Histone H1; a neuronal protein that binds bacterial lipopolysaccharide.
Bacterial lipopolysaccharide (LPS) is a potent inflammogen following systemic infection. Macrophages express a number of surface molecules including CD14, CD18 and the scavenger receptor that are capable of recognizing and binding LPS. Injection of the CNS with LPS produces an atypical inflammatory response including a delay in the recruitment of macrophages to the brain parenchyma. We have shown using a ligand blot overlay approach, that LPS is capable of binding to histone H1 present in brain homogenate. The ability of LPS to bind to H1 has only been previously shown for monocytes. Subsequent immunohistochemistry revealed that the anti-H1 antibody, ANA-108, stained neuronal cell bodies and was located in the membrane, possibly at the cell surface. Further experiments revealed that the H1 antigen recognized by the ANA-108 antibody was not a histone wholly restricted to the nucleus but may represent a novel CNS form of the protein. This observation has implications for the autoimmune disease systemic lupus erythematosus (SLE) due to the presence of auto-antibodies, particularly against DNA and nuclear proteins, in serum. The formation of immune complexes in various organs leads to severe dysfunction. Anti-histone antibodies are typical of the auto-antibodies found in SLE serum and the presence of the H1 antigen on the surface of neurons could provide an insight into biology underlying the neurological problems associated with SLE.


Influenza a viruses from wild birds in Guatemala belong to the North American lineage.
The role wild bird species play in the transmission and ecology of avian influenza virus (AIV) is well established; however, there are significant gaps in our understanding of the worldwide distribution of these viruses, specifically about the prevalence and/or significance of AIV in Central and South America. As part of an assessment of the ecology of AIV in Guatemala, we conducted active surveillance in wild birds on the Pacific and Atlantic coasts. Cloacal and tracheal swab samples taken from resident and migratory wild birds were collected from February 2007 to January 2010.1913 samples were collected and virus was detected by real time RT-PCR (rRT-PCR) in 28 swab samples from ducks (Anas discors). Virus isolation was attempted for these positive samples, and 15 isolates were obtained from the migratory duck species Blue-winged teal. The subtypes identified included H7N9, H11N2, H3N8, H5N3, H8N4, and H5N4. Phylogenetic analysis of the viral sequences revealed that AIV isolates are highly similar to viruses from the North American lineage suggesting that bird migration dictates the ecology of these viruses in the Guatemalan bird population.


[Determining cause of death from death certificates in public health offices--experiences with a data custodian model].
In a study on the long-term outcome after thrombolysis in patients with acute myocardial infarction, we had to ascertain the cause of death as noted in the confidential section of the official death certificate at the Public Health Office. Since current data protection legislation does not permit direct access to the death certificates we used a custodian model which strictly separates the institution storing the addresses in touch, and carries out the inquiry and the institution receiving the anonymised data for analysis. Forty Public Health Offices in ten German Bundesländer were asked for causes of death of 118 patients. Data were delivered by 35 Public Health Offices from nine Bundesländer on 106 patients (response = 89.8%). The custodian model which was often proposed as a tool for epidemiological research within the restrictive legal framework in Germany, proved to be successful in practice, with good response.


Alcohol consumption in arthritic patients: clinical and laboratory studies.
In popular belief patients with chronic arthritis take alcohol for its analgesic effect. To test this we studied by validated questionnaire the past and present alcohol consumption of 103 patients with primary osteoarthritis of the hip (OA), 95 patients with rheumatoid arthritis (RA), and 90 orthopaedic non-arthritic controls. OA men were most likely and RA men least likely to have been heavy drinkers at any time of their lives. Mean red corpuscular volume (MCV), gamma-glutamyltransferase (GGT), and serum uric acid (SUA) levels did not correlate with reported alcohol consumption. Two of 93 OA femoral heads examined had avascular change; both were from heavy drinkers. The abstemiousness of RA men compared with their OA counterparts was due to a striking increase in joint pain after drinking alcohol (p = 0.004), fear of adverse drug reactions with alcohol, and a widespread belief not expressed by OA men that 'alcohol and arthritis do not mix'.


Immunomagnetic enrichment of disseminated epithelial tumor cells from peripheral blood by MACS.
Disseminated epithelial tumor cells have been detected in the bone marrow and blood of cancer patients by means of immunocytochemical or immunofluorescent staining of cytocentrifuge slides, multiparameter flow cytometry, and reverse transcriptase-polymerase chain reaction. However, it is hardly possible using such methods to detect tumor cells at a frequency below 10(-6). To increase the sensitivity of these detection techniques we have developed a new technology for the enrichment of disseminated epithelial tumor cells from hematopoietic cell samples by high-gradient magnetic cell sorting (MACS). Cells are permeabilized and fixed and carcinoma cells are magnetically labeled specifically with an anti-cytokeratin 8 monoclonal antibody (mAb) directly conjugated to superparamagnetic microbeads. Magnetically labeled cells are enriched on high-gradient magnetic columns. Tumor cells are detected in the enriched cell fraction by flow cytometry, fluorescence microscopy, or immunocytochemisty. In this study we demonstrated the method using a model system in which five to 5,000 cells from a breast cancer cell line were seeded into blood cell samples from a healthy donor containing 1.2 x 10(8) leukocytes. Tumor cells were 10,477+/-4242 (n=25)-fold magnetically enriched, and 57.7%+/-16.9% (n=33) of the initially seeded tumor cells were recovered. Applying the method to 20-40 mL blood samples from patients with advanced carcinomas of the breast, prostate, colon, rectum, or lung, we were able to detect between one and 6.8 x 10(4) cytokeratin-expressing tumor cells in 21 of 34 patients. This corresponds to frequencies of tumor cells between 6.8 x 10(-9) and 1.1 x 10(-3) among nucleated cells in the original sample. Enriched tumor cells were further analyzed for expression of tissue-specific and prognostic markers such as breast mucin glycoproteins, erbB2, and CD44v6 for additional characterization and to confirm their tumor origin. The technique described could become a valuable tool for the quantification and molecular characterization of metastatic carcinoma cells in hematopoietic tissue, and may ultimately prove useful in the diagnosis, prognosis, and monitoring of patients with carcinoma.


Electric-field-induced redox potential shifts of tetraheme cytochromes c3 immobilized on self-assembled monolayers: surface-enhanced resonance Raman spectroscopy and simulation studies.
The tetraheme protein cytochrome c(3) (Cyt-c(3)) from Desulfovibrio gigas, immobilized on a self-assembled monolayer (SAM) of 11-mercaptoundecanoic acid, is studied by theoretical and spectroscopic methods. Molecular dynamics simulations indicate that the protein docks to the negatively charged SAM via its lysine-rich domain around the exposed heme IV. Complex formation is associated with only little protein structural perturbations. This finding is in line with the resonance Raman and surface-enhanced resonance Raman (SERR) spectroscopic results that indicate essentially the same heme pocket structures for the protein in solution and adsorbed on SAM-coated Ag electrodes. Electron- and proton-binding equilibrium calculations reveal substantial negative shifts of the redox potentials compared to the protein in solution. The magnitude of these shifts decreases in the order heme IV (-161 mV) > heme III (-73 mV) > heme II (-57 mV) > heme I (-26 mV), resulting in a change of the order of reduction. These shifts originate from the distance-dependent electrostatic interactions between the SAM headgroups and the individual hemes, leading to a stabilization of the oxidized forms. The results of the potential-dependent SERR spectroscopic analyses are consistent with the theoretical predictions and afford redox potential shifts of -160 mV (heme IV), -90 mV (heme III), -70 mV (heme II), and +20 mV (heme I) relative to the experimental redox potentials for Cyt-c(3) in solution. SERR spectroscopic experiments reveal electric-field-induced changes of the redox potentials also for the structurally very similar Cyt-c(3) from Desulfovibrio vulgaris, although the shifts are somewhat smaller compared to Cyt-c(3) from D. gigas. This study suggests that electric-field-induced redox potential shifts may also occur upon binding to biomembranes or partner proteins and thus may affect biological electron transfer processes.


