol.
Owing to the serious crossover of methanol from the anode to the cathode through the polymer electrolyte membrane, direct methanol fuel cells (DMFCs) usually use dilute methanol solutions as fuel. However, the use of high-concentration methanol is highly demanded to improve the energy density of a DMFC system. Instead of the conventional strategies (for example, improving the fuel-feed system, membrane development, modification of electrode, and water management), we demonstrate the use of selective electrocatalysts to run a DMFC at high concentrations of methanol. In particular, at an operating temperature of 80°C, the as-fabricated DMFC with core-shell-shell Au@Ag2S@Pt nanocomposites at the anode and core-shell Au@Pd nanoparticles at the cathode produces a maximum power density of 89.7 mW cm-2 at a methanol feed concentration of 10 M and maintains good performance at a methanol concentration of up to 15 M. The high selectivity of the electrocatalysts achieved through structural construction accounts for the successful operation of the DMFC at high concentrations of methanol.


First reported case of intraocular Gnathostoma spinigerum in Cambodia.
A live intraocular nematode was identified from a 37 year-old man presented with iritis, pain, redness, lacrimation, swelling, vision loss and intermittent blindness during many hours per day of the left eye. By using slit lamp examination, a worm was removed from iris in an ophthalmology outpatient department setting and sent to the Medical Microbiology Laboratory, Institut Pasteur du Cambodge. Gnathostoma spinigerum was identified, based on its typical morphology via microscopic examination. Based on our diagnosis, the patient was treated by oral albendazole and responded well to this therapy.


Segmental polymethylmethacrylate-augmented pedicle screw fixation in patients with bone softening caused by osteoporosis and metastatic tumor involvement: a clinical evaluation.
Instrumentation of the osteoporotic spine may result in bone failure because of pedicle screw loosening and pullout. A clinical evaluation of a novel fenestrated bone tap used in pedicle screw augmentation was performed to determine the performance and safety of this technique. Over a 2.5-year period, the clinical and radiographic results of 119 consecutive patients who underwent instrumented arthrodesis were reviewed. Of these patients, 23 had bone softening secondary to osteoporosis and/or metastatic spinal tumor involvement. These patients underwent surgical decompression and spinal instrumentation. Six patients (26%) had metastatic spine disease (squamous cell lung carcinoma, renal cell carcinoma, bladder carcinoma, breast, prostate, and uterine adenocarcinoma); five patients (22%) had a degenerative spondylolisthesis; and 12 patients (52%) had burst fractures, eight as a result of benign causes and four as a result of metastatic disease. Four (17%) patients underwent revision surgery of previous pedicle screw failure resulting from bone softening and pseudarthrosis. A total of 98 levels were fused using 158 polymethylmethacrylate-augmented screws. None of the patients experienced operative death, myocardial infarction, hypoxemia, intraoperative hypotension, radiculopathy, or myelopathy. Asymptomatic anterior cement extravasation was observed in nine patients (39%). There was one asymptomatic polymethylmethacrylate pulmonary embolus and one wound infection. There was no significant relationship between cement extravasation and the quantity used, levels augmented, or location (P > 0.05). There were no construct failures. Polymethylmethacrylate-augmented pedicle screw fixation reduces the likelihood of pedicle screw loosening and pullout in patients with osteoporosis requiring instrumented arthrodesis.


Interaction of imidazolines with alkylation-sensitive and -resistant alpha-1 adrenoceptor subtypes.
The interaction of imidazolines with alpha-1 adrenoceptor subtypes sensitive and resistant to inactivation by SZL-49 and chlorethylclonidine (CEC) has been evaluated. Clonidine, oxymetazoline, phentolamine and naphazoline or the phenethylamine, phenylephrine, interacted with high- and low-affinity sites labeled by [3H]prazosin. SZL-49 (1-1000 nM) eliminated the high-affinity sites and caused a significant reduction of the low-affinity sites. CEC (1-100 microM) reduced the number of low-affinity sites, while the effect on high-affinity sites was dependent on the route of administration. In control aortic rings the dose-response curves for either clonidine or naphazoline were biphasic, consisting of high- and low-affinity components. Only the high-affinity component was blocked by prazosin. SZL-49 was more potent than CEC at inhibiting agonist-induced contraction of rat aortic rings. The agonist responses obtained after treatment with either SZL-49 or CEC were only weakly antagonized by prazosin. The combination of SZL-49 and CEC produced no greater inhibition of muscle contraction than did SZL-49 alone. These data show that 1) imidazolines interact with different affinity at sites labeled by [3H]prazosin and these sites correspond to the alpha-1a and alpha-1b adrenoceptor subtype designation; 2) imidazolines induce smooth muscle contraction by interacting at high- and low-affinity sites; 3) these low-affinity sites do not appear to have properties of an alpha-1 adrenoceptor; 4) there may be three sites of interaction for imidazolines on the aorta, the alpha-1a and alpha-1b adrenoceptors and a site that does not have alpha-1 adrenoceptor characteristics.


