Changes in inflammatory plasma proteins from patients with chronic pain associated with treatment in an interdisciplinary multimodal rehabilitation program - an explorative multivariate pilot study.
It has been suggested that alterations in inflammation molecules maintain chronic pain although little is known about how these factors influence homeostatic and inflammatory events in common chronic pain conditions. Nonpharmacological interventions might be associated with alterations in inflammation markers in blood. This study of patients with chronic pain investigates whether an interdisciplinary multimodal rehabilitation program (IMMRP) was associated with significant alterations in the plasma pattern of 68 cytokines/chemokines 1 year after rehabilitation and whether such changes were associated with clinical changes. Blood samples and self-reports of pain, psychological distress, and physical activity of 25 complex chronic pain patients were collected pre-IMMRP and at 12-month follow-up. Analyses of inflammatory proteins (cytokines/chemokines/growth factors) were performed directly in plasma using the multiplex immunoassay technology Meso Scale Discovery. This explorative pilot study found that 12 substances, mainly pro-inflammatory, decreased after IMMRP. In two other relatively small IMMRP studies, four of these proinflammatory markers were also associated with decreases. The pattern of cytokines/chemokines pre-IMMRP was associated with changes in psychological distress but not with pain or physical activity. The present study cannot impute cause and effect. These results together with the results of the two previous IMMRP studies suggest that there is a need for larger and more strictly controlled studies of IMMRP with respect to inflammatory markers in blood. Such studies need to consider responders/non-responders, additional therapies, involved pain mechanisms and diagnoses. This and the two other studies open up for developing biologically measurable outcomes from plasma. Such biomarkers will be an important tool for further development of IMMRP and possibly other treatments for patients w ith chronic pain.


Is freezing in the vaccine cold chain an ongoing issue? A literature review.
Vaccine exposure to temperatures below recommended ranges in the cold chain may decrease vaccine potency of freeze-sensitive vaccines leading to a loss of vaccine investments and potentially places children at risk of contracting vaccine preventable illnesses. This literature review is an update to one previously published in 2007 (Matthias et al., 2007), analyzing the prevalence of vaccine exposure to temperatures below recommendations throughout various segments of the cold chain. Overall, 45 studies included in this review assess temperature monitoring, of which 29 specifically assess 'too cold' temperatures. The storage segments alone were evaluated in 41 articles, 15 articles examined the transport segment and 4 studied outreach sessions. The sample size of the studies varied, ranging from one to 103 shipments and from three to 440 storage units. Among reviewed articles, the percentage of vaccine exposure to temperatures below recommended ranges during storage was 33% in wealthier countries and 37.1% in lower income countries. Vaccine exposure to temperatures below recommended ranges occurred during shipments in 38% of studies from higher income countries and 19.3% in lower income countries. This review highlights continuing issues of vaccine exposure to temperatures below recommended ranges during various segments of the cold chain. Studies monitoring the number of events vaccines are exposed to 'too cold' temperatures as well as the duration of these events are needed. Many reviewed studies emphasize the lack of knowledge of health workers regarding freeze damage of vaccines and how this has an effect on temperature monitoring. It is important to address this issue by educating vaccinators and cold chain staff to improve temperature maintenance and supply chain management, which will facilitate the distribution of potent vaccines to children.


Investigation of the glyoxysome-peroxisome transition in germinating cucumber cotyledons using double-label immunoelectron microscopy.
Microbodies in the cotyledons of cucumber seedlings perform two successive metabolic functions during early postgerminative development. During the first 4 or 5 d, glyoxylate cycle enzymes accumulate in microbodies called glyoxysomes. Beginning at about day 3, light-induced activities of enzymes involved in photorespiratory glycolate metabolism accumulate rapidly in microbodies. As the cotyledonary microbodies undergo a functional transition from glyoxysomal to peroxisomal metabolism, both sets of enzymes are present at the same time, either within two distinct populations of microbodies with different functions or within a single population of microbodies with a dual function. We have used protein A-gold immunoelectron microscopy to detect two glyoxylate cycle enzymes, isocitrate lyase (ICL) and malate synthase, and two glycolate pathway enzymes, serine:glyoxylate aminotransferase (SGAT) and hydroxypyruvate reductase, in microbodies of transition-stage (day 4) cotyledons. Double-label immunoelectron microscopy was used to demonstrate directly the co-existence of ICL and SGAT within individual microbodies, thereby discrediting the two-population hypothesis. Quantitation of protein A-gold labeling density confirmed that labeling was specific for microbodies. Quantitation of immunolabeling for ICL or SGAT in microbodies adjacent to lipid bodies, to chloroplasts, or to both organelles revealed very similar labeling densities in these three categories, suggesting that concentrations of glyoxysomal and peroxisomal enzymes in transition-stage microbodies probably cannot be predicted based on the apparent associations of microbodies with other organelles.


Facet-Specific Photocatalytic Degradation of Extracellular Antibiotic Resistance Genes by Hematite Nanoparticles in Aquatic Environments.
The persistence of extracellular antibiotic resistance genes (ARGs) in aquatic environments has attracted increasing attention due to their potential threat to public health and the environment. However, the fate of extracellular ARGs in receiving water remains largely unknown. This study investigated the influence of hematite nanoparticles, a widespread natural mineral, on the photodegradation of extracellular ARGs in river water. Results showed that under exposure to visible light, hematite nanoparticles, at environmental concentrations, resulted in a 3-5 orders of magnitude reduction in extracellular ARGs. This photodegradation of extracellular ARGs is shown to be facet-dependent; the (001) facet of hematite demonstrates a higher removal rate than that of the (100) facet, which is ascribed to its enhanced adsorption capability and higher hydroxyl radical (•OH) production. Density functional theory (DFT) calculations corroborate this finding, indicating elevated iron density, larger adsorption energy, and lower energy barrier of •OH formation on the (001) facet, providing more active sites and •OH generation for extracellular ARG interaction. Gel electrophoresis and atomic force microscopy analyses further confirm that the (001) facet causes more substantial damage to extracellular ARGs than the (100) facet. These findings pave the way for predicting the photodegradation efficiency of hematite nanoparticles with varied facets, thereby shedding light on the inherent self-purification capacity for extracellular ARGs in both natural and engineered aquatic environments.


Tobacco constituents are mitogenic for arterial smooth-muscle cells.
Tobacco glycoprotein (TGP) purified from flue-cured tobacco leaves, tar-derived material (TAR), the water soluble, nondialyzable, delipidized extract of cigarette smoke condensate, rutin-bovine serum albumin conjugates, quercetin, and chlorogenic acid are mitogenic for bovine aortic smooth-muscle cells, but not adventitial fibroblasts. The mitogenicity appears to depend on polyphenol epitopes on carrier molecules. Ellagic acid, another plant polyphenol, inhibited arterial smooth-muscle proliferation. These results suggest that a number of ubiquitous, plant-derived substances may influence smooth-muscle cell proliferation in the arterial wall.


Evaluation of colour parameters and antioxidant activities of fruit wines.
The evaluation of oenological colorimetric indexes, CIELAB parameters, total phenols and antioxidant activities has been studied in different fruit wines made from black mulberry, blackberry, quince, apple, apricot, melon, red raspberry, bilberry, sour cherry and strawberry. The highest value of antioxidant activities and total phenolic contents were determined in bilberry, blackberry and black mulberry wines (61.80%, 1161 mg/l gallic acid equivalents; 60.00%, 1232 mg/l gallic acid equivalents; 58.10%, 1081 mg/l gallic acid equivalents), respectively. The highest values for A420 nm, A520 nm, A620 nm, the proportion of blue, wine colour, wine total colour of pigments, wine polymeric pigment colour and K-K values logarithmic colour intensity) were determined in bilberry fruit wine. Positive correlation was found between antioxidant activities and total phenols (r=0.958, P = 0.001). The results of grouping of different parameters in n-dimensional space with different fruit wines demonstrated the importance of bilberry, blackberry and black mulberry wines as natural antioxidants and colourants.


Monoamino Oxidase A Gene Single-Nucleotide Polymorphisms and Methylation Status and the Risk of Violent Suicide Attempts in Affective Disorder Patients.
Background: When investigating the neurobiology of suicidal behavior, Monoamino Oxidase A (MAOA) is one of the prime suspects to consider. Interestingly, MAOA dysregulation has also been associated with violent behavior in previous publications. In the present study, we aimed to establish an association between polymorphisms of the MAOA gene and methylation status of the MAOA gene Exon I, and suicide attempts with violent methods in a sample of affective disorder patients. Methods: Eight hundred fourteen Caucasian affective disorder patients were assessed at the Department of Psychiatry and Psychotherapy of the Medical University Vienna, the Karl Landsteiner University for Health and Science and Zentren für seelische Gesundheit, BBRZ-Med Leopoldau. An assemblage of psychiatric interviews was performed (e.g., SCAN, HAMD, SBQ-R, CTQ) and DNA samples of peripheral blood cells were collected for Sequenom MassARRAY® iPLEX Gold genotyping and Multiplexed and Sensitive DNA Methylation Testing. Results: Female affective disorder patients with a history of violent suicide attempt were found to have a significantly increased frequency of the AA genotype in the rs5906957 single nucleotide polymorphism (p = 0.003). Furthermore, the MAOA gene exon I promoter region showed significantly decreased methylation in female violent suicide attempter(s) as opposed to female affective disorder patients who had no history of suicide attempt or no history of suicide attempt with violent method. Limitations: The small sample size hampers to reveal small genetic effects as to be expected in psychiatric disorders. Conclusions: This study offers promising findings about associations between the MAOA gene and violent suicide especially in women.


Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models.
Syzygium aromaticum, a medicinal plant commonly known as clove, is used to treat toothache, respiratory disorders, inflammation, and gastrointestinal disorders. From the flower buds of S. aromaticum, it is possible to obtain an essential oil comprised of a mixture of aliphatic and cyclic volatile terpenes and phenylpropanoids, being eugenol as the main component. The aims of this study were: (1) to extract the essential oil of the flower buds of S. aromaticum, (2) to identify and quantify the main component of the essential oil, and (3) to evaluate its antiulcer activity using different animal models. Assays were performed using the following protocols in rats: indomethacin-induced and ethanol/HCl-induced ulcer model. Both essential oils from S. aromaticum and eugenol displayed antiulcer activities in the rat models of indomethacin- and ethanol-induced ulcer. Studies focusing on the possible mechanisms of gastroprotection were also undertaken using the following experiments: evaluation of gastric secretion by the pylorus-ligated model, determination of mucus in gastric content, participation of nitric oxide (NO) and endogenous sulfhydryl in gastric protection. The results show that there was no significant effect on the volume of gastric juice and total acidity. However, the quantification of free gastric mucus showed that the clove oil and eugenol were capable of significantly enhancing mucus production. With regard to the NO and endogenous sulfhydryls, the results demonstrated that the gastroprotection induced by clove oil and eugenol are not related to the activities of the nitric oxide and endogenous sulfhydryls. No sign of toxicity was observed in the acute toxicity study. In conclusion, the results of this study show that essential oil of S. aromaticum, as well as its main component (eugenol), possesses antiulcer activity. The data suggest that the effectiveness of the essential oil and eugenol is based on its ability to stimulate the synthesis of mucus, an important gastroprotective factor. However, further pharmacological and toxicological investigations are required to enable its use for the treatment of gastric ulcer.


Current Topics and Practical Considerations of Cytology Practice in Lung Cancer: Reflexions from the Lung Symposium at the 42nd European Congress of Cytology, Malmö, 2019.
In June 2019, a lung symposium was held at the 42nd European Congress of Cytology in Malmö, Sweden. Due to the current importance of cytological samples in the diagnoses and molecular analysis to set up the utmost management of lung cancer patients, cytologists from different countries shared the experience of their institutions. The place of the cytological samples gains more and more importance on the potential long-term survival gain through personalized medicine and this harbors the improvement of the guidelines both in pathology and cytology field. In this symposium, the new 6-tiered reporting system for pulmonary cytology proposed by the Papanicolaou Society of Cytopathology and detailed cytomorphological approach to lung carcinoma including lookalike lesions and DNA- and RNA-based analysis of cytology material have been discussed. The cytopathologist plays a pivotal role in ensuring success of a correct triage for the cytology material to be sure of the adequacy and quality of the yield from the rapid on-site evaluation till the report which should encompass molecular profile in rational patient management.


The impact of numeric and graphic displays of ST-segment deviation levels on cardiologists' decisions of reperfusion therapy for patients with acute coronary occlusion.
The study purpose is to determine whether numeric and/or graphic ST measurements added to the display of the 12-lead electrocardiogram (ECG) would influence cardiologists' decision to provide myocardial reperfusion therapy. Twenty ECGs with borderline ST-segment deviation during elective percutaneous coronary intervention and 10 controls before balloon inflation were included. Only 5 of the 20 ECGs during coronary balloon occlusion met the 2007 American Heart Association guidelines for ST-elevation myocardial infarction (STEMI). Fifteen cardiologists read 4 sets of these ECGs as the basis for a "yes/no" reperfusion therapy decision. Sets 1 and 4 were the same 12-lead ECGs alone. Set 2 also included numeric ST-segment measurements, and set 3 included both numeric and graphically displayed ST measurements ("ST Maps"). The mean (range) positive reperfusion decisions were 10.6 (2-15), 11.4 (1-19), 9.7 (2-14), and 10.7 (1-15) for sets 1 to 4, respectively. The accuracies of the observers for the 5 STEMI ECGs were 67%, 69%, and 77% for the standard format, the ST numeric format, and the ST graphic format, respectively. The improved detection rate (77% vs 67%) with addition of both numeric and graphic displays did achieve statistical significance (P < .025). The corresponding specificities for the 10 control ECGs were 85%, 79%, and 89%, respectively. In conclusion, a wide variation of reperfusion decisions was observed among clinical cardiologists, and their decisions were not altered by adding ST deviation measurements in numeric and/or graphic displays. Acute coronary occlusion detection rate was low for ECGs meeting STEMI criteria, and this was improved by adding ST-segment measurements in numeric and graphic forms. These results merit further study of the clinical value of this technique for improved acute coronary occlusion treatment decision support.


When No One Notices: Disorders of Consciousness and the Chronic Vegetative State.
On January 5, 2019, the Associated Press reported that a woman thought to have been in the vegetative state for over a decade gave birth at a Hacienda HealthCare facility. Until she delivered, the staff at the Phoenix center had not noticed that their patient was pregnant. The patient was also misdiagnosed. Misdiagnosis of patients with disorders of consciousness in institutional settings is more the norm than the exception. Misdiagnosis is also connected to a broad and extremely significant change in the understanding of the vegetative state-a change that the field of bioethics has not yet fully taken into account. In September 2018, the American Academy of Neurology, the American College of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research issued a comprehensive evidence-based review on disorders of consciousness and an associated practice guideline on the care of these patients. These landmark publications update the 1994 Multi-Society Task Force Report on the Vegetative State, which subcategorized the persistent vegetative state as either persistent (once the vegetative state lasted one month) or permanent (once the vegetative state lasted three months after anoxic injury or twelve months after traumatic injury). Noting that 20 percent of patients thought to be permanently unconscious might regain some level of consciousness, the new guideline has eliminated the permanent vegetative state as a diagnostic category, replacing it with the chronic vegetative state.


Sulfate-Centered Sodium-Icosahedron-Templated Uranyl Peroxide Phosphate Cages with Uranyl Bridged by μ-η1:η2 Peroxide.
Two novel hybrid uranyl peroxide phosphate cage clusters, designated U20P6 and U20P12, contain peroxide bridges between uranyl in an unusual μ-η1:η2 configuration, as well as the common μ-η2:η2 configuration. These appear to be the only high-nuclearity metal peroxide complexes containing μ-η1:η2 peroxide bridges, and they are unique among uranyl peroxide cages. Both clusters contain 20 uranyl polyhedra, and U20P6 and U20P12 contain 6 and 12 phosphate tetrahedra, respectively. The 20 uranyl polyhedra in both cages are arranged on the vertices of distorted topological dodecahedrons (20 vertex fullerenes). Each cage is completed by phosphate tetrahedra and is templated by a sulfate-centered Na12 cluster with the Na cations defining a regular convex isocahedron. Whereas μ-η2:η2 peroxides are essential features of uranyl peroxide cages, where they form equatorial edges of uranyl hexagonal bipyramids, the μ-η1:η2 peroxide groups in U20P6 and U20P12 are associated with strong distortions of the uranyl polyhedra. Formation of U20P6 and U20P12 is a further demonstration of the pliable nature of uranyl polyhedra, which contributes to the tremendous topological variability of uranyl compounds. Despite the unusual structure and highly distorted polyhedral geometries of U20P6, small-angle X-ray scattering and Raman spectra suggest its stability in the aqueous solution and solid state.


Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics.
Lymphocyte responses from 208 individuals: 20 with melanoma, 34 with colon cancer, and 4 with lung cancer (58), 18 with suspected melanoma, 28 with polyposis, and 10 with COPD (56), and 94 healthy volunteers were examined. The natural logarithm of the Olive tail moment (OTM) was plotted for exposure to UVA through 5 different agar depths (100 cell measurements/depth) and analyzed using a repeated measures regression model. Responses of patients with cancer plateaued after treatment with different UVA intensities, but returned toward control values for healthy volunteers. For precancerous conditions and suspected cancers, intermediate responses occurred. ROC analysis of mean log OTMs, for cancers plus precancerous/suspect conditions vs. controls, cancer vs. precancerous/suspect conditions plus controls, and cancer vs. controls, gave areas under the curve of 0.87, 0.89, and 0.93, respectively (P<0.001). Optimization allowed test sensitivity or specificity to approach 100% with acceptable complementary measures. This modified comet assay could represent a stand-alone test or an adjunct to other investigative procedures for detecting cancer.


Bacteria and cancer: cause, coincidence or cure? A review.
Research has found that certain bacteria are associated with human cancers. Their role, however, is still unclear. Convincing evidence links some species to carcinogenesis while others appear promising in the diagnosis, prevention or treatment of cancers. The complex relationship between bacteria and humans is demonstrated by Helicobacter pylori and Salmonella typhi infections. Research has shown that H. pylori can cause gastric cancer or MALT lymphoma in some individuals. In contrast, exposure to H. pylori appears to reduce the risk of esophageal cancer in others. Salmonella typhi infection has been associated with the development of gallbladder cancer; however S. typhi is a promising carrier of therapeutic agents for melanoma, colon and bladder cancers. Thus bacterial species and their roles in particular cancers appear to differ among different individuals. Many species, however, share an important characteristic: highly site-specific colonization. This critical factor may lead to the development of non-invasive diagnostic tests, innovative treatments and cancer vaccines.


Functional dissection of a poliovirus cis-acting replication element [PV-cre(2C)]: analysis of single- and dual-cre viral genomes and proteins that bind specifically to PV-cre RNA.
The role of the cis replication element (cre) in the 2C(ATPase) coding region of the poliovirus (PV) genome has been studied with a series of mutants derived from either a PV1 full-length genome or a replicon (P/L) containing the firefly luciferase reporter gene in place of the capsid region. Using the P/L replicon we have inserted cre elements at three different locations in the genome including the 5' nontranslated region and within the open reading frame. The successful recovery of replication of a nonviable P/L (A(5)C) mutant replicon with an artificial cre element as "rescuer," in addition to the results of site-directed mutagenesis and experiments with truncated forms of PV-cre(2C), indicated that (i) the sequence within the upper stem and loop regions contains the minimal cre RNA required for VPg uridylylation in vitro, (ii) the location of the cre RNA in the poliovirus genome is not relevant to RNA infectivity, and (iii) specific binding of 3CD(pro) to PV-cre(2C) occurs within the upper stem region and probably involves several contact residues. The role of a 14-nucleotide conserved "core" sequence among known cre structures in picornaviruses was examined by site-directed mutagenesis of individual nucleotides. In addition to a conserved AAA (4472 to 4474) triplet previously shown to be the primary RNA template for VPg uridylylation by the PV RNA polymerase 3D(pol) (E. Rieder, A. V. Paul, D. W. Kim, J. H. van Boom, and E. Wimmer, J. Virol. 74:10371-10380, 2000), we have now shown that important residues (G(4468) and A(4481)) are contained in a predicted internal bulge at the upper stem-loop of PV-cre(2C). We have further demonstrated that the viral proteins 3CD(pro) and 3C(pro) form stable complexes with a transcript PV-cre(2C) RNA that can be considered critical for VPg uridylylation.