[Endometrial polyps. A clinico-pathologic analysis].
A clinico-pathologic analysis of 92 cases of endometrial polyps was carried out and the endometrium adjacent to the polyps was studied in 69 cases. Most endometrial polyps occurred between 30-60 years of age, often accompanied by abnormal uterine bleeding. Immature endometrial polyp was the most common pathologic type (65.0%), usually associated to some extent with hyperplastic changes. Cystic glandular hyperplasia was observed in nearly half of the polyps obtained from postmenopausal patients. Different histologic pictures were found in the adjacent endometrial tissues, of which 59.4% showed normal changes.


Prevalence of depressive symptoms in primary school students in China: A systematic review and meta-analysis.
Depression in children and adolescents is usually under-recognized. The findings of epidemiological studies on depressive symptoms in primary school students are inconsistent across studies. This study reports a systematic review and meta-analysis on the prevalence of depressive symptoms in primary school students in China. Literature search was performed in both international (PubMed, PsycINFO, EMBASE) and Chinese (China National Knowledge Internet, WANFANG Data and Chinese Biological Medical Literature) databases. The random-effects model was used to analyze data. Twenty-seven studies involving 42,374 subjects were included. The pooled prevalence of depressive symptoms in Chinese primary school students was 17.2% (95% CI: 14.3%-20.5%). Subgroup analyses found that the prevalence significantly varied between geographic regions, with western China reporting the highest prevalence. Meta-regression analyses found that year of survey and study quality were significantly associated with the prevalence of depressive symptoms. Given the high prevalence of depressive symptoms and its negative health outcomes, preventive measures, regular screening and effective treatments need to be implemented for this population.


Reperfusion therapy in ST-elevation myocardial infarction: guidelines, strategies, pharmacology, and stent selection.
Treatment of acute ST-elevation myocardial infarction (STEMI) has rapidly evolved with many advances made in the past decade. Percutaneous coronary intervention is the preferred strategy when available, although there remains a role for thrombolytic therapy, with prompt reperfusion as the primary goal. With regards to antithrombotic therapy, bivalirudin now has a significant role in STEMI care with improved outcomes over unfractionated heparin plus GP IIb/IIIa inhibitors. Dual antiplatelet therapy has become a mainstay of treatment with combination of aspirin and clopidogrel, as well as an expanding role of more potent novel agents, prasugrel and ticagrelor. In primary PCI in STEMI, coronary stents are now being used routinely, although short-term and long-term outcomes of drug-eluting stents (DES) versus bare metal stents (BMS) continue to be studied. Recent meta-analyses have examined the trade-off of lower rates of in-stent restenosis and need for target vessel revascularization with DES versus the potential increase in the risk of stent thrombosis and need for longer course of dual antiplatelet therapy. This review will discuss the current STEMI guidelines and strategies, recent advances in pharmacotherapy, and data on stent selection.


Involvement of UCP3 in mild uncoupling and lipotoxicity.
Although vital to life, mitochondria are also the major source of ROS production, which may have unwanted detrimental effects on DNA, RNA and protein structures Therefore, mitochondria must exhibit well-developed mechanisms to regulate its ROS production. One such mechanism might be mild uncoupling of the mitochondrial respiratory chain, thereby lowering the proton gradient across the inner mitochondrial membrane and directly lowering ROS production. Mitochondrial uncoupling proteins have been shown to possess mild uncoupling activity and may therefore be important regulator of mitochondrial ROS production. The skeletal muscle isoform of the uncoupling protein family, UCP3, seems to be specifically active under conditions of high fatty acid availability. Although the exact function of UCP3 is not yet unravelled, UCP3 is activated by lipid peroxides and suggested to export fatty acid anions and/or peroxides from the mitochondrial matrix, thereby specifically protecting fatty acids from ROS-induced oxidative damage. Protein levels of UCP3 are reduced with aging and in the (pre)-diabetic state, both conditions characterized by increased levels of oxidative damage to lipids and proteins and reduced mitochondrial function. Whether UCP3 is causally related to mitochondrial dysfunction and is essential in the prevention and treatment of lipid-induced mitochondrial dysfunction requires further study.


[Isolated jejunal grafting in surgery of esophageal carcinoma].
Six cases of either esophageal carcinoma or its post resection complications were treated by isolated jejunal grafting in our department in recent two years. Of the six cases, there were 2 of cervical anastomotic leakage after esophagocolostomy, 1 each of cervical anastomotic leakage after esophago-gastrostomy, cervical esophageal carcinoma, cervical anastomotic stricture after esophagogastrostomy, and defect of esophagus. Good results had been achieved in all of the six cases. Not a single death occurred. Indications for the use of isolated jejunal grafting and the operative techniques were discussed in detail. The author concludes that isolated jejunal grafting is worth recommending.


Fluorescent signaling based on sulfoxide profluorophores: application to the visual detection of the explosive TATP.
The first visual fluorescence-based assay for the peroxide explosive triacetone triperoxide (TATP) is described. The assay is based on a conceptually new fluorescence signaling mechanism, in which nonemissive pyrenyl sulfoxide profluorophores are oxidized to visibly emissive pyrenyl sulfones. Although not without limitations, these first-generation fluorescent probes can provide a visual response to ca. 100 nmol of TATP. In addition, the success of this assay suggests the potential for broader application of aryl sulfoxides in fluorescent chemosensing.


Turning the tables: when the student teaches the professional -- a case description of an innovative teaching approach as told by the students.
Is it possible to increase the value, meaningfulness, and relevance of a course experience by integrating it with the healthcare context? Students and teachers from a course on organization, learning and leadership sought to explore this possibility through a collaborative effort with nurses from an affiliated teaching hospital. Working as teachers, students created continuing nursing education (CNE) courses using the Adaptive Reflection process. The students and teachers then researched the experience in terms of: 1) content analysis of student self-reflections (discussion notes and logbooks) on the learning process, 2) a student self-assessed outcome achievement survey, and 3) perceived relevance of the CNE courses by the clinical nurse educators. Thirteen nursing students created three CNE courses together with sixteen nurses. Each course consisted of multiple 20-minute long web-based modules with automatic formative feedback. In the process, students exceeded course outcome-levels, journeyed from chaos to confidence and experienced new ways of viewing the group and their own capabilities. The innovative design of the course moved the focus from student-centered learning to learning by contributing to health care. Working in a real world context, the content of the students' efforts and the skills they developed not only met course requirements, but were also aligned with the needs of the wards. This contribution was valued by the students and the RNs which enhanced students' feelings of self-confidence. Further research lies in testing the model in other contexts.


Coverage of the English national human papillomavirus (HPV) immunisation programme among 12 to 17 year-old females by area-level deprivation score, England, 2008 to 2011.
The English national human papillomavirus (HPV) immunisation programme has offered vaccination to girls aged 12 years at the start of each school year since September 2008. A catch-up programme has offered vaccination to girls up to 18 years. Delivery is predominantly school-based, with some general practitioner (GP)-based immunisation. The relationship between HPV immunisation coverage and deprivation (index of multiple deprivation, IMD) was assessed by geographical area (N=151) for each school year offered the HPV vaccine between 2008 to 2011 using the Spearman's rank correlation coefficient, and compared to that for adequate cervical screening of women aged 25 to 49 years. Coverage at age 12 showed no significant association with IMD at the area-level (p=0.12). Within the catch-up years, there was some suggestion of higher deprivation being associated with lower coverage. This was not significant for girls offered immunisation under 16 years (in compulsory education) (p=0.09), but was more marked and statistically significant for older girls (p<0.0001). The proportion of women aged 25 to 49 years with an adequate cervical screen was negatively associated with deprivation (p<0.0001). School-based HPV immunisation delivery appears to be successfully reducing inequalities in cervical cancer control at area-level. However, the catch-up cohorts above the age of compulsory education may face increased inequality. Further investigation is needed into individual-level factors associated with coverage.