The role of UV-B light in skin carcinogenesis through the analysis of p53 mutations in squamous cell carcinomas of hairless mice.
Mutation spectra of the p53 gene from human skin carcinomas have been connected to solar UV radiation. For comparison we have characterized the mutation spectrum of the p53 gene in a very large sample of squamous cell carcinomas from hairless mice induced with UV of wavelength 280-320 nm (UV-B), which have substantiated the mutagenic effects of UV-B radiation in vivo. Tumors from hairless mice, random bred SKH:HR1 as well as inbred SKH:HRA strains, which are analyzed for mutations in the conserved domains of the p53 protein present a very specific mutation spectrum. The observed mutation frequency after chronic UV-B radiation in the p53 gene ranged from 54% (SKH-HRA) to 73% (SKH-HR1) among the 160 tumors analyzed. Over 95% of the mutations were found at dipyrimidine sites located in the non-transcribed strand, the majority were C-->T transitions and 5% were CC-->TT tandem double mutations. Four distinct UV-B mutation hot spots have been identified for the first time: two major ones at codons 267 (33%) and 272 (19%) and two minor ones at codons 146 (10%) and 173 (4%). The codon 267 hot spot consists of a CpG preceded by a pyrimidine, which confirms in vivo an important role for this UV-B mutable site in UV-B-induced skin tumors that is not found in other types of mouse tumors. Comparison with mutation spectra from human skin carcinomas fully validates the merits of the hairless mouse model for studying the molecular mechanisms of skin carcinogenesis. For example, the murine hot spot at codon 272 does have a full equivalent in human skin carcinomas. In contrast, the human equivalent of the murine codon 267 lacks the dipyrimidine site and therefore fails to be a pronounced hot spot in human skin carcinomas; however, this site is one of the major hot spots in human internal cancers (evidently not induced by UV radiation but probably by deamination of the 5 methyl cytosine).


Innovative approaches to regenerate enamel and dentin.
The process of tooth mineralization and the role of molecular control of cellular behavior during embryonic tooth development have attracted much attention the last few years. The knowledge gained from the research in these fields has improved the general understanding about the formation of dental tissues and the entire tooth and set the basis for teeth regeneration. Tissue engineering using scaffold and cell aggregate methods has been considered to produce bioengineered dental tissues, while dental stem/progenitor cells, which can differentiate into dental cell lineages, have been also introduced into the field of tooth mineralization and regeneration. Some of the main strategies for making enamel, dentin, and complex tooth-like structures are presented in this paper. However, there are still significant barriers that obstruct such strategies to move into the regular clinic practice, and these should be overcome in order to have the regenerative dentistry as the important mean that can treat the consequences of tooth-related diseases.


Analysis of an influenza A virus mutant with a deletion in the NS segment.
The influenza virus host range mutant CR43-3, derived by recombination from the A/Alaska/6/77 and the cold-adapted and temperature-sensitive A/Ann Arbor/6/60 viruses, has previously been shown to possess a defect in the NS gene. To characterize this defect, nucleotide sequence data were obtained from cloned cDNAs. The CR43-3 NS gene was found to be 854 nucleotides long and to derive from the NS gene of the A/Alaska/6/77 parent virus by an internal deletion of 36 nucleotides. Direct sequencing of RNA 8 of CR43-3 virus confirmed that the deletion in the NS1-coding region was not an artifact that was generated during the cloning procedure. Protein analysis indicated that the NS1 protein of CR43-3 virus was synthesized in equal amounts in the restrictive (MDCK) cells as well as in the permissive (PCK) host cells. Also, indirect immunofluorescence studies of virus-infected cells showed that the NS1 protein of CR43-3 virus, like that of the parent viruses, accumulates in the nuclei of both cell systems. Although no differences in synthesis or localization of the NS1 protein could be detected, a consistent reduction in M1 protein was noted in CR43-3 virus-infected, nonpermissive cells as compared with that of the permissive host. Since analysis of the CR43-3 virus required us to obtain the NS nucleotide sequence of the 1977 isolate A/Alaska/6/77, we were able to compare this sequence with those of corresponding genes of earlier strains. The result of this analysis supports the idea of a common lineage of human influenza A viruses isolated over a 43-year period.


The mediating role of state anger in the associations between intentions to participate in the criminal trial and psychopathology in traumatically bereaved people.
Victims of crimes have been granted increasing procedural rights to participate in the juridical process since the mid 1990s. However, knowledge about the (anti)-therapeutic effect of participation is limited. We examined the associations between symptom levels of persistent complex bereavement disorder (PCBD), posttraumatic stress disorder (PTSD), and depression and the intention to participate in a criminal trial. Furthermore, we investigated the mediating role of state anger in these associations. People who lost loved ones after a plane disaster with flight MH17 (N = 203) completed questionnaires within three weeks before the start of the criminal trial. Mediation analyses indicated that people, who did not intend to actively participate in the trial by delivering a written or oral victim statement, were less likely to experience anger, which is, in turn, associated with attenuated psychopathology levels. State anger explains 68% of the effect of the intention to exercise the right to speak on PCBD levels. An important limitation is the cross-sectional study design, which precludes conclusions about temporal associations. More research is needed to improve preparation and support of bereaved people when they intend to exercise their victim rights during a criminal trial.


Surface engineering of nanoporous substrate for solid oxide fuel cells with atomic layer-deposited electrolyte.
Solid oxide fuel cells with atomic layer-deposited thin film electrolytes supported on anodic aluminum oxide (AAO) are electrochemically characterized with varying thickness of bottom electrode catalyst (BEC); BECs which are 0.5 and 4 times thicker than the size of AAO pores are tested. The thicker BEC ensures far more active mass transport on the BEC side and resultantly the thicker BEC cell generates ≈11 times higher peak power density than the thinner BEC cell at 500 °C.