Characterization of "lettucine", a serine-like protease from Lactuca sativa leaves, as a novel enzyme for milk clotting.
In this work we focused on the characterization of a novel plant rennet purified from lettuce leaves (Lactuca sativa L. cv Romana). The lettuce protease, lettucine, showed trypsin-like, SV8-like, and caseinolytic activities. Although the enzyme did not recognize peptides having hydrophobic amino acid residues in the P(1) position of the target bond, it did show milk-clotting activity, suggesting that different bonds rather than the Phe(105)-Met(106) of the kappa-casein might be cleaved, still inducing milk-clotting. The enzyme exhibited proteolytic activity toward alpha-casein, beta-casein, kappa-casein, and milks with different fat contents, with the highest activity observed with partially skimmed milk, total casein, and alpha- and kappa-casein. SDS-PAGE studies showed that lettucine cleaved alpha-casein, beta-casein, and kappa-casein. In particular, we showed that alpha-casein breakdown occurred even though total casein or milks were supplied, suggesting that the lettuce enzyme is able to operate a significant disorganization of the casein's micellar structure. Moreover, the proteolytic activity of the enzyme analyzed under various technological parameters, such as temperature and pH, indicated that the lettuce enzyme is highly consistent with the milk-clotting process.


Location of incisal edge position for esthetic restorative dentistry.
Restorative dentistry means just that--changing the position and morphology of teeth (when indicated) to restore the patient to a functional and esthetic occlusion. The first step considers the mandibular incisal edge position. Following that choice, the maxillary anterior teeth are evaluated for position against the lips and with the rest of the dentition, particularly the mandibular incisors and canines. When the three major determinants of incisal edge position (occlusion, phonetics, and esthetics) are used to place the anterior teeth where they will function best, all cases have the potential for a more enduring esthetic success.


The in vitro digestibility of beef varies with its inherent ultimate pH.
Animal carcasses and cuts of meat are usually differentiated and valued according to size and compositional attributes. An underappreciated variable of red meat is its inherent ultimate pH (pHu) value, which affects organoleptic and processing characteristics. This study tests the hypothesis that high pHu aged meat would be more digestible than low pHu unaged (fresh) meat. Longissimus dorsi muscles collected from 59 bull carcasses had pHu values of 5.6-6.9. These were aged for 21 days at -1.5 °C, then raw and cooked (72 °C) samples were enzymatically digested at 37 °C with pepsin (pH 1.9 for 90 min) followed by pancreatin (pH 8.0 for an additional 120 min) to simulate conditions in the stomach and small intestine, respectively. Meat proteins and peptides in the digests were separated by 1D SDS PAGE. Regardless of pHu, ageing or cooking, most sarcoplasmic and myofibrillar proteins were rapidly digested by pepsin, with concomitant release of products identified by LC-MS/MS as mainly myosin-1, -2 and -7, α-actinin-2 or -3 and tropomyosin beta and alpha chains. These products were resistant to further digestion for the entire 210 min duration of the incubation. In terms of rate and extent of digestibility of these resistant products, high pHu > low pHu (P < 0.001), whereas aged > unaged (P < 0.003), with the effect of cooking dependent on pHu and varying somewhat by protein. Overall, the digestibility of meat samples increased with increasing pHu (P < 0.001). Beef meat was highly digestible but could be further differentiated on the basis of its pHu and the ease of digestibility of proteins. Specific carcasses or cuts could be targeted to consumer groups in order to provide benefits and add value.


In prospective study using Specific Quality of Life & Outcomes Response-Venous (SQOR-V) questionnaire the recall bias had the same magnitude as the minimally important difference.
To assess whether the measurement error, and recall bias can reach magnitudes comparable to minimally important difference (MID) in symptoms scores used in chronic venous disease-specific quality of life QOL instruments, such as Specific Quality of Life & Outcomes Response-Venous (SQOR-V) questionnaire. Prospective non-randomized study of 150 patients with primary chronic venous disease. SQOR-V questionnaire was administered prior to clinical visit (in 32 patients twice), and 1 month post-treatment. Patients were asked to recall their symptoms 12 months later. Measurement error (SEM) was calculated from repeated baseline measurements. MID was derived from change in the symptom score (SS) part of the SQOR-V questionnaire at 1 month. Recall bias was calculated from 12-month recall data. SEM was 1.91, the recall bias was -3.16 (95% CI from -4.08 to -2.24), and the MID was 3.7. In the treatment group the recall bias was negative (recall more severe symptoms than they actually were at the baseline), patients in the observation group had positive recall bias. SS change moderately correlated with transition rating index (Spearman rank-order correlation 0.526, P < 0.0001), and strongly correlated with the baseline value (Pearson r = 0.84). The measurement error of patient-reported symptoms scores included in disease-specific QOL instruments is small, but recall bias is close in magnitude to MID.


Electron microscope studies of the replication of a British isolate of maedi visna virus in macrophages and skin cell lines.
The replication of EV1, a British isolate of maedi visna virus (MVV), in macrophages has not previously been studied. We therefore used transmission and scanning electron microscopy (TEM and SEM respectively) to compare the replication of EV1 in macrophages versus skin cell lines. Monocyte-derived macrophages (MDM), alveolar macrophages (AM) and skin cell lines were all permissive for replication by EV1. Virus grew rapidly and to high titers in skin cell lines and mature MDM. However replication was slower in less mature MDM or AM. Virion budding occurred through (i) cytoplasmic membranes only (skin cells), (ii) cytoplasmic and vesicular membranes (MDM) or (iii) vesicular membranes only (AM). This meant that virions accumulated in vacuoles within macrophages. Retroviral intracytoplasmic type A particles were seen in the cytoplasm of AM and MDM infected with strain EV1, but not MDM infected with strain 1514 (an Icelandic MVV strain) and were shown to contain MVV gag antigen by immunogold staining.


Anterior fontanelle real-time ultrasonography in infant hydrocephalus.
Anterior fontanelle real-time ultrasonography is a method for the rapid diagnosis and evaluation of hydrocephalus. It may be used in infants up to the age of at least 18 months. It has replaced the need for computed tomography in these patients and will become an essential part of neonatal neurology in the future.


Pathogen and host factors are needed to provoke a systemic host response to gastrointestinal infection of Drosophila larvae by Candida albicans.
Candida albicans systemic dissemination in immunocompromised patients is thought to develop from initial gastrointestinal (GI) colonisation. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but studies in mice have indicated that both neutropenia and GI mucosal damage are crucial for allowing widespread invasive C. albicans disease. Mouse models, however, provide limited applicability to genome-wide screens for pathogen or host factors - factors that might influence systemic dissemination following GI colonisation. For this reason we developed a Drosophila model to study intestinal infection by Candida. We found that commensal flora aided host survival following GI infection. Candida provoked extensive JNK-mediated death of gut cells and induced antimicrobial peptide expression in the fat body. From the side of the host, nitric oxide and blood cells influenced systemic antimicrobial responses. The secretion of SAP4 and SAP6 (secreted aspartyl proteases) from Candida was also essential for activating systemic Toll-dependent immunity.


2D fibrillar osteoid niche mimicry through inclusion of visco-elastic and topographical cues in gelatin-based networks.
Given the clinical need for osteoregenerative materials incorporating controlled biomimetic and biophysical cues, a novel highly-substituted norbornene-modified gelatin was developed enabling thiol-ene crosslinking exploiting thiolated gelatin as cell-interactive crosslinker. Comparing the number of physical crosslinks, the degree of hydrolytic degradation upon modification, the network density and the chemical crosslinking type, the osteogenic effect of visco-elastic and topographical properties was evaluated. This novel network outperformed conventional gelatin-based networks in terms of osteogenesis induction, as evidenced in 2D dental pulp stem cell seeding assays, resulting from the presentation of both a local (substrate elasticity, 25-40 kPa) and a bulk (compressive modulus, 25-45 kPa) osteogenic substrate modulus in combination with adequate fibrillar cell adhesion spacing to optimally transfer traction forces from the fibrillar ECM (as evidenced by mesh size determination with the rubber elasticity theory) and resulting in a 1.7-fold increase in calcium production (compared to the gold standard gelatin methacryloyl (GelMA)).


Implant success rates in full-arch rehabilitations supported by upright and tilted implants: a retrospective investigation with up to five years of follow-up.
The aim of this retrospective study was to investigate the cumulative success rate, the implant survival rate, and the occurrence of biological complications in implants supporting full-arch immediately loaded rehabilitations supported by upright and tilted implants. The clinical records and periapical radiographs of patients who attended follow-up visits were collected, and information was recorded regarding marginal bone loss resorption, the occurrence of peri-implant infectious diseases, and the implant survival rate. Implants were classified as successful or not successful according to two distinct classifications for implant success. A total of 53 maxillary and mandibular restorations including 212 implants were analysed, of which 56 implants were studied over the full five-year follow-up period. After five years, the cumulative success rate was 76.04% according to the Misch classification and 56.34% according to the Albrektsson classification. The cumulative implant survival rate was 100%, although one implant was found to be affected by peri-implantitis at the second follow-up visit. The cumulative success rate of the implants dropped over time, corresponding to the progression of marginal bone resorption. The prevalence of peri-implantitis was very low, and the implant survival rate was not found to be related to the cumulative success rate.