Common Secondary Genomic Variants Associated With Advanced Epithelioid Hemangioendothelioma.
Epithelioid hemangioendothelioma (EHE) is a rare, malignant vascular sarcoma characterized in most cases by a WWTR1-CAMTA1 fusion. The clinical course of EHE exhibits a dual nature. The condition is often indolent but can rapidly grow and metastasize unpredictably. No biomarkers to date are available to predict this phenotype. The hypothesis of this study was that better defining the genomic landscape of EHE using next-generation sequencing could offer additional therapies and insight into clinical outcomes. To characterize secondary EHE genomic alterations and their association with clinical outcomes. Multicenter, cross-sectional, retrospective study of next-generation sequencing results collected from participants diagnosed with EHE. Data were abstracted between May 1, 2013, and May 31, 2019. This analysis was conducted from January through June 2019. Summary genomic data were provided by commercial genomic testing companies. Presence or absence of secondary pathogenic genomic variants and their association with disease stage and clinical features. A total of 49 participants with EHE were assessed for the presence or absence of secondary genomic variants. Of these, 32 (65.3%) were female; the mean (SD) age at diagnosis was 49.9 (18.3) years (range, 11-81 years). In all, 46 participants (93.9%) had confirmed WWTR1-CAMTA1 fusion; 26 participants (57.1%) exhibited a pathogenic genomic variant secondary to the WWTR1-CAMTA1 fusion; and 9 participants (18.4%) exhibited potentially targetable genomic variants. Commonly altered genes included CDKN2A/B, RB1, APC, and FANCA. Participants older than 45 years at diagnosis had an increased prevalence of secondary genomic variants that was not statistically significant (65.6% vs 38.5%; difference, 27.1%; 95% CI, -3.5% to 58.0%; P = .16) and were more likely to have a clinically targetable variant (28.1% vs 0%; difference, 28.1%; 95% CI, 11.2%-40.2%; P = .03). In 14 participants with clinical data available, those with stage III/IV EHE were more likely to exhibit a secondary pathogenic genomic variant (80% vs 0%; difference, 80%; 95% CI, 55.2%-100%; P = .006). Participants with stage III/IV EHE were diagnosed at an older age (mean [SD] age, 54.6 [14.1] years vs 31.7 [16.0] years; P = .05) and had elevated WWTR1-CAMTA1 fusion expression that was not statistically significant (mean [SD] expression, 677 [706] copies vs 231 [213] copies; P = .20). Although EHE exhibits few secondary genomic variants, presence of key secondary variants may be prognostic for aggressive EHE. Further research is needed to confirm this finding and determine whether more intensive upfront treatment is necessary for these patients.


Genetic Diversity of Eight Domestic Goat Populations Raised in Turkey.
The objective of this study was to determine the intra- and intergenetic diversities of eight different goat populations in Turkey including Hair, Angora, Kilis, Yayladag, Shami, Honamli, Saanen, and Alpine. A total of 244 DNA samples were genotyped using 11 microsatellites loci. The genetic differentiation between breeds was considerable as a result of the statistically significant (P < 0.001) pairwise F ST values of each pair of breeds. Exceptionally, F ST values calculated for Honamli and Hair breeds were statistically nonsignificant (P > 0.05). Heterozygosity values ranged between 0.62 and 0.73. According to the structure and assignment test, Angora and Yayladag goats were assigned to the breed they belong to, while other breeds were assigned to two or more different groups. Because this study for the first time presented genetic data on the Yayladag goat, results of structure analysis and assigned test suggest that further analyses are needed using additional and different molecular markers.


Occupational accidents in artisanal mining in Katanga, D.R.C.
This study focuses on accidents in artisanal mining, to support policies improving miners' employability. Based on a questionnaire administered in November 2009 to a sample of 180 miners from the artisanal mining of LUPOTO, in the Province of Katanga, we explored significant trends between the accidents and their consequences and behavioral or sociological variables. During the 12 months preceding the study, 392 accidents occurred, affecting 72.2% of miners. Tools handling represents 51.5%, of the accidents' causes, followed by handling heavy loads (32.9%). Factors such as age, seniority or apprenticeship did not generate significant differences. Contusions were the most common injuries (50.2%), followed by wounds (44.4%). These injuries were located in upper limbs (50.5%) and in lower limbs (29.3%). 80.5% of miners were cared for by their colleagues and 50% of them could not work for more than 3 days. Physical sequelae were reported by 19% of the injured miners. Many surveys related to accidents in the area of artisanal mining report such high frequency. The unsuitability of tools to jobs to be done is usually raised as one of the major causes of accidents. The lack of differentiation of the tasks carried out in relation to age is another factor explaining the lack of protective effect of seniority as it minimizes the contribution of experience in the worker's safety. The apprenticeship reported is inadequate; it is rather a learning by doing than anything else. That is why it lacks protective effect. Low income combined with precariousness of artisanal mining are likely to explain the low level of work stoppages. Tools improvement associated with adequate training seem to be the basis of accident prevention. Availability of suitable medical care should improve artisanal miners' recovery after accidents.


Integration of Latino/a cultural values into palliative health care: a culture centered model.
Culture helps us grapple with, understand, and navigate the dying process. Although often overlooked, cultural values play a critical and influential role in palliative care. The purpose of the present study was two-fold: one, to review whether Latino/a cultural values have been integrated into the palliative care literature for Latinos/as; two, identify publications that provide recommendations on how palliative care providers can integrate Latino/a cultural values into the end-of-life care. A comprehensive systematic review on the area of Latino/a cultural values in palliative care was conducted via an electronic literature search of publications between 1930-2013. Five articles were identified for reviewing, discussing, or mentioning Latino/a cultural values and palliative care. Only one article specifically addressed Latino/a cultural values in palliative care. The four remaining articles discuss or mention cultural values; however, the cultural values were not the main focus of each article's thesis. The results of the current study highlight the lack of literature specifically addressing the importance of integrating Latino/a cultural values into the delivery of palliative care. As a result, this article introduces the Culture-Centered Palliative Care Model (CCPC). The article defines five key traditional Latino/a cultural values (i.e., familismo, personalismo, respeto, confianza, and dignidad), discusses the influence of each value on palliative health care, and ends with practical recommendations for service providers. Special attention is given to the stages of acculturation and ethnic identity.


A Candida albicans PeptideAtlas.
Candida albicans public proteomic datasets, though growing steadily in the last few years, still have a very limited presence in online repositories. We report here the creation of a C. albicans PeptideAtlas comprising near 22,000 distinct peptides at a 0.24% False Discovery Rate (FDR) that account for over 2500 canonical proteins at a 1.2% FDR. Based on data from 16 experiments, we attained coverage of 41% of the C. albicans open reading frame sequences (ORFs) in the database used for the searches. This PeptideAtlas provides several useful features, including comprehensive protein and peptide-centered search capabilities and visualization tools that establish a solid basis for the study of basic biological mechanisms key to virulence and pathogenesis such as dimorphism, adherence, and apoptosis. Further, it is a valuable resource for the selection of candidate proteotypic peptides for targeted proteomic experiments via Selected Reaction Monitoring (SRM) or SWATH-MS. This C. albicans PeptideAtlas resolves the previous absence of fungal pathogens in the PeptideAtlas project. It represents the most extensive characterization of the proteome of this fungus that exists up to the current date, including evidence for uncharacterized ORFs. Through its web interface, PeptideAtlas supports the study of interesting proteins related to basic biological mechanisms key to virulence such as apoptosis, dimorphism and adherence. It also provides a valuable resource to select candidate proteotypic peptides for future (SRM) targeted proteomic experiments. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.