In vivo incorporation of unnatural amino acids to probe structure, dynamics, and ligand binding in a large protein by nuclear magnetic resonance spectroscopy.
In vivo incorporation of isotopically labeled unnatural amino acids into large proteins drastically reduces the complexity of nuclear magnetic resonance (NMR) spectra. Incorporation is accomplished by coexpressing an orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for the unnatural amino acid added to the media and the protein of interest with a TAG amber codon at the desired incorporation site. To demonstrate the utility of this approach for NMR studies, 2-amino-3-(4-(trifluoromethoxy)phenyl)propanoic acid (OCF 3Phe), (13)C/(15)N-labeled p-methoxyphenylalanine (OMePhe), and (15)N-labeled o-nitrobenzyl-tyrosine (oNBTyr) were incorporated individually into 11 positions around the active site of the 33 kDa thioesterase domain of human fatty acid synthase (FAS-TE). In the process, a novel tRNA synthetase was evolved for OCF 3Phe. Incorporation efficiencies and FAS-TE yields were improved by including an inducible copy of the respective aminoacyl-tRNA synthetase gene on each incorporation plasmid. Using only between 8 and 25 mg of unnatural amino acid, typically 2 mg of FAS-TE, sufficient for one 0.1 mM NMR sample, were produced from 50 mL of Escherichia coli culture grown in rich media. Singly labeled protein samples were then used to study the binding of a tool compound. Chemical shift changes in (1)H-(15)N HSQC, (1)H-(13)C HSQC, and (19)F NMR spectra of the different single site mutants consistently identified the binding site and the effect of ligand binding on conformational exchange of some of the residues. OMePhe or OCF 3Phe mutants of an active site tyrosine inhibited binding; incorporating (15)N-Tyr at this site through UV-cleavage of the nitrobenzyl-photocage from oNBTyr re-established binding. These data suggest not only robust methods for using unnatural amino acids to study large proteins by NMR but also establish a new avenue for the site-specific labeling of proteins at individual residues without altering the protein sequence, a feat that can currently not be accomplished with any other method.


Long-term survival of adult human lung growing subcutaneously in congenitally athymic nude mice.
Small airways and alveoli from normal adult human lung were implanted subcutaneously in nude mice. When the tissue was removed at 16 months the airway had formed into fluid-filled epithelium-lined cysts. The epithelial lining was typical of small and terminal airways, except where intracystic pressure had apparently flattened the epithelium. Ultrastructural examination of the columnar ciliated cells revealed supranuclear accumulations of granules, some irregular in outline and others lamellated. The nonciliated secretory cells closely resembled serous cells. The alveoli survived less well. Although partly expanded by secretion, probably from the type II pneumonocytes, the walls were frequently thickened by an increase in connective tissue, and there were few capillaries. The cells for which there was positive identification, or good presumptive evidence, for being of human type were columnar ciliated cells, serous cells, smooth muscle, cartilage, mast cells, type II pneumonocytes, and basal epithelial cells; the latter two cell types were apparently proliferating. The results show that human airway can be maintained long term as a xenograft.


Atomic-layered V2C MXene containing bismuth elements: 2D/0D and 2D/2D nanoarchitectonics for hydrogen evolution and nitrogen reduction reaction.
The exploitation of two-dimensional (2D) vanadium carbide (V2CTx, denoted as V2C) in electrocatalytic hydrogen evolution reaction (HER) and nitrogen reduction reaction (NRR) is still in the stage of theoretical study with limited experimental exploration. Here, we present the experimental studies of V2C MXene-based materials containing two different bismuth compounds to confirm the possibility of using V2C as a potential electrocatalyst for HER and NRR. In this context, for the first time, we employed two different methods to synthesize 2D/0D and 2D/2D nanostructures. The 2D/2D V2C/BVO consisted of BiVO4 (denoted BVO) nanosheets wrapped in layers of V2C which were synthesized by a facile hydrothermal method, whereas the 2D/0D V2C/Bi consisted of spherical particles of Bi (Bi NPs) anchored on V2C MXenes using the solid-state annealing method. The resultant V2C/BVO catalyst was proven to be beneficial for HER in 0.5 M H2SO4 compared to pristine V2C. We demonstrated that the 2D/2D V2C/BVO structure can favor the higher specific surface area, exposure of more accessible catalytic active sites, and promote electron transfer which can be responsible for optimizing the HER activity. Moreover, V2C/BVO has superior stability in an acidic environment. Whilst we observed that the 2D/0D V2C/Bi could be highly efficient for electrocatalytic NRR purposes. Our results show that the ammonia (NH3) production and faradaic efficiency (FE) of V2C/Bi can reach 88.6 μg h-1 cm-2 and 8% at -0.5 V vs. RHE, respectively. Also V2C/Bi exhibited excellent long-term stability. These achievements present a high performance in terms of the highest generated NH3 compared to recent investigations of MXenes-based electrocatalysts. Such excellent NRR of V2C/Bi activity can be attributed to the effective suppression of HER which is the main competitive reaction of the NRR.


Penile hygiene: puberty, paraphimosis and personal care for men and boys with an intellectual disability.
Supporting men and boys with an intellectual disability (ID) to meet their penile hygiene needs is perhaps one of the least acknowledged but most confronting issues facing care staff. The delivery of intimate hygiene can be a challenging topic particularly as it has been drawn into the emerging sexuality discourse and the ongoing abuse narrative. Compounding this challenge is the lack of guidance in intimate care for support staff. In addition, whereas the male with an ID outnumber the female, female care staff greatly outnumber male staff. Whether this situation affects outcomes for men and boys with an ID is unknown but it is an issue which should be examined. This paper reports data from two separate studies, one quantitative the other qualitative, which sought to explore penile hygiene as a male health issue. Results show the practice of care staff to be inconsistent, the views and values of care staff to be divergent. Some patterns and contextual differences were identified depending upon the gender of care staff. An emerging dialogue described some of the positive contributions that male staff make to men and boys with an ID. The penile health needs of men and boys with an ID are being compromised by a lack of guidance, training, knowledge and limited gender-sensitive care.