Quiet ego is associated with positive attitudes toward Muslims.
Well-known predictors of prejudice toward Muslims include social dominance and authoritarianism. However, a gap exists for variables reflecting a rejection or mitigation of ideological motivations associated with prejudice toward Muslims. We examined if quiet ego was related to positive attitudes toward Muslims, and whether this could be explained by lower levels of authoritarianism, social dominance, and the motivation to express prejudice. We explored this possibility across two studies of adults in the United States (N = 376; N = 519). In Study 1, regression results showed quiet ego was directly associated with positive attitudes toward Muslims. Study 2 utilized path analyses and found that the direct relationship between quiet ego and positive attitudes toward Muslims was explained by associations between quiet ego and lower endorsement of authoritarianism, social dominance, and the internal motivation to express prejudice toward Muslims. Moreover, these associations held when accounting for several correlates of intergroup attitudes.


Ovulation suppression for endometriosis.
Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an estrogen dependent condition. This hormonal dependency has prompted the therapeutic use of ovulation suppression agents, in an effort to improve subsequent fertility. To determine the effectiveness of a) ovulation suppression with danazol, medroxy progesterone acetate, gestrinone, combined oral contraceptive pills and GnRH analogues versus placebo or no treatment and b) any of the above agents versus danazol, for the treatment of endometriosis-associated subfertility. We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 30 April 2002), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 2, 2002), MEDLINE (January 1966 to December 1998), EMBASE (January 1985 to December 1997) and reference lists of articles. We also contacted manufacturers and researchers in the field. Trials comparing the interventions described above, were included if allocation to treatment was based on a random process. Six RCTs with seven treatment arms compared an ovulation suppression agent with placebo or no treatment. Ten trials were identified comparing a suppressive agent with danazol. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. 2 x 2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using Breslow-Day X2. The odds ratio for pregnancy following ovulation suppression versus placebo or no treatment was 0.74 (95%CI 0.48 to 1.15). These data were statistically homogeneous, despite the use of a variety of suppression agents. They suggest no statistically significant benefit from treatment. The odds ratio for pregnancy following all agents versus danazol, the most commonly used agent prior to the advent of gonadotropin releasing hormone agonists (GnRHa), was 1.3 (95% CI 0.97 to 1.76). When GnRHa and danazol were directly compared, the odds ratio for pregnancy across six trials, was similar to the summary statistic for all ten studies: 1.29 (95% CI 0.9 to 1.85). Again, this suggests no statistically significant difference between these interventions. These results rule out a benefit of more than a 15% increase in odds, and do not justify the risk of side effects when used as therapy for endometriosis-associated subfertility.


Protein surface matching by combining local and global geometric information.
Comparison of the binding sites of proteins is an effective means for predicting protein functions based on their structure information. Despite the importance of this problem and much research in the past, it is still very challenging to predict the binding ligands from the atomic structures of protein binding sites. Here, we designed a new algorithm, TIPSA (Triangulation-based Iterative-closest-point for Protein Surface Alignment), based on the iterative closest point (ICP) algorithm. TIPSA aims to find the maximum number of atoms that can be superposed between two protein binding sites, where any pair of superposed atoms has a distance smaller than a given threshold. The search starts from similar tetrahedra between two binding sites obtained from 3D Delaunay triangulation and uses the Hungarian algorithm to find additional matched atoms. We found that, due to the plasticity of protein binding sites, matching the rigid body of point clouds of protein binding sites is not adequate for satisfactory binding ligand prediction. We further incorporated global geometric information, the radius of gyration of binding site atoms, and used nearest neighbor classification for binding site prediction. Tested on benchmark data, our method achieved a performance comparable to the best methods in the literature, while simultaneously providing the common atom set and atom correspondences.


[Age as one of the important criteria of prostate cancer diagnostic.]
At this moment differential diagnostic of the prostate cancer (PC) needs the new, more effective ways with regard of multifactor analysis. One of this factor is patient's age. Men older than 45 years old have expressed involution changes of prostate tissues. This fact must be take into account in valuation morphologic and laboratory criteria's in PC. The goal of the investigation is to take into account age-related changes of the prostate volume and laboratory criteria of blood analysis in PC. 632 patients in age from 42 to 88 years old were exanimated by trans rectal ultrasound examination (TRUS) method (volume parameters of the prostate) and by levels of prostate-specific antigen (PSA) and (-2) pro-PSA in blood. The increase of patient's age correlated with increase of the density of transient, peripheral and central zones of prostate. It correlates with the probability of the frequency of PC verification. Levels of PSA and 2-pro-PSA in blood of PC patients increase during the transition from middle to elderly age in 1,4-2,8 times. Thus the information, which was obtained during the examination of volume prostate characteristics by TRUS method and laboratory diagnostic of PC, must take to account patient's age.


Visual imagery influences attentional guidance during visual search: Behavioral and electrophysiological evidence.
Recent behavioral studies have shown that color imagery can benefit visual search when it is congruent with an upcoming target. In the present study we investigated whether this color imagery benefit was due to the processes underlying attentional guidance, as indicated by the electrophysiological marker known as the N2pc component. Participants were instructed to imagine a color prior to each trial of a singleton search task. On some trials, the imagined color was congruent with the target, and on other trials, it was congruent with the distractors. The analyses revealed that the N2pc was present when color imagery was congruent with the search target, and absent when it was congruent with the distractors. Further, there was preliminary evidence that attentional guidance depended on the vividness of color imagery and the frequency at which participants implemented the imagery instruction. Overall, the results of the present study indicate that color imagery can influence the attentional guidance processes underlying visual search.


Hepatitis C in the general adult population of Oslo: prevalence and clinical spectrum.
The prevalence of hepatitis C (HCV) in Northern Europe has not been well described. This study aimed to estimate the prevalence and spectrum of hepatitis C infection in the general adult population of Oslo, Norway. The study was part of the Oslo Health Study 2000-2001 and included a random selection of individuals older than 30 years living in Oslo County. Sera from 11,456 participants were screened for anti-HCV (EIA-3), positive samples were confirmed (RIBA-3) and examined for HCV RNA (PCR). All anti-HCV positive patients were offered clinical evaluation. Routine biochemical liver tests were performed. Candidates for HCV treatment were asked to undergo a percutanous liver biopsy. Among 11,456 participants HCV RNA was detected in 62 (0.5%) and HCV RNA with raised serum alanine aminotransferase (ALT) in 46 (0.4%). Anti-HCV was detected in 78 (0.7%) with a peak prevalence of 1.5% among subjects 40 and 45 years old. Being anti-HCV positive was associated with being unmarried, unemployed and having low education. Anti-HCV prevalence was higher among subjects with alcohol-related problems compared to those without (4.4% versus 0.6%, P < 0.001). It was also higher among smokers compared to non-smokers (2.0% versus 0.2%, P < 0.001). In 33 liver biopsies, bridging fibrosis was seen in 8 (24%) and cirrhosis in 1 (3%). The route of transmission was injecting drug use in 67%, transfusion in 6% and unknown in 27%. In this population-based survey the prevalence of chronic hepatitis C was 0.5% and ALT was raised in 80% of those with chronic infection.


More accurate assessment of stenotic lesions in percutaneous transluminal angioplasty.
Eighty patients underwent percutaneous transluminal dilatation and recanalisation of atheromatous lesions of the arteries of the lower extremities in the University Hospital of Maastricht in the period of 1980 to 1984. Out of 80 attempted procedures of the iliac and femoro-popliteal tract 71 (89%) were technically possible and were considered initially successful. In all cases of iliac artery lesions a retrograde arteriogram was performed prior to PTA. Intra-arterial pressure measurements at rest and after hyperemia were used for exact assessment of the hemodynamic significance of the stenosis before and after PTA. A follow-up of all patients successfully treated by angioplasty was performed. The early hemodynamic success rate of PTA for iliac lesions was 90 per cent and for femoral-popliteal segment 83 per cent. There was no morbidity or mortality. The cumulative 3-year patency rate for both segments was 74 per cent.


Abdominal Wall Leiomyoma: A Case Report.
Fibroma or leiomyoma is the most common benign tumor of the female reproductive system, which is usually found in the uterus, but may also occur in other places, such as the ovary, the broad ligament, and in rare cases in the abdominal wall. The formation of the abdominal wall leiomyoma may result from the implantation of myometrium tissue following surgical removal of the uterine leiomyoma, but sometimes these masses occur in a person who has no history of myomectomy. This case was a patient who became a candidate for laparoscopy due to abnormal uterine bleeding and pain in the right upper quadrant of the abdomen and ovarian mass. The patient underwent laparotomy due to the inability of surgeons to insert the veress needle because of the presence of mass in the abdominal wall. The pathologic report of the abdominal mass was leiomyoma. This article has been approved by the Ethics Committee of the University (6562276). The formation of myoma on the abdominal wall is rare but given the fact that leiomyoma can be created at each part of the body with smooth muscles, including the anterior abdominal wall, this diagnosis should be considered for the differential diagnosis of abdominal masses.


Diagnosing Lyme disease: often simple, often difficult.
Lyme disease has as its hallmark erythema migrans. However, it is only present in about one half of the patients who contract this disease. In its absence, the diagnosis of Lyme disease may be difficult. It depends upon a compatible history of exposure and clinical signs and symptoms together with positive results of serologic testing. Unfortunately, seronegativity for antibody to the pathogen may occur both during the first six weeks of infection and be chronic due to the reactive antibody being bound in immune complexes. The selective use of new diagnostic tests may be required to confirm the diagnosis. These tests include assays for antibody or antigen analysis of immune complex components, as well as polymerase chain reactions.