Partner support and pregnancy wantedness.
Women who experience unwanted pregnancy are at a greater risk of complicated pregnancy outcomes, and their children are more likely to experience physical or psychological problems in infancy, than those women with wanted pregnancies. The objective of this research was to explain the impact of a partner on women's decisions to want or not want their pregnancies. A primary study subsample of 349 clinical interviews of pregnant women comprised the quantitative portion of the analysis, with a secondary study subsample of 20 in-depth qualitative interviews of pregnant women complementing the statistical findings. Both samples included adult women (at least age 20 yr) of different ethnic groups who received Medicaid for their pregnancies and were in their first or early second trimester of pregnancy. Chi-square, t tests, and logistic regression were used for statistical analyses. A partner's stability, status, feelings toward pregnancy, and level of dependability and support all had a significant influence on women's experiences of unwanted pregnancy. Variables including use of contraception (OR = 3.3), women's ethnicity (OR = 1.9), partner's feelings about pregnancy (OR = 2.0), amount of social support (OR = 1.2), and mother's instrumental support (OR = 0.85) all affected women's perceptions of wanting the pregnancy. These results were used to create a model of unwanted pregnancy, beginning before conception and ending with either termination of pregnancy or initiation of prenatal care. The support and concern of a partner during pregnancy can have positive consequences for a mother's desire to carry out the pregnancy. To increase their commitment to the pregnancy and childbirth, partners should be included more in the prenatal care process.


Phytochemical Analysis and Evaluation of Genotoxic, Antigenotoxic Effects in Bacterial Models, and Hypoglycemic Activity of Epilobium angustifolium L. with Bioguided Isolation of Active Compounds.
This study examined the effects of methanol extract and its sub-extracts from Epilobium angustifolium on α-glucosidase and α-amylase activity. Secondary metabolites and amino acids were quantified using LC-MS/MS. Dichloromethane sub-extract displayed the highest activity and was chosen for further investigation. Despite the widespread use of E. angustifolium, genotoxicity studies were conducted to assess its safety. Dichloromethane significantly inhibited α-glucosidase (IC50 =17.340 μg/mL), making it approximately 293 times more effective than acarbose. Six known compounds, including gallic acid (1), a mixture of quercetin-3-O-α-galactoside (2a) and quercetin-3-O-α-glucoside (2b), quercetin-3-O-α-glucuronic acid (3), quercetin-3-O-α-rhamnoside (4), and kaempferol-3-O-α-rhamnoside (5) were identified. Quercetin-3-O-α-rhamnoside exhibited the highest inhibition of α-glucosidase (IC50 =1735±85 μM), making it 3.70 times more effective than acarbose. Dichloromethane also showed significant antigenotoxic activity against mutagenesis induced by NaN3, 9-AA, 4-NPD, and MNNG. Gallic acid was found in the highest abundance (13253.6931 ng/mL) in the methanolic extract. Furthermore, L-Aspartic acid was the most concentrated amino acid (363.5620 nmol/mL) in the methanolic extract.


Development of microsatellite markers for Hoplias malabaricus (Erythrinidae).
We identified 14 microsatellite loci for the wolf fish, Hoplias malabaricus (Erythrinidae), from a genomic shotgun library. Twenty-five primers were designed, and 48 individuals of H. malabaricus from four localities of northwest Goiás, in central Brazil, were genotyped to characterize the polymorphism at each locus. Fourteen primers amplified clearly interpretable products using a single PCR protocol; six loci were polymorphic, but with a low number of alleles per locus (2 or 3). Expected heterozygosities for polymorphic loci ranged from 0.136 to 0.505. Combined paternity exclusion probability (0.638) was low and combined genetic identity (0.056) was high in studies of parentage. The low polymorphism may be due to the small microsatellite size and the large size of the motifs.


Exhaled breath condensate-site and mechanisms of formation.
Exhaled breath condensate (EBC) analysis is a promising tool for diagnosis and management of pulmonary diseases. Its clinical usefulness is still limited however due to unresolved issues around e.g. reproducibility, anatomical site of origin of EBC solutes and mechanisms of EBC formation. To gain some knowledge on these issues, three different airway deposition patterns of an aqueous aerosol containing technetium-99m were studied in eight healthy non-smoking subjects. EBC was collected 20 min after each radioaerosol administration and analyzed for gamma radiation and electrolytes. Radioaerosol deposition in preferentially central lung compared with preferentially peripheral lung resulted in 3.8 times higher EBC radioactivity. EBC concentrations of Na(+) and K(+) correlated significantly indicating dilution by water vapor to be a major source of variability. Since Na(+)/K(+)- and Na(+)/S(2-)-concentration ratios, but not Na(+)/Cl(-)- or Na(+)/Ca(2+)-, were comparable to those previously reported for alveolar lining fluid (ALF), some mechanisms other than dilution are likely also to be involved. In conclusion, our findings indicate that EBC derives mainly from the central airways, that the electrolyte composition of EBC does not consistently reflect that of ALF, and that EBC concentrations of electrolytes are determined not only by ALF dilution with water vapor but also by other mechanisms.


The chemistry and enzymology of the type I signal peptidases.
The discovery that proteins exported from the cytoplasm are typically synthesized as larger precursors with cleavable signal peptides has focused interest on the peptidases that remove the signal peptides. Here, we review the membrane-bound peptidases dedicated to the processing of protein precursors that are found in the plasma membrane of prokaryotes and the endoplasmic reticulum, the mitochondrial inner membrane, and the chloroplast thylakoidal membrane of eukaryotes. These peptidases are termed type I signal (or leader) peptidases. They share the unusual feature of being resistant to the general inhibitors of the four well-characterized peptidase classes. The eukaryotic and prokaryotic signal peptidases appear to belong to a single peptidase family. This review emphasizes the evolutionary concepts, current knowledge of the catalytic mechanism, and substrate specificity requirements of the signal peptidases.


Power production and microbial community composition in thermophilic acetate-fed up-flow and flow-through microbial fuel cells.
The microbial communities developed from a mixed-species culture in up-flow and flow-through configurations of thermophilic (55 °C) microbial fuel cells (MFCs), and their power production from acetate, were investigated. The up-flow MFC was operated for 202 days, obtaining an average power density of 0.13 W/m3, and Tepidiphilus was the dominant transcriptionally-active microorganisms. The planktonic community developed in the up-flow MFC was used to inoculate a flow-through MFC resulting in the proliferation of Ureibacillus, whose relative abundance increased from 1 to 61% after 45 days. Despite the differences between the up-flow and flow-through MFCs, including the anode electrode, hydrodynamic conditions, and the predominant microorganism, similar (p = 0.05) volumetric power (0.11-0.13 W/m3), coulombic efficiency (16-18%) and acetate consumption rates (55-69 mg/L/d) were obtained from both. This suggests that though MFC design can shape the active component of the thermophilic microbial community, the consortia are resilient and can maintain similar performance in different MFC configurations.