The wall eclipsing sign on pulmonary artery computed tomography angiography is pathognomonic for pulmonary artery sarcoma.
The objective of this study was to evaluate the imaging characteristics of pulmonary artery sarcoma (PAS) on pulmonary artery computed tomography angiography (PACTA) that can be used to differentiate between PAS and pulmonary thromboembolic diseases, including chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE). The clinical data and imaging characteristics of 12 patients with PAS, 156 patients with CTEPH, and 426 patients with APE who were treated at Beijing Anzhen Hospital from January 2007 to August 2013 were retrospectively analyzed. All patients underwent PACTA before treatment, and the diagnoses of PAS and CTEPH were all confirmed by surgical biopsy. All 12 PAS patients were initially misdiagnosed and received inappropriate thrombolytic and/or anticoagulant therapy before they were referred for surgical intervention. The mean time from PACTA to surgical intervention was 5.5±3.7 months (range 2-11 months). On PACTA, the PAS lesion always eclipsed the wall of the pulmonary artery before infiltrating outside the pulmonary artery, which was termed the wall eclipsing sign. This sign was observed in all PAS patients but was not observed in any CTEPH or APE patients. PAS is a rare neoplasm with a poor prognosis, and is easily misdiagnosed as thromboembolic disease. The wall eclipsing sign on PACTA is pathognomonic for PAS, and patients with this sign should be investigated to confirm the diagnosis and should undergo surgical intervention as soon as possible, rather than receiving thrombolytic or anticoagulant therapy.


Per-sextant localization and staging of prostate cancer: correlation of imaging findings with whole-mount step section histopathology.
The objective of our study was to determine the diagnostic accuracy and interobserver agreement of 1.5-T prostatic MRI for per-sextant tumor localization and staging of prostate cancer as compared with whole-mount step section histopathology. Combined endorectal-pelvic phased-array prostatic MRI scans obtained at 1.5 T of 106 patients with biopsy-proven prostate cancer who had undergone radical prostatectomy with whole-mount step section histopathology within 28 days of MRI were retrospectively analyzed by three independent abdominal radiologists (reviewers 1, 2, and 3). Sextants of the prostate (right and left base, middle, and apex) were evaluated for the presence of prostate cancer and extracapsular extension (ECE) using a 5-point confidence scale. Data were statistically analyzed using receiver operating characteristic (ROC) analysis. Interobserver variability was assessed by kappa statistics. For calculation of sensitivity and specificity, data from the 5-point confidence scale were dichotomized into negative (score of 1-3) or positive (score of 4 or 5) findings. Forty-one patients had ECE (tumor stage T3), and 65 patients had organ-confined disease (stage T2). Of 636 prostatic sextants, 417 were positive for prostate cancer and 135 were positive for ECE at histopathology. For prostate cancer localization, ROC analysis yielded area under the ROC curve (AUC) values ranging from 0.776 +/- 0.023 (SD) to 0.832 +/- 0.027. For the detection of ECE, the AUC values ranged from 0.740 +/- 0.054 to 0.812 +/- 0.045. Interobserver agreement (kappa) ranged from 0.49 to 0.60 for prostate cancer localization and from 0.59 to 0.67 for the detection of ECE. Using the sextant framework, independent observers reach similar accuracy with moderate to substantial agreement for the localization of prostate cancer and ECE by means of MRI of the prostate.


Unruptured intracranial aneurysms: an assessment of the annual risk of rupture based on epidemiological and clinical data.
From autopsy and neuroradiological studies a maximum prevalence of unruptured intracranial aneurysms (UA) of 0.5% in the general population is revealed. Studies concerning the incidence of aneurysmal subarachnoid haemorrhage (SAH) revealed 10 cases per 100,000 inhabitants per year. From these epidemiological parameters a minimum annual risk of 2% of rupture of an UA is calculated. It is in accordance with clinical studies, which also demonstrated an annual risk of UA rupture of at least 2%. No critical size of the UA predisposing to rupture has been found. Operation on diagnosed UA is recommended because of the serious prognosis after aneurysmal SAH (morbidity 20%-25% and mortality 50%-60%) and because the morbidity (4%) and the mortality (0%) after operative treatment of UA are very low.


Bulbous splenic vein as a cause of renal pseudotumor.
A number renal and suprarenal pseudotumors have been described during the past two decades, paralleling the development of selective visceral angiography. An apparent left upper pole renal mass in a 71-year-old hypertensive man was found to ba a bulbous portion of the splenic vein during angiography. The anatomical basis of this renal pseudotumor is discussed.


High-resolution satellite-based analysis of ground-level PM2.5 for the city of Montreal.
Satellite remote sensing offers the opportunity to determine the spatial distribution of aerosol properties and could fill the gap of ground-level observations. Various algorithms have recently been developed in order to retrieve the aerosol optical depth (AOD) at continental scales. However, they are, to some extent, subject to coarse spatial resolutions which are not appropriate for intraurban scales as usually needed in health studies. This paper presents an improved AOD retrieval algorithm for satellite instrument MODIS at 1-km resolution for intraurban scales. The MODIS-retrieved AODs are used to derive the ground-level PM2.5 concentrations using the aerosol vertical profiles and local scale factors obtained from the GEOS-Chem model simulation. The developed method has been applied to retrieve the AODs and to evaluate the ground-level PM2.5 over the city of Montreal, Canada for 2009 on daily, monthly and annual scales. The daily and monthly results are compared with the monitoring values with correlations R(2) ranging from 0.86 to 0.93. Especially, the annual mean PM2.5 concentrations are in good agreement with the measurement values at all monitoring stations (r=0.96, slope=1.0132 ± 0.0025, intercept=0.5739 ± 0.0013). This illustrates that the developed AOD retrieval algorithm can be used to retrieve AODs at a higher spatial resolution than previous studies to further derive the regional full coverage PM2.5 results at finer spatial and temporal scales. The study results are useful in health risk assessment across this region.