Using laryngeal electromyography to differentiate presbylarynges from paresis.
Differential diagnosis of patients over 64 years of age reporting hoarseness is challenging. Laryngeal electromyography (LEMG) was used to determine the status of the recurrent and superior laryngeal nerves. The authors hypothesized that individuals with hoarseness but normal LEMG would have measures similar to those of patients from previous studies with presbylarynges and significantly different from those of patients with abnormal LEMG. A retrospective chart review of acoustic, aerodynamic, endoscopic, and self-rating measures was completed for 52 individuals over 64 years of age reporting moderate to severe hoarseness. Individuals with normal LEMG had measures similar to those of patients from previous studies diagnosed with presbylarynges. The group with LEMG abnormalities was subcategorized by specific nerve(s) affected. Significant differences were found for measures between presbylarynges and unilateral but not bilateral paresis groups. Several endoscopic findings were observed more often than expected in the presbylarynges group. Using electromyography as a gold standard, the presence of any impairment in arytenoid movement had the most sensitivity (77%) in making the diagnosis of paresis, and the absence of any impairment had the most specificity (67%) in making the diagnosis of presbylarynges. LEMG may be useful in differentially diagnosing hoarseness in older patients, especially to distinguish between bilateral paresis and presbylarynges.


Basic principles of fracture treatment in children.
This review aims to summarize the basic treatment principles of fractures according to their types and general management principles of special conditions including physeal fractures, multiple fractures, open fractures, and pathologic fractures in children. Definition of the fracture is needed for better understanding the injury mechanism, planning a proper treatment strategy, and estimating the prognosis. As the healing process is less complicated, remodeling capacity is higher and non-union is rare, the fractures in children are commonly treated by non-surgical methods. Surgical treatment is preferred in children with multiple injuries, in open fractures, in some pathologic fractures, in fractures with coexisting vascular injuries, in fractures which have a history of failed initial conservative treatment and in fractures in which the conservative treatment has no/little value such as femur neck fractures, some physeal fractures, displaced extension and flexion type humerus supracondylar fractures, displaced humerus lateral condyle fractures, femur, tibia and forearm shaft fractures in older children and adolescents and unstable pelvis and acetabulum fractures. Most of the fractures in children can successfully be treated by non-surgical methods.


Biotechnological Potential of the Stress Response and Plant Cell Death Regulators Proteins in the Biofuel Industry.
Production of biofuel from lignocellulosic biomass is relatively low due to the limited knowledge about natural cell wall loosening and cellulolytic processes in plants. Industrial separation of cellulose fiber mass from lignin, its saccharification and alcoholic fermentation is still cost-ineffective and environmentally unfriendly. Assuming that the green transformation is inevitable and that new sources of raw materials for biofuels are needed, we decided to study cell death-a natural process occurring in plants in the context of reducing the recalcitrance of lignocellulose for the production of second-generation bioethanol. "Members of the enzyme families responsible for lysigenous aerenchyma formation were identified during the root hypoxia stress in Arabidopsis thaliana cell death mutants. The cell death regulatory genes, LESION SIMULATING DISEASE 1 (LSD1), PHYTOALEXIN DEFICIENT 4 (PAD4) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) conditionally regulate the cell wall when suppressed in transgenic aspen. During four years of growth in the field, the following effects were observed: lignin content was reduced, the cellulose fiber polymerization degree increased and the growth itself was unaffected. The wood of transgenic trees was more efficient as a substrate for saccharification, alcoholic fermentation and bioethanol production. The presented results may trigger the development of novel biotechnologies in the biofuel industry.


Estimating the relative contribution of dNTP pool imbalance and APOBEC3G/3F editing to HIV evolution in vivo.
The human immunodeficiency virus (HIV) has a genome that is rich in adenine, and its rapid evolution shows an observed bias of guanine (G) to adenine (A) mutations. Two mechanisms have been proposed to explain these properties: (1) an imbalance in dNTP pool concentrations which drives the misincorporation process during reverse transcription, and (2) cytidine deamination by the APOBEC3G/3F restriction factor, causing G to A mutations most notably in specific dinucleotide contexts. Although crucial to understanding HIV evolution, current estimates on misincorporation bias during the replication cycle are based on scarce in vitro measurements. In this work, HIV partial pol sequences obtained for drug resistance testing purposes are analyzed using likelihood methods to estimate various models of HIV misincorporation bias in vivo. The technique is robust to selection on the amino acid sequence and selection against CpG dinucleotides. A model where misincorporations are explained only by an imbalance in dNTP pool concentrations, together with a preference for transitions versus transversions, explained 98% (95% confidence interval [C.I.] 93-100) of the observed variation in freely estimated misincorporation rates. Although dinucleotide context was responsible for variation in misincorporation probabilities, this variation was not specific for G to A mutations implying that the footprint of APOBEC3G/3F editing could not be detected. These results indicate that an imbalance in dNTP pool concentrations explains most of the bias in HIV nucleotide misincorporations, while the effect of editing by APOBEC3G/3F on HIV evolution, based on its dinucleotide specificity, could not be observed in this study.


Foot massage: effectiveness on postoperative pain in breast surgery patients.
The aim of this study was to determine the effect of foot massage on pain after breast surgery, and provide guidance for nurses in nonpharmacologic interventions for pain relief. This was a quasiexperimental study with a total of 70 patients who had undergone breast surgery (35 in the experimental group and 35 in the control group). Patients in the control group received only analgesic treatment, whereas those in the experimental group received foot massage in addition to analgesic treatment. Patients received the first dose of analgesics during surgery. As soon as patients came from the operating room, they were evaluated for pain severity. Patients whose pain severity scored ≥4 according to the Short-Form McGill Pain Questionnaire were accepted into the study. In the experimental group, pain and vital signs (arterial blood pressure, pulse, and respiration) were evaluated before foot massage at the time patients complained about pain (time 0) and then 5, 30, 60, 90, and 120 minutes after foot massage. In the control group, pain and vital signs were also evaluated when the patients complained about pain (time 0) and again at 5, 30, 60, 90, and 120 minutes, in sync with the times when foot massage was completed in the experimental group. A patient information form was used to collect descriptive characteristics data of the patients, and the Short-Form McGill Pain Questionnaire was used to determine pain severity. Data were analyzed for frequencies, mean, standard deviation, chi-square, Student t, Pillai trace, and Bonferroni test. The results of the statistical analyses showed that patients in the experimental group experienced significantly less pain (p ≤ .001). Especially notable, patients in the experimental group showed a decrease in all vital signs 5 minutes after foot massage, but patients in the control group showed increases in vital signs except for heart rate at 5 minutes. The data obtained showed that foot massage in breast surgery patients was effective in postoperative pain management.


Computers in radiotherapy.
Radiotherapy is one of the earliest fields in Medicine in which computers have made an inroad. The main uses of computers, which include treatment planning, dose calculations, localisation of tumours, verification of patient setups and radiation beam data acquisition, are highlighted in this paper. It is believed that a modern Radiotherapy department cannot function optimally without some form of computing facilities. With advances made in dose calculation algorithms, and in high performance computers, it is expected that the target of 3% accuracy dose calculations can be achieved in treatment planning.


Coronary artery bypass surgery in diabetic patients - risk factors for sternal wound infections.
The incidence of sternal wound infections (SWI) after coronary artery bypass surgery (CABG) as reported worldwide is low. However, it is associated with significant increase of postoperative mortality and treatment costs. The major risk factors discussed are diabetes mellitus and bilateral IMA harvesting of the internal mammary artery. This study analyses data of 590 patients receiving CABG concerning the risk factors for SWI. Sternal wound infections occur significantly more often in diabetic patients, one crucial and significant additional risk factor is obesity.


Plasma catecholamines and angiotensin-converting enzyme activity in hypertensive subjects with positive rollover tests.
The rollover test is useful in predicting and identifying subjects developing hypertensive disorders of pregnancy. The mechanisms responsible for positive tests are unclear, but a greater release of pressor substances occurring in subjects with positive tests has been proposed. The authors measured and compared heart rate, diastolic blood pressure, plasma norepinephrine and epinephrine levels, and serum angiotensin-converting enzyme activity in ten pregnant subjects with positive rollover tests and seven control subjects with negative rollover tests at 29 to 36 weeks' gestation. Resting levels of epinephrine were significantly lower in subjects with positive rollover tests than in the control group. Plasma levels of epinephrine increased significantly during the positive rollover tests. Basal angiotensin-converting enzyme activity was significantly increased in subjects with positive tests and may play a major role in the altered cardiovascular sensitivity to pressor substances resulting in positive tests.


Preparing your practice for ICD-10.
In August 2012, the Department of Health and Human Services ruled that the ICD-10 implementation deadline would be postponed to October 1,2014. Even with this extended deadline, providers should begin preparing for the transition now. This article delivers advice to help providers with ICD-10, with suggestions such as identifying how different areas of your business could be impacted by ICD-10 and considering how to establish new processes to avoid reimbursement delays. Providers also should start training staff to familiarize them with ICD-10 codes, and collaborate with practice management system vendors to ensure they can handle ICD-10 claims. While the transition to ICD-10 will require significant preparation from providers and the rest of the industry, we will see real benefits once ICD-10 has been fully implemented, including better documentation of clinical data, greater consistency in reporting of public health trends, and reduced number of rejected claims due to coding inefficiencies.


Donor cell expansion is delayed following nonablative in utero transplantation to treat murine mucopolysaccharidosis type VII.
To block development of progressive childhood diseases, in utero transplantation (IUTx) requires immediate and significant donor peripheral blood (PB) cell amplification. To date, negligible and nontherapeutic donor PB cell levels have been observed postnatally, except in patients with immunodeficiency diseases. Donor cell fate in utero still is not clear. Ease of identifying and quantifying beta-glucuronidase (GUSB)-expressing donor cells in GUSB-null mucopolysaccharidosis type VII (MPSVII) mouse recipients allowed us to evaluate temporal donor cell engraftment and amplification post-IUTx. Like humans, MPSVII mice are unable to catabolize lysosomal glycosaminoglycans and progressively develop severe storage disease unless they are treated early in life.IUTx recipients were nonablated MPSVII fetuses and genetically stem cell-deficient, and hence myeloablated, W(41)/W(41) MPSVII fetuses. Donor GUSB+ cells were identified and counted in histochemical tissue sections. Quantitative results were confirmed by flow cytometry, enzyme analysis, and histopathology. Whereas GUSB+ cells engraft in most tissues in utero, significant amplification does not occur until the first postnatal week in the nonablated MPSVII hosts. In contrast, genetically myeloablated MPSVII recipients display widely distributed donor cell replacement accompanied by extensive amplification in utero. In both models, storage is alleviated in adult tissues with significant donor cell repopulation. To become therapeutic, IUTx must overcome the limitations of donor cell expansion in the highly competitive fetal environment. Fortunately, nonablative mechanisms to amplify cells in utero are coming on line.