Dose-dependence of PTH-related peptide-1 on the osteogenic induction of MC3T3-E1 cells in vitro.
Parathyroid hormone (PTH), an 84-amino acid peptide, is an endocrine hormone that is secreted by parathyroid glands. PTH performs important functions in calcium regulation and bone remodeling. The PTH (1-34) named teriparatide, a 34-amino acid peptide derived from the N-terminus of PTH, conserves most of the functions of PTH, specifically the osteogenic capability. However, teriparatide is only used by injection and exhibits short duration. In addition, this PTH could not thoroughly expose active sites. In this study, a novel PTH-related peptide (designated PTHrP-1) derived from the N-terminus of PTH was added into the complete medium at different concentrations of PTHrP-1 (0, 50, 100, and 200 ng/mL) to induce the MC3T3-E1 cells. PTHrP-1 was detected by high-performance liquid chromatography and matrix-assisted laser desorption/ionization-time-of-flight mass spectroscopy. Cell morphology, cell proliferation, alkaline phosphatase (ALP), and ALP activity, osteocalcin concentration, and collagen type I (Col-I), osteopontin (OPN), and osteocalcin (OCN) mRNA expression by RT-PCR and protein expression by western blotting were observed and detected. The purity of the PTHrP-1 was 95.14%, and the PTHrP-1 can induce MC3T3-E1 cells into osteoblasts, thus improving ALP activity and OCN concentration, and increasing Col-I, OPN, and OCN mRNA expression and protein expression in MC3T3-E1 cell cultures. The PTHrP-1 proved to be an ideal active peptide. In addition, the osteogenic ability of PTHrP-1 at 200 and 100 ng/mL concentrations was not significantly different but significantly higher than 50 and 0 ng/mL groups. Results indicate that PTHrP-1 is a kind of active peptides that exhibits good biocompatibility with MC3T3-E1 cells and could improve cell proliferation and osteogenic differentiation. Moreover, PTHrP-1, at the preferable concentration of 100 ng/mL, could effectively promote MC3T3-E1 cells into osteoblasts.


Prevalence of Advanced Parkinson's Disease in Patients Treated in the Hospitals of the Spanish National Healthcare System: The PARADISE Study.
Advanced Parkinson's disease (APD) has been recently defined as a stage in which certain symptoms and complications are present, with a detrimental influence on the overall patient's health conditions and with a poor response to conventional treatments. However, historically, the term APD has been controversial, thus consequently, APD prevalence has not been previously studied. The main objective was to determine the prevalence of APD in patients diagnosed with idiopathic PD in hospitals of the Spanish National Healthcare System. Secondary objectives were the prevalence and incidence of PD and the clinical and sociodemographic characteristics and quality of life of patients with APD or non-APD. This was a non-interventional, cross-sectional, multicenter, national study in the hospital setting. The study population included 929 patients with PD (mean age 71.8 ± 10.1 years; 53.8% male) and a mean time since diagnosis of 6.6 ± 5.4 years. At the time of diagnosis, 613 patients (66.06%) reported having had premotor symptoms. The Hoehn and Yahr stage was 1 in 15.7% of the patients, 2 in 42.8%, 3 in 30.1%, 4 in 9.9%, and 5 in 1.4%; 46.9% of the patients had comorbidities (mean age-adjusted Charlson comorbidity index 3.5 ± 1.7; median 10-year survival 77%) and the mean 8-item Parkinson's Disease Quality of Life Questionnaire was 27.8 ± 20.5. We found an APD prevalence of 38.21% (95%CI: 35.08-41.42%), a PD prevalence of 118.4 (95%CI: 117.3-119.6), and a PD incidence of 9.4 (95%CI: 5.42-13.4) all per 100,000 population. Among the APD population, a 15.2% were receiving some form of therapy for advanced stages of the disease (deep brain stimulation, levodopa/carbidopa intestinal gel, or apomorphine subcutaneous infusion). The percentage of patients with APD in the hospitals of the Spanish National Healthcare System was 38.2%.


Missense mutations in SARS-CoV2 genomes from Indian patients.
The genetic diversity of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) in several countries sums up to worldwide genetic diversity. In this present study, variations in terms of missense mutations among the SARS-CoV2 genomes from 128 Indian patients, as of May 2020, are accounted and thereby some key findings with some hypotheses were made. These mutations across various genes of these genomes show wide genetic variations in sequence and rapid evolution of SARS-CoV2 virus. The presence of unique mutations in the studied SARS-CoV2 genomes may led to their attenuation. Few Genes such as ORF6, ORF10 are free from any mutations in the Indian context of 339 genomes observed as of 14th July 2020. Further, E protein contains only one mutation. This may suggest that designing a therapeutic approach against ORF6, ORF10 and E genes may have a beneficial effect in controlling COVID-19 pandemic especially in India.


Potential effect of climate change on malaria transmission in Africa.
Climate change is likely to affect transmission of vector-borne diseases such as malaria. We quantitatively estimated current malaria exposure and assessed the potential effect of projected climate scenarios on malaria transmission. We produced a spatiotemporally validated (against 3791 parasite surveys) model of Plasmodium falciparum malaria transmission in Africa. Using different climate scenarios from the Hadley Centre global climate model (HAD CM3) climate experiments, we projected the potential effect of climate change on transmission patterns. Our model showed sensitivity and specificity of 63% and 96%, respectively (within 1 month temporal accuracy), when compared with the parasite surveys. We estimate that on average there are 3.1 billion person-months of exposure (445 million people exposed) in Africa per year. The projected scenarios would estimate a 5-7% potential increase (mainly altitudinal) in malaria distribution with surprisingly little increase in the latitudinal extents of the disease by 2100. Of the overall potential increase (although transmission will decrease in some countries) of 16-28% in person-months of exposure (assuming a constant population), a large proportion will be seen in areas of existing transmission. The effect of projected climate change indicates that a prolonged transmission season is as important as geographical expansion in correct assessment of the effect of changes in transmission patterns. Our model constitutes a valid baseline against which climate scenarios can be assessed and interventions planned.


Harvesting autologous stem cells from a patient with red blood cell abnormalities of β-thalassemia intermedia.
Autologous stem cell transplants in patients with hemoglobinopathies are limited. Previous reports used granulocyte-colony-stimulating factor (G-CSF) for mobilization of stem cells; there are no reported cases undergoing plerixafor mobilization. We report such a patient, providing guidance for peripheral blood stem cells collection when aberrant red blood cells (RBCs) disrupt normal separation. A patient with β-thalassemia intermedia and hereditary persistence of fetal hemoglobin presented for peripheral blood stem cell collection for autologous transplant for myeloma. He underwent splenectomy for anemia secondary to hemoglobinopathy and chemotherapy, ceasing RBC transfusions. The patient was mobilized using plerixafor after collection with G-CSF failed. Collections were performed using an apheresis system, processing 24 L daily. Peripheral blood and apheresis product CD34 determinations were performed daily. On Day 1, the product yield was 0.04 × 10(6) CD34 cells/kg, less than expected based on white blood cell count and CD34-positive cells. Peripheral blood smear showed nucleated RBCs and RBC morphologic abnormalities. Changes in instrument variables were made after consultation with Terumo BCT to adjust for variable distribution of mononuclear and stem cells during centrifugation. Collecting stem cells at a deeper location and centrifuging faster improved collection, and a cumulative total of 4.40 × 10(6) CD34 cells/kg was achieved after four collections. The patient underwent tandem autologous transplantation and engrafted within 12 to 13 days of each transplant. Adjustments in apheresis variables allowed successful collection of peripheral blood stem cells from a patient with RBC anomalies of β-thalassemia that interfered with standard stem cell harvesting.


The cis-regulatory logic of the mammalian photoreceptor transcriptional network.
The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs) mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation.


Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo.
Expression of latent membrane protein 2 (LMP2A) during B-cell development leads to global alterations in gene transcription similar to those seen in Hodgkin Reed-Sternberg cells of Hodgkin lymphoma (HL). Along with the consistent detection of LMP2A in Epstein-Barr virus-associated HL, this implicates a role for LMP2A in the pathogenesis of HL. We have shown that LMP2A constitutively activates the Notch1 pathway to autoregulate the LMP2A promoter. To determine whether constitutive activation of the Notch pathway is important for LMP2A-mediated alterations in B-cell development in vivo, TgE-LMP2A-transgenic mice were intercrossed with mice expressing loxP-flanked Notch1 genes and Cre recombinase. B cells from TgE Notch1(lox/lox)-CD19(+/Cre) mice have an increase in immunoglobulin M and CD43 and a decrease in CD5 expression in the bone marrow compared with TgE Notch1(lox/lox) mice, indicating the LMP2A signal for developmental aberrations is impaired in the absence of Notch1. Real-time reverse-transcribed polymerase chain reaction analysis reveals that LMP2A requires the Notch1 pathway to alter levels of B cell-specific transcription factors, E2A and EBF. Interestingly, Notch1 appears to be important for LMP2A-mediated survival in low interleukin-7. We propose that LMP2A and the Notch1 pathway may cooperate to induce the alterations in B-cell identity seen in Hodgkin Reed-Sternberg cells.


[Comparative study of the effectiveness of Cozaar monotherapy and Cozaar and melatonin combined therapy in aged patients with hypertension].
Effectiveness of Cozaar monotherapy (50 mg at 8 a.m.) was compared to that of Cozaar combination with melatonin (3 mg before sleep) in 21 patients with hypertension stage II (mean age 62 years). Clinical symptoms and hemodynamic parameters were evaluated with ECG and blood pressure monitoring. The findings were processed with statistical methods and Kosinor-analysis. Cozaar alone had moderate hypotensive and vasodilating effects, affected circadian rhythm of systolic and diastolic blood pressure, heart rate. Combination Cozaar + melatonin reduced blood pressure more noticeably, diminished cardiac output, energy consumption of the myocardium, normalized normal chronostructure of blood pressure and heart rate circadian rhythms.


A PBP 2 mutant devoid of the transpeptidase domain abolishes spermine-β-lactam synergy in Staphylococcus aureus Mu50.
Exogenous spermine was reported to enhance the killing of methicillin-resistant Staphylococcus aureus (MRSA) by β-lactams through a strong synergistic effect of unknown nature. Spermine alone also exerts an antimicrobial activity against S. aureus in a pH-dependent manner. MIC measurements revealed stronger effects of spermine under alkaline conditions, suggesting the nucleophilic property of spermine instead of its positive charge as the cause of adverse effects. A spontaneous suppressor mutant (MuM) of MRSA Mu50 was selected for spermine resistance and conferred complete abolishment of spermine-β-lactam synergy. In comparison to that in Mu50, the spermine MIC in MuM remained constant (64 mM) at pH 6 to 8; however, MuM, a heat-sensitive mutant, also grew in a very narrow pH range. Furthermore, MuM acquired a unique phenotype of vancomycin-spermine synergy. Genome resequencing revealed a 7-bp deletion in pbpB, which results in a truncated penicillin-binding protein 2 (PBP 2) without the transpeptidase domain at the C terminus while the N-terminal transglycosidase domain remains intact. The results of fluorescent Bocillin labeling experiments confirmed the presence of this defective PBP 2 in MuM. All the aforementioned phenotypes of MuM were reverted to those of Mu50 after complementation by the wild-type pbpB carried on a recombinant plasmid. The anticipated changes in cell wall metabolism and composition in MuM were evidenced by observations that the cell wall of MuM was more susceptible to enzyme hydrolysis and that MuM exhibited a lower level of autolytic activities. Pleiotropic alterations in gene expression were revealed by microarray analysis, suggesting a remarkable flexibility of MuM to circumvent cell wall damage by triggering adaptations that are complex but completely different from that of the cell wall stress stimulon. In summary, these results reveal phenotypic changes and transcriptome adaptations in a unique pbpB mutant and provide evidence to support the idea that exogenous spermine may perturb normal cell wall formation through its interactions with PBP 2.


The Decremental Protocol as an Alternative Protocol to Measure Maximal Oxygen Consumption in Athletes.
To determine whether a decremental protocol could elicit a higher maximal oxygen consumption (VO2max) than an incremental protocol in trained participants. A secondary aim was to examine whether cardiac-output (Q) and stroke-volume (SV) responses differed between decremental and incremental protocols in this sample. Nineteen runners/triathletes were randomized to either the decremental or incremental group. All participants completed an initial incremental VO2max test on a treadmill, followed by a verification phase. The incremental group completed 2 further incremental tests. The decremental group completed a second VO2max test using the decremental protocol, based on their verification phase. The decremental group then completed a final incremental test. During each test, VO2, ventilation, and heart rate were measured, and cardiac variables were estimated with thoracic bioimpedance. Repeated-measures analysis of variance was conducted with an alpha level set at .05. There were no significant main effects for group (P = .37) or interaction (P = .10) over time (P = .45). VO2max was similar between the incremental (57.29 ± 8.94 mL · kg-1 · min-1) and decremental (60.82 ± 8.49 mL · kg-1 · min-1) groups over time. Furthermore, Q and SV were similar between the incremental (Q 22.72 ± 5.85 L/min, SV 119.64 ± 33.02 mL/beat) and decremental groups (Q 20.36 ± 4.59 L/min, SV 109.03 ± 24.27 mL/beat) across all 3 trials. The findings suggest that the decremental protocol does not elicit higher VO2max than an incremental protocol but may be used as an alternative protocol to measure VO2max in runners and triathletes.


Pharmacokinetics of [14C]methylglyoxal-bis-guanylhydrazone) in patients with leukemia.
Methylglyoxal-bis(guanylhydrazone) (MGBG; NSC 32946), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase (EC 126.96.36.199), currently being reevaluated for its clinical antileukemic activity. MGBG labeled with 14C in the guanylhydrazone moiety was administered i.v. (150 microCi; specific activity, 1.9 microCi/mumol; 20 mg total) to six patients with leukemia. All patients in the study had normal renal and hepatic function. [14C]MGBG underwent no in vivo metabolism; it disappeared from the plasma with an average terminal t 1/2 of 4.1 hr. The 72-hr cumulative urinary excretion was only 14.5 +/- 2.2% (S.E.M.) of the total radioactive dose. The apparent volume of distribution was 661 ml/kg and the total clearance rate was 21.2 ml/kg/min. The low urinary excretion rate and the relatively rapid plasma clearance suggest that MGBG may be sequestered in the body. Therefore, if MGBG is administered by a frequent treatment schedule, the prolonged biological half-life in humans may significantly contribute to its clinical toxicity.


ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain.
SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme's catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers. Chemical crosslinking studies show that SMSr self-associates into ER-resident trimers and hexamers that resemble the helical oligomers formed by DGKδ-SAM. Residues critical for DGKδ-SAM oligomerization are conserved in SMSr-SAM and their substitution causes a dissociation of SMSr oligomers as well as a partial redistribution of the enzyme to the Golgi. Conversely, treatment of cells with curcumin, a drug disrupting ceramide and Ca2+ homeostasis in the ER, stabilizes SMSr oligomers and promotes retention of the enzyme in the ER. Our data provide first demonstration of a multi-pass membrane protein that undergoes homotypic oligomerization via its SAM domain and indicate that SAM-mediated self-assembly of SMSr is required for efficient retention of the enzyme in the ER.