[Current flora of mandibular osteomyelitis].
1) Blood-borne osteomyelitis may have a dental portal of entry. This results in a bacteraemia or septicaemia due to organisms other than staphylococci. In such cases, osseous lesions occur at a distance from the initial dental site. 2) As far as antibiotic treatment is concerned:--It must be begun early but not prematurely, i.e. bacteriological studies should be undertaken before antibotic therapy is started, possibly to be later changed in the light of laboratory results.--It should be combined, with a preference for two antibiotics which result in a bactericidal combination, as soon as the responsible organism is identified.--It should be given in high dosage, in view of the problem of diffusion of the antibiotic to the centre of the necrotic bone lesion.--It should be prolonged, based upon clinical, laboratory and radiological findings.


Urinary amino acid excretion in acute leukemia.
Urinary amino acid excretion was determined in 31 leukemic patients and 29 normal individuals by rapid gas chromatographic analysis of 16 amino acids as their N-acetyl-n-propyl esters. The leukemic patients were concurrently undergoing, or had recently completed, chemotherapy. It was found that aspartic acid, threonine, and serine were of significance in distinguishing between patients "on" therapy and those "off" therapy. Patients with advanced disease have the greatest aminoaciduria, although both the normal and leukemic populations have wide individual ranges. Within both populations, men excrete a greater variety and quantity of amino acids than women. It is concluded that analysis of urinary amino acids represents a history of complex metabolic events, which is potentially useful for evaluating patient response to chemotherapy in leukemia.


Cyclooxygenase-2 positively regulates Akt signalling and enhances survival of erythroleukemia cells exposed to anticancer agents.
Cyclooxygenase-2 (COX-2) has been found to be highly expressed in many types of cancers and to contribute to tumorigenesis via the inhibition of apoptosis, increased angiogenesis and invasiveness. In hematological malignancies, COX-2 expression was found to correlate with poor patient prognosis. However, the exact role of COX-2 expression in these malignancies, and particularly in erythroleukemias, remains unclear. The aim of this work was to describe and understand the relationships between COX-2 expression and apoptosis rate in erythroleukemia cells after apoptosis induction by several anticancer agents. We used three different erythroleukemia cell lines in which COX-2 expression was modulated by transfection with either COX-2 siRNA or COX-2 cDNA. These cellular models were then treated with apoptosis inducers and apoptosis onset and intensity was followed. Cell signalling was evaluated in unstimulated transfected cells or after apoptosis induction. We found that COX-2 inhibition rendered erythroleukemia cells more sensitive to apoptosis induction and that in cells overexpressing COX-2 apoptosis induction was reduced. We demonstrated that COX-2 inhibition decreased the pro-survival Akt signalling and activated the negative regulator of Akt signalling, phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Conversely, in COX-2 overexpressing cells, Akt signalling was activated and PTEN was inhibited. In these last cells, inhibition of casein kinase 2 or Akt signalling restored sensitivity to apoptotic agents. Our findings highlighted that COX-2 can positively regulate Akt signalling mostly through PTEN inhibition, partly via casein kinase 2 activation, and enhances survival of erythroleukemia cells exposed to anticancer agents.


Cross-sectional association between oral health and retinal microcirculation.
To investigate the relation between oral health status and microcirculation, we analysed the association between periodontitis and number of teeth with retinal vessel diameters in a population-based study. We analysed data from the Study of Health in Pomerania-TREND (SHIP-TREND). All subjects (3,183 for number of teeth, 3,013 for mean probing depth and 2,894 for mean attachment level) underwent nonmydriatic funduscopy and dental examination. We measured central retinal arteriolar (CRAE), venular (CRVE) vessel diameters and calculated arterio-venous ratio (AVR) from static vessel analysis (SVA). Periodontal status was assessed using the case definition of the Center for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP). Data were analysed by linear (CRAE, CRVE, AVR) and logistic regression (AVR < 0.8) adjusted for age, sex, smoking status, alcohol consumption, body mass index, systolic blood pressure, hsCRP and type-2-diabetes mellitus. Only in men, significant associations were found between periodontal and retinal conditions. Severe periodontitis [β = -0.0120 (-0.0218; -0.0007 95%-CI)] and mean probing depth [β = -0.0054 (-0.0105; -0.0002 95%-CI)] were inversely associated with AVR; severe periodontitis [β = 3.80 (0.61; 6.98 95%-CI)], mean probing depth [β = 1.86 (0.23; 3.49 95%-CI)] and mean attachment level [β = 1.31 (0.34; 2.27 95%-CI)] with CRVE and mean attachment level with CRAE [β = 0.91 (0.14; 1.69 95%-CI)]. Our results point towards an association between periodontal conditions and AVR in men. Periodontitis may impact microvascular endothelium function. Improving oral health to reduce periodontitis might lead to reduced risk for other age-related diseases.


The polar profile of ancient proteins: a computational extrapolation from prebiotics to paleobiochemistry.
This paper addresses the polar profile of ancient proteins using a comparative study of amino acids found in 25 000 000-year-old shells described in Abelson's work. We simulated the polar profile with a computer platform that represented an evolutionary computational toy model that mimicked the generation of small proteins starting from a pool of monomeric amino acids and that included several dynamic properties, such as self-replication and fragmentation-recombination of the proteins. The simulations were taken up to 15 generations and produced a considerable number of proteins of 25 amino acids in length. The computational model included the amino acids found in the ancient shells, the thermal degradation factor, and the relative abundance of the amino acids observed in the Miller-Urey experimental simulation of the prebiotic amino acid formation. We found that the amino acid polar profiles of the ancient shells and those simulated and extrapolated from the Miller-Urey abundances are coincident.