Direct comparison of 111In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging.
Radiolabelled Affibody molecules have demonstrated a potential for visualization of tumour-associated molecular targets. Affibody molecules (7 kDa) are composed of three alpha-helices. Recently, a smaller two-helix variant of Affibody molecules (5.1 kDa) was developed. The aim of this study was to compare two- and three-helix HER2-targeting Affibody molecules directly in vivo. The three-helix Affibody molecule ABY-002 and the two-helix Affibody molecule PEP09239 were labelled with (111)In at the N-termini via DOTA chelator. Tumour-targeting properties were directly compared at 1 and 4 h after injection in mice bearing SKOV-3 xenografts with high HER2 expression and LS174T xenografts with low HER2 expression. The dissociation constants (K(D)) for HER2 binding were 78 pM for the three-helix Affibody molecule and 2.1 nM for the two-helix Affibody molecule. (111)In-PEP09239 cleared more rapidly from the blood. In xenografts with high HER2 expression, the uptake of (111)In-ABY-002 was significantly higher than that of (111)In-PEP09239. The tumour-to-blood ratio was higher for (111)In-PEP09239 at 4 h after injection, while there was no significant difference in other tumour-to-organ ratios. The tumour uptake of (111)In-ABY-002 was eightfold higher than that of (111)In-PEP09239 in xenografts with low expression. Tumour-to-blood ratios were equal in this case, but other tumour-to-organ ratios were appreciably higher for the three-helix variant. For tumours with high HER2 expression, two-helix HER2-targeting Affibody molecules can provide higher tumour-to-blood ratio at the cost of lower tumour uptake. In the case of low expression, both tumour uptake and tumour-to-organ ratios are appreciably higher for three-helix than for two-helix HER2-targeting Affibody molecules.


Cloning and expression of an Arabidopsis gene encoding a putative peroxisomal ascorbate peroxidase.
An Arabidopsis 14-3-3 protein, AFT1, was used as a 'bait' in the two-hybrid system to identify its interacting proteins. One of the candidate proteins, APX3, was identified as a putative peroxisomal membrane-bound ascorbate peroxidase. Ascorbate peroxidases are important defense enzymes that protect plant cells from oxidative stress damage. DNA blot analysis indicates that APX3 is encoded by a single-copy gene in the Arabidopsis genome. RNA blot analyses show that APX3 transcript levels increase slightly in response to cold, UV light, and treatments with hydrogen peroxide and paraquat. The activity of APX3 in Arabidopsis may be controlled in two ways: its enzymatic activity through protein-protein interactions and its transcription by transcriptional or posttranscriptional regulation.


Extremity Soft Tissue Sarcoma: A Multi-Institutional Validation of Prognostic Nomograms.
Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients. Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms. A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes. Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.


Radiophosphate (32-PO4) incorporation into phosphatidic acid of lead-poisoned and normalred cells.
Radiophosphate incorporation into phosphatidic acid is decreased in the red cells of lead-poisoned humans and rabbits. The decrease in activity is not related to the length of red cell survival nor to the differences in osmotic fragility observed in the lead-poisoned cells. Incorporation of radiophosphate into phosphatidic acid of normal red cells is sulfhydryl dependent and occurs at the cell surface. Lipid composition of the red cell membrane of the lead-poisoned humans and rabbits is normal.


Use of angiotensin-converting enzyme inhibitor therapy and dose-related outcomes in older adults with new heart failure in the community.
To evaluate the dose-related benefit of angiotensin-converting enzyme (ACE) inhibitor therapy among older adults with heart failure and to evaluate whether low-dose ACE inhibitor therapy is better than none. Observational cohort study. Community-dwelling older adults in Ontario, Canada. We identified 16539 adults 66 years or older who survived 45 days following their first heart failure hospitalization discharge. Multivariate techniques including propensity scores were used to study the association between the dose of ACE inhibitor therapy dispensed and 3 outcomes: survival, survival or heart failure rehospitalization, and survival or all-cause hospitalization at 1 year of follow-up. Logistic regression models explored the association between initial dose dispensed and subsequent dose reduction or drug cessation. Overall, 10793 (65.3%) of patients were dispensed ACE inhibitor therapy, with more than a third (3935; 36.5%) initiated on low-dose therapy. Relative to dispensing of low-dose ACE inhibitor therapy, nonuse was associated with increased mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.02 to 1.22). Dispensing medium-dose therapy provided a benefit similar to low-dose (HR, 0.94; CI, 0.86 to 1.03) and dispensing of high-dose therapy was associated with improved survival benefit (HR, 0.76; CI, 0.68 to 0.85). Relative to dispensing of low-dose ACE inhibitor therapy, dispensing high-dose conferred a benefit (HR, 0.87; CI, 0.80 to 0.95) on the composite outcome of 1-year mortality or heart failure hospitalization and the composite outcome of 1-year mortality or all-cause hospitalization (HR, 0.87; CI, 0.81 to 0.93). Relative to those dispensed low-dose ACE inhibitor therapy, those initially dispensed high-dose therapy were twice as likely to have their subsequent dose reduced or the therapy discontinued (odds ratio, 2.36; CI, 2.07 to 2.69). Our findings suggest that when possible, older adults should be titrated to the higher doses of ACE inhibitor therapy evaluated in clinical trials. If older adults cannot tolerate higher doses, then low-dose ACE inhibitor therapy is superior to none. High-dose ACE inhibitor therapy is not as well tolerated as lower doses.


Asymmetric chiral metamaterial circular polarizer based on four U-shaped split ring resonators.
An asymmetric chiral metamaterial structure is constructed by using four double-layered U-shaped split ring resonators, which are each rotated by 90° with respect to their neighbors. The peculiarity of the suggested design is that the sizes of the electrically and magnetically excited rings are different, which allows for equalizing the orthogonal components of the electric field at the output interface with a 90° phase difference when the periodic structure is illuminated by an x-polarized wave. As a result, left-hand circular polarization and right-hand circular polarization are obtained in transmission at 5.1 GHz and 6.4 GHz, respectively. The experiment results are in good agreement with the numerical results.


Why would I help my coworker? Exploring asymmetric task dependence and the self-determination theory internalization process.
Research on power suggests asymmetric task dependence (sending work resources to a coworker and receiving little in return) should create a power imbalance and promote selfishness. In contrast, work design theory suggests asymmetry can lead to felt responsibility, but this link has not been tested and its theory remains underdeveloped. Drawing on self-determination theory (SDT), this article argues that work design characteristics can encourage the SDT internalization process-the transformation of external reasons for behavior into internal reasons. Two experiments demonstrate asymmetry encourages felt responsibility for the dependent's task, which helps explain the amount of help provided to the dependent. The author proposes felt responsibility indicates the extent to which an external task has been internalized as a self-directed motivation. This article clarifies how task dependence is different from power and develops an important and understudied aspect of SDT: how work design characteristics are transformed into internalized motivations. (PsycINFO Database Record


ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure.
Primary ovarian insufficiency (POI) is a frequent disorder that affects ~1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone (FSH), leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene variants, most cases remain idiopathic. The aim of the present study was to identify and validate functionally new sequence variants in ATG (autophagy-related genes) leading to POI. We have reanalyzed, in silico, the exome sequencing data from a previously reported work performed in 69 unrelated POI women. Functional experiments using a classical hallmark of autophagy, the microtubule-associated protein 1 light chain 3β (LC3), were then used to link these genes to this lysosomal degradation pathway. We venture a functional link between ATG7 and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a decrease in autophagosome biosynthesis and consequently to an impairment of autophagy, a key biological process implicated in the preservation of the primordial follicles forming the ovarian reserve. Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI.


Modular Approach to Selected Configuration Interaction in an Arbitrary Spin Basis: Implementation and Comparison of Approaches.
A modular selected configuration interaction (SCI) code has been developed that is based on the existing Monte-Carlo configuration interaction code (MCCI). The modularity allows various selection protocols to be implemented with ease and allows for fair comparison between wave functions built via different criteria. We have initially implemented adaptations of existing SCI theories, which are based on either energy- or coefficient-driven selection schemes. These codes have been implemented not only in the basis of Slater determinants (SDs) but also in the basis of configuration state functions (CSFs) and extended to state-averaged regimes. This allows one to take advantage of the reduced dimensionality of the wave function in the CSF basis and also the guarantee of pure spin states. All SCI methods were found to be able to predict potential energy surfaces to high accuracy, producing compact wave functions, when compared to full configuration interaction (FCI) for a variety of bond-breaking potential energy surfaces. The compactness of the error-controlled adaptive configuration interaction approach, particularly in the CSF basis, was apparent with nonparallelity errors within chemical accuracy while containing as little as 0.02% of the FCI CSF space. The size-to-accuracy was also extended to FCI spaces approaching one billion configurations.