Understanding extreme mortality among prisoners: a national cohort study in Scotland using data linkage.
Mortality is known to be extremely high among people who have been imprisoned, but there is limited information about the factors that explain this increased risk. Standard record linkage methods were used to link Scottish prison records and mortality data for all individuals imprisoned in Scotland for the first time between 1 January 1996 and 31 December 2007. Among 76 627 individuals there were 4414 deaths (3982 in men). When compared with the general population, the age-standardized mortality rate ratio for those imprisoned was 3.3 (95% CI: 3.2, 3.4) for men and 7.6 (6.9, 8.3) for women. Further adjustment for an area measure of deprivation accounted for part but not all of this excess risk [adjusted rate ratio 2.3 (2.2, 2.4) and 5.7 (5.1, 6.2) for men and women, respectively]. Relative risks were highest for drug and alcohol related causes, suicide and homicide and were markedly higher among women than men. Out of prison deaths were most frequent in the first 2 weeks after release from prison. Mortality rates were lower in those with longer total duration in prison and higher in those with multiple short episodes in prison. People who have been imprisoned in Scotland experience substantial excess mortality from a range of causes that is only partly explained by deprivation. The association of increased mortality with multiple periods in prison and the concentration of deaths in the early period after prison release both have implications for policy and practice.


Dysfunction of Human Estrogen Signaling as a Novel Molecular Signature of Polycystic Ovary Syndrome.
Estradiol (E2) is a major hormone-controlling folliculogenesis whose dysfunction may participate in polycystic ovary syndrome (PCOS) infertility. To determine whether both the concentration and action of E2 could be impaired in non-hyperandrogenic overweight PCOS women, we isolated granulosa cells (GCs) and follicular fluid (FF) from follicles of women undergoing ovarian stimulation (27 with PCOS, and 54 without PCOS). An analysis of the transcript abundance of 16 genes in GCs showed that androgen and progesterone receptor expressions were significantly increased in GCs of PCOS (by 2.7-fold and 1.5-fold, respectively), while those of the steroidogenic enzymes CYP11A1 and HSD3B2 were down-regulated (by 56% and 38%, respectively). Remarkably, treatment of GC cultures with E2 revealed its ineffectiveness in regulating the expression of several key endocrine genes (e.g., GREB1 or BCL2) in PCOS. Additionally, a comparison of the steroid concentrations (measured by GC/MS) in GCs with those in FF of matched follicles demonstrated that the significant decline in the E2 concentration (by 23%) in PCOS FF was not the result of the E2 biosynthesis reduction. Overall, our study provides novel hallmarks of PCOS by highlighting the ineffective E2 signaling in GCs as well as the dysregulation in the expression of genes involved in follicular growth, which may contribute to aberrant folliculogenesis in non-hyperandrogenic women with PCOS.


An epidemiological analysis of Acute Flaccid Paralysis (AFP) surveillance in Kenya, 2016 to 2018.
The poliovirus has been targeted for eradication since 1988. Kenya reported its last case of indigenous Wild Poliovirus (WPV) in 1984 but suffered from an outbreak of circulating Vaccine-derived Poliovirus type 2 (cVDPV2) in 2018. We aimed to describe Kenya's polio surveillance performance 2016-2018 using WHO recommended polio surveillance standards. Retrospective secondary data analysis was conducted using Kenyan AFP surveillance case-based database from 2016 to 2018. Analyses were carried out using Epi-Info statistical software (version 7) and mapping was done using Quantum Geographic Information System (GIS) (version 3.4.1). Kenya reported 1706 cases of AFP from 2016 to 2018. None of the cases were confirmed as poliomyelitis. However, 23 (1.35%) were classified as polio compatible. Children under 5 years accounted for 1085 (63.6%) cases, 937 (55.0%) cases were boys, and 1503 (88.1%) cases had received three or more doses of Oral Polio Vaccine (OPV). AFP detection rate substantially increased over the years; however, the prolonged health workers strike in 2017 negatively affected key surveillance activities. The mean Non-Polio (NP-AFP) rate during the study period was 2.87/ 100,000 children under 15 years, and two adequate specimens were collected for 1512 (88.6%) AFP cases. Cumulatively, 31 (66.0%) counties surpassed target for both WHO recommended AFP quality indicators. The performance of Kenya's AFP surveillance system surpassed the minimum WHO recommended targets for both non-polio AFP rate and stool adequacy during the period studied. In order to strengthen the country's polio free status, health worker's awareness on AFP surveillance and active case search should be strengthened in least performing counties to improve case detection. Similar analyses should be done at the sub-county level to uncover underperformance that might have been hidden by county level analysis.


Prevalence and risk factors for pulmonary arterial hypertension in a large group of β-thalassemia patients using right heart catheterization: a Webthal study.
Pulmonary arterial hypertension (PAH) remains a concern in patients with β-thalassemia major (TM) and intermedia (TI); however, studies evaluating its prevalence and risk factors using systematic confirmation on right heart catheterization are lacking. This was a multicenter cross-sectional study of 1309 Italian β-thalassemia patients (mean age 36.4±9.3 years; 46% men; 74.6% TM, 25.4% TI). Patients with a tricuspid-valve regurgitant jet velocity ≥3.2 m/s (3.6%) on transthoracic echocardiography further underwent right heart catheterization to confirm the diagnosis of PAH (mean pulmonary arterial pressure ≥25 mm Hg and pulmonary capillary wedge pressure ≤15mm Hg). The confirmed PAH prevalence on right heart catheterization was 2.1% (95% confidence interval [CI], 1.4-3.0) and was higher in TI (4.8%; 95% CI, 3.0-7.7) than TM (1.1%; 95% CI, 0.6-2.0). The positive predictive value for the tricuspid-valve regurgitant jet velocity ≥3.2 m/s threshold for the diagnosis of pulmonary hypertension was 93.9%. Considerable functional limitation and decrease in the 6-minute walk distance were noted in patients with confirmed PAH. On multivariate logistic regression analysis, independent risk factors for confirmed PAH were age (odds ratio, 1.102 per 1-year increase; 95% CI, 1.06-1.15) and splenectomy (odds ratio, 9.31; 95% CI, 2.57-33.7). The prevalence of PAH in β-thalassemia patients as confirmed on right heart catheterization was 2.1%, with an ≈5-fold higher prevalence in TI than TM. Advanced age and splenectomy are risk factors for PAH in this patient population. http://www.ClinicalTrials.gov. Unique identifier: NCT01496963.


Pharmacists' awareness of clinical decision support in pharmacy information systems: an exploratory evaluation.
Clinical decision support (CDS), such as drug-drug interaction (DDI) and drug-allergy checking, has been used in pharmacy information systems for several decades; however, there has been limited research on CDS use by practicing pharmacists. The purpose of this study was to document pharmacists' awareness of DDI and other medication-related CDS features available within pharmacy information systems. Researchers conducted on-site interviews with pharmacists throughout the state of Arizona from December 2008 to November 2009 regarding their pharmacy information systems features. Pharmacists were asked to provide information about DDI and other medication-related decision support features of the pharmacy software at their practice site. Descriptive statistics were used to summarize interview responses. Sixty-one pharmacists from a variety of practice settings completed the interview. All respondents indicated that their pharmacy system provided drug-allergy and DDI alerts. Approximately 60% of the pharmacists reported that their DDI decision support systems included recommendations for managing drug interactions. Two-thirds of respondents reported that their pharmacy's computer system permitted the addition of medications from other pharmacies and/or over-the-counter products to a patient's profile. Approximately 40% of the pharmacists reported that some drugs entered into the pharmacy computer system were not included in (or linked to) the electronic DDI checking. Most pharmacists indicated the presence of other medication-related decision support features, such as drug-disease (78%), drug-age precautions (67%), and inappropriate dosage alerts (79%). However, fewer pharmacists reported more advanced functionality, such as laboratory recommendations (34%) and pediatric dosing (39%). Overall, pharmacists' awareness regarding the many decision support functionalities of their systems was limited. Based on the study findings, it appears that there are a number of limitations associated with currently available pharmacy decision support software. Further research is needed to formally evaluate pharmacist knowledge of pharmacy decision support software functionality. More formal training about software capabilities coupled with the addition of more advanced decision support features has the potential to improve pharmacists' use of these systems to make better clinical decisions and avoid preventable errors.