Disease prevention and anti-vector campaigns: insects.
Control of insect vector populations is an integral part of disease management but has many challenges. Area-wide campaigns, mainly based on insecticide administration, are most effective for control of insect populations, whereas disease prevention is more localised and protects a smaller number of animals against insect vector contact. Various control and prevention techniques are available for use against most insectvectors and are illustrated here by focusing on two important insect groups: biting midges and tsetse flies. Biting midges (Culicoides) present a major threat and challenge to disease and vector control because of limited large-scale control options and the huge population sizes and wide distribution of these insects. Localised disease prevention forms the basis for control, and there is a need for better understanding of the ecology and biology of these insects in order to develop large-scale control techniques. The necessary techniques to effectively control tsetse flies (Glossina) and trypanosomosis exist for both localised and area-wide control. The development of a new, cost-efficient device has had a significant impact in the control of both human and animal trypanosomosis. This is especially relevant in Uganda, where the movement of livestock for trading purposes is implicated in disease distribution and poses an immediate health threat where the two forms of the disease overlap. Although many successes have been achieved, continued research and development is needed to keep abreast of the multitude of challenges in insect vector control.


Lack of antifertility properties of novel halogenated glycolytic inhibitors and the urinary excretion and metabolism of 1,6-dichloro-1,6-dideoxy-D-fructofuranose in the male rat.
The antifertility action of (R,S)-alpha-chlorohydrin administered orally to male rats was compared with that of several novel chlorinated compounds known to inhibit glycolysis and the kinematics of rat sperm in vitro. Oral gavage of 1,6-dichloro-1,6-dideoxy-D-fructofuranose (dichlorodideoxyfructose, DCF), 1-chloro-3-hydroxypropanone, its dimethylketal and bromopyruvate did not reduce the fertility of male rats below that of controls at the equivalent antifertility dose of (R,S)-alpha-chlorohydrin (5 mg/kg/day) or higher. As anticipated for a compound cleaved to products of (S)-chirality even high doses of DCF (200 mg/kg) showed no effect on renal function. 36Cl-Labelled DCF administered orally to male rats was eliminated only slowly in the urine (16% of the ingested dose excreted in 96 h). In the first 8 h, approximately 50% of DCF was excreted unchanged, 30% was excreted as 3-chlorolactate (BCLA), the oxidation product 3-chlorolactaldehyde and 25% as Cl-. By 24 h little DCF remained and the major metabolite (70%) was BCLA and 20% Cl-. The high rate of dechlorination is most likely responsible for the low antifertility action of DCF.


Characterization of resistance to selected antibiotics and Panton-Valentine leukocidin-positive Staphylococcus aureus in a healthy student population at a Malaysian University.
This study aims to assess the antimicrobial susceptibility profiles of Staphylococcus aureus strains isolated from university students and to determine the prevalence of constitutive and inducible clindamycin resistance, the latter being able to cause therapeutic failure due to false in vitro clindamycin susceptibility. S. aureus strains were isolated from the nasal swabs of 200 health sciences students of a Malaysian university. Twelve classes of antibiotics were used to evaluate the antimicrobial susceptibility profiles with the macrolide-lincosamide-streptogramin B (MLSB) phenotype for inducible clindamycin resistance determined by the double-diffusion test (D-test). Carriage of resistance and virulence genes was performed by PCR on S. aureus isolates that were methicillin resistant, erythromycin resistant and/or positive for the leukocidin gene, pvl (n=15). Forty-nine isolates were viable and identified as S. aureus with four of the isolates characterized as methicillin-resistant S. aureus (MRSA; 2.0%). All isolates were susceptible to the antibiotics tested except for penicillin (resistance rate of 49%), erythromycin (16%), oxacillin (8%), cefoxitin (8%) and clindamycin (4%). Of the eight erythromycin-resistant isolates, iMLSB was identified in five isolates (three of which were also MRSA). The majority of the erythromycin-resistant isolates harbored the msrA gene (four iMLSB) with the remaining iMLSB isolate harboring the ermC gene. The presence of MRSA isolates which are also iMLSB in healthy individuals suggests that nasal carriage may play a role as a potential reservoir for the transmission of these pathogens.


Thermal C-H borylation using a CO-free iron boryl complex.
New CO-free iron boryl complexes, CpFe(PR3)2(Bpin), are described. The CpFe(PEt3)2(Bpin) derivative is uniquely capable of UV-free arene borylation at 70 °C via a dissociative pathway. Catalytic C-H borylation does not proceed using either monometallic or heterobimetallic schemes, and this failure is rationalized through analysis of relative pKa values for the corresponding iron hydride species.