Characterizing the roles of Met31 and Met32 in coordinating Met4-activated transcription in the absence of Met30.
Yeast sulfur metabolism is transcriptionally regulated by the activator Met4. Met4 lacks DNA-binding ability and relies on interactions with Met31 and Met32, paralogous proteins that bind the same cis-regulatory element, to activate its targets. Although Met31 and Met32 are redundant for growth in the absence of methionine, studies indicate that Met32 has a prominent role over Met31 when Met30, a negative regulator of Met4 and Met32, is inactive. To characterize different roles of Met31 and Met32 in coordinating Met4-activated transcription, we examined transcription in strains lacking either Met31 or Met32 upon Met4 induction in the absence of Met30. Microarray analysis revealed that transcripts involved in sulfate assimilation and sulfonate metabolism were dramatically decreased in met32Δ cells compared to its wild-type and met31Δ counterparts. Despite this difference, both met31Δ and met32Δ cells used inorganic sulfur compounds and sulfonates as sole sulfur sources in minimal media when Met30 was present. This discrepancy may be explained by differential binding of Met31 to Cbf1-dependent promoters between these two conditions. In the absence of Met30, genome-wide chromatin immunoprecipitation analyses found that Met32 bound all Met4-bound targets, supporting Met32 as the main platform for Met4 recruitment. Finally, Met31 and Met32 levels were differentially regulated, with Met32 levels mimicking the profile for active Met4. These different properties of Met32 likely contribute to its prominent role in Met4-activated transcription when Met30 is absent.


Pressure aberrations inside the spinal canal during rear-end impact.
Minor soft tissue injuries of the cervical spine increasingly pose problems in public health. Such injuries are conveyed particularly often in rear-end automobile collisions at low impact speeds and it has been established that they may be associated with long-term impairment. As a possible cause for this type of injury it has been hypothesized that pressure pulses induced in cervical fluid compartments during the impact could damage the membrane of spinal nerve cells. To date, animal as well as cadaver experiments performed support this hypothesis. A theoretical analysis has been undertaken in order to investigate the pressure and flow pulse emerging in a cervical fluid compartment under conditions representing rear-end impacts with a Dv of 15 km/h. Using the finite element (FE) method, a three-dimensional model of the cervical spine was developed. The model consists of eight vertebrae (C1-T1), the intervertebral discs, the intervertebral joints, all the major ligaments, most of the neck muscles and the head. Additionally, a typical venous blood vessel was included. To determine the pressure behaviour inside the blood vessel, fluid-structure interaction was taken into account. For the time interval including the development of the S-shape, the pressure pulses were calculated and found to be in qualitative agreement with the reported measurements. The shear stresses acting on the vessel wall can be determined from the associated flow pulses. An extrapolation of the results into the interstitial space where nerve cells are located at this stage does not allow assessment of whether a damage threshold may be reached.


Evaluating the impact of Brexit on the pharmaceutical industry.
The UK Pharmaceutical Industry is arguably one of the most important industries to consider in the negotiations following the Brexit vote. Providing tens of thousands of jobs and billions in tax revenue and research investment, the importance of this industry cannot be understated. At stake is the global leadership in the sector, which produces some of the field's most influential basic science and translation work. However, interruptions and losses may occur at multiple levels, affecting patients, researchers, universities, companies and government. By understanding the current state of pharmaceutical sector, the potential effect of leaving the European Union (EU) on this successful industry can be better understood. This paper aims to address the priorities for negotiations by collating the analyses of professionals in the field, leading companies and non-EU member states. A government healthcare policy advisor and Chief Science Officer (CSO) for a major pharmaceutical firm were consulted to scope the paper. In these discussions, five key areas were identified: contribution, legislative processes, regulatory processes, research and outcomes, commercial risk. Multiple search engines were utilised for selecting relevant material, predominantly PubMed and Google Scholar. To supplement this information, Government documents were located using the "GOV.UK" publications tool, and interviews and commentaries were found through the Google News search function. With thorough investigation of the literature, we propose four foundations in the advancement of negotiations. These prioritise: negotiation of 'associated country' status, bilaterally favourable trade agreements, minimal interruption to regulatory bodies and special protection for the movement of workforce in the life sciences industry.


Neural correlates of virtual route recognition in congenital blindness.
Despite the importance of vision for spatial navigation, blind subjects retain the ability to represent spatial information and to move independently in space to localize and reach targets. However, the neural correlates of navigation in subjects lacking vision remain elusive. We therefore used functional MRI (fMRI) to explore the cortical network underlying successful navigation in blind subjects. We first trained congenitally blind and blindfolded sighted control subjects to perform a virtual navigation task with the tongue display unit (TDU), a tactile-to-vision sensory substitution device that translates a visual image into electrotactile stimulation applied to the tongue. After training, participants repeated the navigation task during fMRI. Although both groups successfully learned to use the TDU in the virtual navigation task, the brain activation patterns showed substantial differences. Blind but not blindfolded sighted control subjects activated the parahippocampus and visual cortex during navigation, areas that are recruited during topographical learning and spatial representation in sighted subjects. When the navigation task was performed under full vision in a second group of sighted participants, the activation pattern strongly resembled the one obtained in the blind when using the TDU. This suggests that in the absence of vision, cross-modal plasticity permits the recruitment of the same cortical network used for spatial navigation tasks in sighted subjects.


[A secondary effect of converting enzyme inhibitors: cough].
Cough associated with angiotensin-converting enzyme (ACE) inhibitors has long been considered a rare side effect. We report 8 cases, 7 with enalapril (10 to 20 mg/day) 1 with quinapril (40 mg/day) in which cough occurred after a mean duration of treatment of 39 days. In all patients, cough disappeared with a mean delay of 2 days with no other treatment than withdrawal of the drug. In 6 patients, cough was reinduced within less than a day with the same drug; in 5 patients a second reinduction with another ACE inhibitor gave the same result. These data suggest that cough is probably more frequent than it would appear from the literature. In clinical practice, if cough occurs in a patient treated with an ACE inhibitor, the drug may be continued for a few days in order to exclude an acute viral infection; if cough lasts more than a week, specific diagnostic procedures for pulmonary disease should be initiated; if it stops, the patient may be treated either for hypertension or chronic heart failure with another ACE inhibitor.


Initial experience of restorative proctocolectomy for ulcerative colitis by transanal total mesorectal rectal excision and single-incision abdominal laparoscopic surgery.
Laparoscopic surgery is well established for colon cancer, with defined benefits. Use of laparoscopy for the performance of restorative proctocolectomy (RPC) with ileoanal anastomosis is more controversial. Technical aspects include difficult dissection of the distal rectum and a potentially increased risk of anastomotic leakage through multiple firings of the stapler. In an attempt to overcome these difficulties we have used the technique of transanal rectal excision to perform the proctectomy. This paper describes the technique, which is combined with an abdominal approach using a single-incision platform (SIP). Data were collected prospectively for consecutive operations between May 2013 and October 2015, including all cases of restorative proctocolectomy with ileoanal pouch anastomosis performed laparoscopically. Only patients having a transanal total mesorectal excision (TaTME) assisted by SIP were included. The indication for RPC was ulcerative colitis (UC) refractory to medical treatment. The procedure was performed on 16 patients with a median age of 46 (26-70) years. The male:female ratio was 5:3 and the median hospital stay was 6 (3-20) days. The median operation time was 247 (185-470) min and the overall conversion rate to open surgery was 18.7%. The 30-day surgical complication rate was 37.5% (Clavien-Dindo 1 in four patients, 2 in one patient and 3 in one patient). One patient developed anastomotic leakage 2 weeks postoperatively. This initial study has demonstrated the feasibility and safety of TaTME combined with SIP when performing RPC with ileal pouch-anal anastomosis for UC.


Non-alcoholic fatty liver disease and hepatitis C infection.
Non-alcoholic fatty liver disease (NAFLD) is now recognized as one of the most important causes of chronic liver disease in Western Countries, and is the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD has increased with the global epidemic of obesity and type 2 diabetes mellitus. The pathophysiological hallmark of NAFLD is insulin resistance, associated with mediators of oxidative stress and inflammatory cytokines. Although simple steatosis by itself is generally benign, patients with histologically proven non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. Hepatitis C (HCV) is another common cause of liver disease with some potential for progression to cirrhosis. Steatosis is present in almost 50% of patients infected by HCV. Hepatic steatosis in the setting of another liver disease (such as HCV) is associated liver disease progression. In particular, significant fibrosis is observed in patients with HCV whose liver biopsies show significant steatosis or superimposed NASH. This article reviews the host and viral factors potentially involved in the interaction between NAFLD and HCV. These factors include mediators of metabolic syndrome such as adipokines, inflammatory cytokines, factors associated with oxidative stress, lipid peroxidation products, as well as apoptosis and hepatic stellate cell activation with the resultant deposition of extracellular matrix. In addition to the mediators of metabolic syndrome (host factors), hepatic steatosis can be influenced by viral factors. The most important viral factor is HCV genotype 3, which has been independently associated with hepatic steatosis. Finally, superimposed NAFLD and visceral fat are associated with lower response rates to antiviral therapy in non-genotype 3 patients. Furthermore, viral clearance is associated with the resolution of hepatic steatosis in HCV genotype 3 but not other HCV genotypes. In these genotypes, hepatic steatosis and its impact on response to therapy are related to metabolic syndrome. Thus, the management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression as well as improving the efficacy of antiviral therapy.


Distribution of the novel eNOS-interacting protein NOSIP in the liver, pancreas, and gastrointestinal tract of the rat.
Recently, a yeast 2-hybrid screen served to identify a new endothelial nitric oxide synthase (eNOS)-interacting protein (NOSIP), which causes redistribution of eNOS from the plasma membrane to intracellular compartments and reduces eNOS activity. Its in situ distribution is unknown and is reported here in comparison with that of eNOS and neuronal NOS for the rat gastrointestinal tract. Immunofluorescence was performed on acetone-fixed cryosections by using a polyclonal antiserum raised against a NOSIP-glutathione S-transferase fusion protein; specificity was verified by Western blotting. Cytoplasmic NOSIP immunoreactivity was observed in endothelial cells of some locations, e.g., the hepatic central vein, but it was mainly observed in the striated esophageal muscle; vascular, gastric, and intestinal smooth muscle; and in interstitial cells of Cajal. Nuclear NOSIP immunoreactivity was more widespread, including some myenteric neurons and several epithelial cell types of esophagus, stomach, pancreas, liver, and gut. This cellular distribution matched with that of its potential binding partner eNOS, as determined by immunohistochemistry and reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry, and eNOS, but not neuronal NOS, could be coimmunoprecipitated with NOSIP from small intestine. NOSIP coimmunoprecipitates and is widely codistributed with eNOS in nonvascular cells in the gastrointestinal tract, suggesting an involvement of eNOS/NOSIP in the regulation of gastrointestinal secretion and motility.