Selective immunosuppression of prodigiosin 25-C and FK506 in the murine immune system.
The immunosuppressive effects of prodigiosin 25-C were studied in comparison with FK506. Both prodigiosin 25-C and FK506 suppressed T cell proliferation in response to concanavalin A (con A) or phytohemagglutinin (PHA) more significantly than that to lipopolysaccharide. However, prodigiosin 25-C inhibited con A-mediated mitogenic response more strongly than PHA-mediated one. FK506 showed no selectivity among those responses. In addition, when higher concentration of con A was used an inhibitory effect of prodigiosin 25-C became more evident whereas that of FK506 became less evident. Furthermore, prodigiosin 25-C affected neither interleukin-2 (IL-2) production nor IL-2 receptor (IL-2R) and transferrin receptor (TF-R) expression in vitro, though FK506 extensively inhibited IL-2 production and significantly suppressed IL-2R and TF-R expression. When comparing the effects of prodigiosin 25-C and FK506 in vivo by injecting antigens of different nature to a mouse, prodigiosin 25-C selectively inhibited cytotoxic T lymphocyte (CTL) activity induced by an allogenic mastocytoma, P815, without affecting production of antibody against a thymus dependent (TD) antigen, sheep red blood cell (SRBC). On the contrary, FK506 significantly inhibited both CTL induction and the antibody production. When Brucella abortus, a thymus independent (TI) antigen, and SRBC were simultaneously challenged to a mouse, neither prodigiosin 25-C nor FK506 affected antibody production against the TI antigen while the effect on the TD antigen were the same as described above. The present results revealed the unique immunosuppressive property of prodigiosin 25-C which was different from that of FK506.


Quantitative Proteomic Approach Identifies Vpr Binding Protein as Novel Host Factor Supporting Influenza A Virus Infections in Human Cells.
Influenza A virus (IAV) infections are a major cause for respiratory disease in humans, which affects all age groups and contributes substantially to global morbidity and mortality. IAV have a large natural host reservoir in avian species. However, many avian IAV strains lack adaptation to other hosts and hardly propagate in humans. While seasonal or pandemic IAV strains replicate efficiently in permissive human cells, many avian IAV cause abortive nonproductive infections in these hosts despite successful cell entry. However, the precise reasons for these differential outcomes are poorly defined. We hypothesized that the distinct course of an IAV infection with a given virus strain is determined by the differential interplay between specific host and viral factors. By using Spike-in SILAC mass spectrometry-based quantitative proteomics we characterized sets of cellular factors whose abundance is specifically up- or downregulated in the course of permissive versus nonpermissive IAV infection, respectively. This approach allowed for the definition and quantitative comparison of about 3500 proteins in human lung epithelial cells in response to seasonal or low-pathogenic avian H3N2 IAV. Many identified proteins were similarly regulated by both virus strains, but also 16 candidates with distinct changes in permissive versus nonpermissive infection were found. RNAi-mediated knockdown of these differentially regulated host factors identified Vpr binding protein (VprBP) as proviral host factor because its downregulation inhibited efficient propagation of seasonal IAV whereas overexpression increased viral replication of both seasonal and avian IAV. These results not only show that there are similar differences in the overall changes during permissive and nonpermissive influenza virus infections, but also provide a basis to evaluate VprBP as novel anti-IAV drug target.


Application of condition-based maintenance in health care: A concept analysis.
Chronic illness burdens individuals, organizations and society, costing the US $3.5 trillion annually. Transposed from the engineering industry, condition-based maintenance is a novel concept that holds great promise for alleviating this burden by enhancing current health care delivery methods. Aims of this concept analysis include, (a) develop an operational definition for the term condition-based maintenance and (b) discuss the applicability and effectiveness of condition-based maintenance as applied to health care. A search of engineering and health care literature was completed. The search term "condition-based maintenance" was entered into the PubMed, Wiley Interscience Journals, CINAHL, Journals@Ovid, ProQuest Nursing & Allied Health Source, and Emerald databases. A review of the literature was completed to identify the qualities of condition-based maintenance. Utilizing the Walker and Avant method, antecedents, characteristics, and consequences were identified. A conceptual model of condition-based maintenance was developed encompassing two antecedents, four characteristics, and three consequences. Furthermore, a theoretical definition of condition-based maintenance was derived. Focus on the positive effects of proactively monitoring symptoms among chronically-ill persons is needed. Condition-based maintenance advances the National Institute of Nursing Research's focus on symptom science through the development of personalized strategies to treat and prevent the adverse symptoms of illness.


[The etiopathogenesis of uveitis].
A review of the different etiopathological classification of uveitis is presented. In our present stage of knowledge an exhaustive classification is almost impossible. This is due to the fact that any microorganism foreign body or pathological process which can produce a general inflammation is able to cause an uveitis.


Quantitative magnetic resonance imaging of the upper trapezius muscles - assessment of myofascial trigger points in patients with migraine.
Research in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping. Ten subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs. The trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side. Our approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.


Multiple glioblastomas: Are they different from their solitary counterparts?
Multiple glioblastomas (GBMs) have a reported incidence of 2-20%. We intend to study these subsets of GBMs to know whether these are similar to their solitary counterparts. A retrospective study. We analyzed 7 cases of biopsy-proven multiple GBMs. Multiple GBMs were described if there were >1 lesion which was at least 1 cm apart. The clinical data, radiological features, histopathological and immunohistochemical analysis and follow-up were recorded. The mean age was 45 years (range 17-69 years). All cases presented with features of raised intracranial pressure (ICP). Totally, 3 cases presented with hemiparesis and 2 cases with altered sensorium and generalized tonic clonic seizures each. The median Karnofsky performance status (KPS) was 50. Mean duration of symptoms was 40 days. All lesions were contrast enhancing (2 with homogenous enhancement and 5 had ring enhancement). Total excision of the lesion causing mass effect was done in all cases. Histopathologically, small cells were significantly present in 4 cases, and satellitosis was seen in 5 cases. Glial fibrillary acidic protein (GFAP) was absent in all cases in which small cells were significant. In these 4 cases, the proliferation index ranged from 40% to 95%. Totally, 3 patients died within 2 months of surgery, whereas remaining 4 patients underwent chemo-radiotherapy. We conclude that the cases usually present with features of raised ICP and poor KPS. Histopathologically these lesions show significant small cell population, satellitosis, and GFAP negativity.