Involvement of a new enzyme, glyoxal oxidase, in extracellular H2O2 production by Phanerochaete chrysosporium.
The importance of extracellular H2O2 in lignin degradation has become increasingly apparent with the recent discovery of H2O2-requiring ligninases produced by white-rot fungi. Here we describe a new H2O2-producing activity of Phanerochaete chrysosporium that involves extracellular oxidases able to use simple aldehyde, alpha-hydroxycarbonyl, or alpha-dicarbonyl compounds as substrates. The activity is expressed during secondary metabolism, when the ligninases are also expressed. Analytical isoelectric focusing of the extracellular proteins, followed by activity staining, indicated that minor proteins with broad substrate specificities are responsible for the oxidase activity. Two of the oxidase substrates, glyoxal and methylglyoxal, were also identified, as their quinoxaline derivatives, in the culture fluid as secondary metabolites. The significance of these findings is discussed with respect to lignin degradation and other proposed systems for H2O2 production in P. chrysosporium.


Effects of herbicides on the concentration of poisonous compounds in plants: a review.
Herbicides may raise, lower, or not affect the concentration of poisonous compounds in plants. Herbicides, 2,4,5-T and silvex controlled Wasatch milkvetch (Astragalus miser var oblongifolius) and markedly reduced the concentration of miserotoxin, a poisonous aliphatic nitro compound. The concentration of phototoxic furocoumarins in the leaves of spring parsley (Cymopterus watsonii) decreased to nontoxic concentrations 4 to 5 weeks after treatment with 2,4-D. The hydrocyanic acid content of wild cherry (Prunus spp) decreased after treatment with 2,4-D and 2,4,5-T, but increased in Sudangrass (Sorghum halapense) after treatment with 2,4-D. The alkaloid concentration in Barbey larkspur (Delphinium barbeyi) increased after treatment with 2,4,5-T or silvex, decreased in horsetail (Equisetum palustre) after treatment with MCPA, and was unaffected in Datura after treatment with several herbicides. The effect of herbicides on nitrate concentration in plants was dependent upon the species of plant and the herbicide used.


Importance of Individual Germination Receptor Subunits in the Cooperative Function between GerA and Ynd.
Germination of Bacillus spores is triggered by the binding of specific nutrients to germinant receptors (GRs) located in the spore's inner membrane. The GRs typically consist of A, B, and C subunits, encoded by tricistronic ger operons. The Bacillus licheniformis genome contains the gerA family operons gerA, ynd, and gerK In contrast to the ABC(D) organization that characterizes gerA operons of many Bacillus species, B. licheniformis genomes contain a pentacistronic ynd operon comprising the yndD, yndE3 , yndE2 , yndF1 , and yndE1 genes encoding A, B, B, C, and B GR subunits, respectively (subscripts indicate paralogs). Here we show that B. licheniformis spores can germinate in the absence of the Ynd and GerK GRs, although cooperation between all three GRs is required for optimal germination with amino acids. Spores carrying an incomplete set of Ynd B subunits demonstrated reduced germination efficiencies, while depletion of all three Ynd B subunits restored germination of the spore population to levels only slightly lower than those of wild-type spores at high germinant concentrations. This suggests that the presence of an incomplete set of Ynd B subunits exhibits a dominant negative effect on germination and that the A and C subunits of the Ynd GR are sufficient for the cooperative functionality between Ynd and GerA. In contrast to the B subunits of Ynd, the B subunit of GerA was essential for amino acid-induced germination. This study provides novel insights into the role of individual GR subunits in the cooperative interaction between GRs in triggering spore germination.IMPORTANCE Spore-forming bacteria are problematic for the food industry, as spores can survive decontamination procedures and subsequently revive in food products, with the risk of food spoilage and foodborne disease. The Ynd and GerA germination receptors (GRs) cooperate in triggering efficient germination of Bacillus licheniformis spores when nutrients are present in the surrounding environment. This study shows that the single B subunit of GerA is essential for the cooperative function between Ynd and GerA, while the three B subunits of the Ynd GR are dispensable. The ability of GRs lacking individual subunits to stimulate germination together with other GRs could explain why ger operons lacking GR subunit genes are maintained in genomes of spore-forming species.


Formation of bone in tibial defects in a canine model. Histomorphometric and biomechanical studies.
The histomorphometric, material, and structural properties of the reparative tissue and bone that formed in a two-millimeter tibial defect in dogs were determined at two, four, eight, and twelve weeks after the operation. At two weeks, the tibial defect was filled mainly with undifferentiated connective tissue. After two weeks, the relative proportion of undifferentiated connective tissue decreased and the amount of bone progressively increased throughout the twelve weeks. New bone formed primarily by intramembranous ossification, with a small degree of endochondral ossification. At twelve weeks, bone occupied 62 per cent of the defect. The calcium content of the reparative tissue increased between four and eight weeks and then, at twelve weeks, reached a plateau of 77 per cent that of normal cortical bone. Anisotropy of the new bone that formed in the defect increased from 13.8 per cent to 26 per cent, and the mean width of the trabecular bone increased 27 per cent between the eighth and twelfth weeks. Maximum torque and torsional stiffness increased between two and eight weeks and then, by twelve weeks, the values leveled off at 44 and 29 per cent of the values for intact bone. Indentation stiffness increased between the fourth and twelfth weeks; at twelve weeks, it was 22 per cent of the stiffness of normal cortical bone. Indentation stiffness increased 283 per cent between eight and twelve weeks, despite insignificant changes in calcium content, amount of new bone, non-osseous space, water content, or volume of trabecular bone during this time. This change in indentation stiffness did correlate with increases in anisotropy of the new bone between eight and twelve weeks.


Electron microscopic study of epithelial downgrowth after penetrating keratoplasty.
An electron microscope study of 2 cases of epithelial downgrowth after penetrating keratoplasty is presented. Several differences were observed between the normal epithelium and downgrowth epithelium at the ultrastructure level. At the advancing edge of the downgrowth a flattened and fibroblastic endothelium was still present. An interaction area was observed between these 2 tissues. The epithelial downgrowth usually has 5 to 6 layers of cells and either replaces damaged endothelium or destroys it as it advances. The attachment of this downgrowth tissue to the Descemet's membrane at the centre of the graft seemed looser than attachment of a normal epithelium to Bowman's membrane. Near the host-graft junction the downgrowth epithelium, with basement membrane, was tightly attached to a fibrous retrocorneal membrane. Clinical and histological findings suggest that the absence of endothelium assists in the advance of the epithelial downgrowth, but it is not an essential factor. The causes of this downgrowth are thought to be (1) a thin host cornea; (2) incomplete cutting and wound incarceration of Descemet's membrane; and (3) tight sutures with disruption of an old cataract wound.


Time resolved Fabry-Perot measurements of cavity temperature in pulsed QCLs.
Temperature rise during operation is a central concern of semiconductor lasers and especially difficult to measure during a pulsed operation. We present a technique for in situ time-resolved temperature measurement of quantum cascade lasers operating in a pulsed mode at ~9.25 μm emission wavelength. Using a step-scan approach with 5 ns resolution, we measure the temporal evolution of the spectral density, observing longitudinal Fabry-Perot modes that correspond to different transverse modes. Considering the multiple thin layers that make up the active layer and the associated Kapitza resistance, thermal properties of QCLs are significantly different than bulk-like laser diodes where this approach was successfully used. Compounded by the lattice expansion and refractive index changes due to time-dependent temperature rise, Fabry-Perot modes were observed and analyzed from the time-resolved emission spectra of quantum cascade lasers to deduce the cavity temperature. Temperature rise of a QCL in a pulsed mode operation between -160 °C to -80 °C was measured as a function of time. Using the temporal temperature variations, a thermal model was constructed that led to the extraction of cavity thermal conductivity in agreement with previous results. Critical in maximizing pulsed output power, the effect of the duty cycle on the evolution of laser heating was studied in situ, leading to a heat map to guide the operation of pulsed lasers.


Non-Hodgkin's lymphoma in patients with human immunodeficiency virus infection in Taiwan.
Non-Hodgkin's lymphoma (NHL) is the second most common acquired immunodeficiency syndrome-defining malignancy with a high mortality rate. This study aimed to describe changes in the incidence and clinical characteristics of NHL in human immunodeficiency virus (HIV)-infected patients in a referral hospital for HIV care. The medical records of HIV-infected patients diagnosed with NHL between June 1994 and December 2006 were retrospectively reviewed. Risk stratification of each patient was evaluated using the International Prognostic Index (IPI). Case patients were followed at least for 2 years to assess the 2-year survival rates. During the 12-year period, 38 HIV-infected patients were diagnosed with NHL. Their median cluster of differentiation 4 count was 82 cells/microL (range, 2-477 cells/microL) at diagnosis. Before the introduction of highly active antiretroviral therapy (HAART) in April 1997, 9/175 HIV-infected patients (5.1%) developed NHL compared with 29/1,386 patients (2.1%) in the HAART era (p < 0.05). Although the 2-year survival rate did not differ significantly between patients diagnosed in the pre-HAART era (22.2%) and those diagnosed in the HAART era (24.1%), patients receiving HAART for more than 6 months had better survival rates (p < 0.05). A low IPI score was a good prognostic factor predictive of a patient's outcome. The incidence of NHL in HIV-infected patients declined significantly in the HAART era. Despite the introduction of HAART, the short-term survival of the patients with NHL remained poor. The IPI was a good predictor for survival.