CD81 down-regulation on B cells is associated with the response to interferon-alpha-based treatment for chronic hepatitis C virus infection.
The lymphocytic CD81 molecule, capable of modulating type-1/-2 T-helper responses and serving as a putative receptor for hepatitis C virus (HCV), might influence the outcome of anti-HCV treatment. This study characterized the interferon-alpha-induced alteration of lymphocytic CD81. The CD81 levels in healthy subjects and naïve chronic HCV patients were compared, with the results showing that the two groups had comparable surface CD81 levels for total peripheral blood lymphocytes, subpopulation-B, -T, and -NK cells. In vitro interferon-alpha treatment could suppress the CD81 expression from both groups. Subsequently, we compared the in vitro interferon-alpha modulatory effects on lymphocytic CD81 from patients having received anti-HCV therapy with either sustained virological response (SVR) or without SVR. There was a significant down-regulation of the B-cell's CD81 only in the SVR group. The CD81 modulation was further investigated using Daudi lymphoid cell line, showing declined surface CD81 levels following treatment with interferon-alpha, interferon-beta or polyI:C. Thus, interferons could directly decrease CD81 expression. The interferon-alpha effect could be restored by 2-aminopurine, suggesting that double-stranded RNA activated kinase might be involved in the suppression of CD81. In conclusion, CD81 down-regulation is a primary host response to interferon-alpha-based therapy and an immunophenotype associated with anti-HCV SVR.


The advantages of being locked. Assessing the cleavage of short and long RNAs by locked nucleic acid-containing 8-17 deoxyribozymes.
RNA-cleaving deoxyribozymes can be used for the sequence-specific knockdown of mRNAs. It was previously shown that activity of these deoxyribozymes is enhanced when their substrate-binding arms include some locked nucleic acid (LNA) residues, but the mechanistic basis of this enhancement was not explored. Here we dissected the kinetics and thermodynamics underlying the reaction of LNA-containing 8-17 deoxyribozymes. Four 8-17 constructs were designed to target sequences within the E6 mRNA from human papillomavirus type 16. When one of these deoxyribozymes (DNAzymes) and the corresponding LNA-armed enzyme (LNAzyme) were tested against a minimal RNA substrate, they showed similar rates of substrate binding and similar rates of intramolecular cleavage, but the LNAzyme released its substrate more slowly. The superior thermodynamic stability of the LNAzyme-substrate complex led to improved performances in reactions carried out at low catalyst concentrations. The four DNAzymes and the corresponding LNAzymes were then tested against extended E6 transcripts (>500 nucleotides long). With these structured substrates, the LNAzymes retained full activity, whereas the DNAzymes cleaved extremely poorly, unless they were allowed to pre-anneal to their targets. These results imply that LNAzymes can easily overcome the kinetic barrier represented by local RNA structure and bind to folded targets with a faster association rate as compared with DNAzymes. Such faster annealing to structured targets can be explained by a model whereby LNA monomers favor the initial hybridization to short stretches of unpaired residues ("nucleation"), which precedes disruption of the local mRNA structure and completion of the binding process.


Free Triiodothyronine Concentrations are Inversely Associated with Elevated Carotid Intima-Media Thickness in Middle-Aged and Elderly Chinese Population.
Increased carotid artery intima media thickness (C-IMT) is an early feature of atherosclerosis. It has been reported to be altered in patients with thyroid dysfunction, and the evidence is still controversial. The present study aimed to explore the relationship between C-IMT and possible variations in thyroid function in Chinese adults aged 40 years and above. A community-based cross-sectional study was conducted among 2276 non-diabetic participants. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were determined by chemiluminescent microparticle immunoassay. The prevalence of elevated C-IMT decreased according to FT3 quartiles (29.8%, 24.3%, 24.2%, and 22.2%, P for trend=0.005). In both univariate and multivariate linear regression analyses, FT3 levels were inversely associated with C-IMT (both P values ≤ 0.002). Multivariate-adjusted logistic regression analysis showed that high FT3 levels were associated with low prevalent elevated C-IMT. The adjusted odds ratio for elevated C-IMT was 0.71 (95% confidence interval, 0.52-0.99, P=0.04) when comparing the highest with the lowest quartile of FT3. Serum FT3 levels were inversely associated with elevated C-IMT in middle-aged and elderly Chinese adults without diabetes, independent of traditional risk factors for atherosclerosis.


I-A mutation resulted in a selective loss of an antigen-specific Ir gene function.
The immune responses to several antigens were compared in the I-A mutant mouse strain B6.C-H-2bm12 and the wild-type strain C57BL/6. With a lymph node cell proliferation assay, the response to two of these antigens, beef insulin and (TG)A-L, was demonstrated to be controlled by a gene in the I-Ab region. B6.C-H-2bm12 mice failed to respond to beef insulin, while their responses to (TG)A-L, DNP-OVA and PPD were comparable with those of the wild-type strain C57BL/6. Taken together with previous studies, these data suggest that the product of a single pleiotropic I-A gene, an Ia molecule, functions as a histocompatibility, Ia, and MLR antigen, as well as a necessary component for Ir gene function. Furthermore, the data reported here demonstrate that Ia molecules have multiple functional "Ir determinants," one of which has been altered in the B6.C-H-2bm12 mutant. The B6.C-H-2bm12 mice, therefore, represent a powerful analytical tool for the understanding of the cellular and molecular basis for Ir gene control of the immune response.


Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies.
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22) gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.