The endocannabinoid system in Parkinson's disease.
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder of largely unknown etiology caused by a pathological cascade resulting in the degeneration of midbrain dopaminergic neurons of the substantia nigra pars compacta (SNpc) projecting to the nucleus striatum, the main input station of the basal ganglia neuronal circuit. The components of the endocannabinoid (ECB) system are highly expressed at different levels in the basal ganglia neural circuit where they bidirectionally interact with dopaminergic, glutamatergic and GABAergic signaling systems. In particular, at synapses linking cortical and striatal neurons, endocannabinoids (ECBs) are known to critically modulate synaptic transmission and to mediate the induction of a particular form of synaptic plasticity, the long-term depression. The evidence that ECBs play a central role in regulating basal ganglia physiology and motor function and the profound modifications occurring in ECB signaling after dopamine depletion in both experimental models of PD and patients suffering from the disease, provide support for the development of pharmacological compounds targeting the ECB system as symptomatic and neuroprotective therapeutic strategies for PD.


Survival of Toxoplasma gondii oocysts in Eastern oysters (Crassostrea virginica).
Toxoplasma gondii has recently been recognized to be widely prevalent in the marine environment. It has previously been determined that Eastern oysters (Crassostrea virginica) can remove sporulated T. gondii oocysts from seawater and that oocysts retain their infectivity for mice. This study examined the long-term survival of T. gondii oocysts in oysters and examined how efficient oysters were at removing oocysts from seawater. Oysters in 76-L aquaria (15 oysters per aquarium) were exposed to 1 x 10(6) oocysts for 24 hr and examined at intervals up to 85 days postexposure (PE). Ninety percent (9 of 10) of these oysters were positive on day 1 PE using mouse bioassay. Tissue cysts were observed in 1 of 2 mice fed tissue from oysters exposed 21 days previously. Toxoplasma gondii antibodies were found in 2 of 3 mice fed oysters that had been exposed 85 days previously. In another study, groups of 10 oysters in 76-L aquaria were exposed to 1 x 10(5), 5 x 10(4), or 1 x 10(4) sporulated T. gondii oocysts for 24 hr and then processed for bioassay in mice. All oysters exposed to 1 x 10(5) oocysts were infected, and 60% of oysters exposed to 5 x 10(4) oocysts were positive when fed to mice. The studies with exposure to 1 x 10(4) oocysts were repeated twice, and 10 and 25% of oysters were positive when fed to mice. These studies indicate that T. gondii can survive for several months in oysters and that oysters can readily remove T. gondii oocysts from seawater. Infected filter feeders may serve as a source of T. gondii for marine mammals and possibly humans.


Microsatellite instability of the colorectal carcinoma can be predicted in the conventional pathologic examination. A prospective multicentric study and the statistical analysis of 615 cases consolidate our previously proposed logistic regression model.
High microsatellite instability (MSI-H) allows the identification of a subset of colorectal carcinomas associated with good prognosis and a higher incidence of Lynch syndrome. The aim of this work was to assess the interobserver variability and optimize our MSI-H prediction model previously published based on phenotypic features.The validation series collected from five different hospitals included 265 primary colorectal carcinomas from the same number of patients. The eight clinicopathological parameters that integrate our original model were evaluated in the corresponding centers. Homogeneity assessment revealed significant differences between hospitals in the estimation of the growth pattern, presence of Crohn-like reaction, percentage of cribriform structures, and Ki-67 positivity. Despite this observation, our model was globally able to predict MSI-H with a negative predictive value of 97.0%. The optimization studies were carried out with 615 cases and resulted in a new prediction model RERtest8, which includes the presence of tumor infiltrating lymphocytes at the expense of the percentage of cribriform structures. This refined model achieves a negative predictive value of 97.9% that is maintained even when the immunohistochemical parameters are left out, RERtest6. The high negative predictive value achieved by our models allows the reduction of the cases to be tested for MSI to less than 10%. Furthermore, the easy evaluation of the parameters included in the model renders it a useful tool for the routine practice and can reinforce other published models and the current clinical protocols to detect the subset of colorectal cancer patients bearing hereditary nonpolyposis colorectal cancers risk and/or MSI-H phenotype.


Repair of large incisional hernias. To drain or not to drain. Randomized clinical trial.
To evaluate the occurrence of seroma and surgical wound infection after surgery. A total of 42 individuals with large incisional hernias were subjected toonlay mesh repair. Following the mesh placement, the participants were randomly allocated to two groups. In group 1, closed-suction drains were placed in the subcutaneous tissue, while progressive tension sutures were performed in group 2. The participants were subjected to clinical and ultrasound assessment to detect seroma and surgical wound infection at three time-points after surgery. The occurrence of seroma at the early, intermediate or late assessments was respectively 19.0%, 47.6%, 52.4% in group 1 and 28.6%, 57.1%, 42.9% in group 2 and was not significantly different between groups (p 0.469; 0.631; 0.619). Surgical wound infection occurred 19% in group 1 and 23.8% in group 2, without a significant difference between the groups (p>0.999). The frequency of seroma and infection did not exhibit significant differences between individuals subjected to onlay mesh repair of large incisional hernias with drains or progressive tension sutures without drainage.


PCR primers that can detect low levels of Mycobacterium leprae DNA.
There are several specific PCR-based methods to detect Mycobacterium leprae DNA, but the amplicons are quite large. For example, primers that target the 36-kDa antigen gene and are in common diagnostic use yield a 530-bp product. This may be a disadvantage when examining samples in which the DNA is likely to be damaged and fragmented. Therefore, two sets of M. leprae-specific nested primers were designed, based on existing primer pairs which have been shown to be specific for M. leprae. Primers that targeted the 18-kDa antigen gene gave an outer product of 136 bp and inner product of 110 bp. The primers based on the RLEP repetitive sequence yielded a 129-bp outer product and 99-bp nested product. With dilutions of a standard M. leprae killed whole-cell preparation as the source of DNA, both single-stage and nested PCR were performed after optimisation of the experimental conditions. Compared with the 36-kDa antigen gene primers, the 18-kDa antigen gene outer primers were 100-fold more sensitive and the RLEP outer primers were 1000-fold more sensitive. As an illustration of two possible applications of these new primers, positive results were obtained from three skin slit samples from treated lepromatous leprosy patients and three archaeological samples from human remains showing typical leprosy palaeopathology. It was concluded that these new primers are a useful means of detecting M. leprae DNA which is damaged or present at a very low level.


Novel 18F labeling strategy for polyester-based NPs for in vivo PET-CT imaging.
Drug-loaded nanocarriers and nanoparticulate systems used for drug release require a careful in vivo evaluation in terms of physicochemical and pharmacokinetic properties. Nuclear imaging techniques such as positron emission tomography (PET) are ideal and noninvasive tools to investigate the biodistribution and biological fate of the nanostructures, but the incorporation of a positron emitter is required. Here we describe a novel approach for the (18)F-radiolabeling of polyester-based nanoparticles. Our approach relies on the preparation of the radiolabeled active agent 4-[(18)F]fluorobenzyl-2-bromoacetamide ([(18)F]FBBA), which is subsequently coupled to block copolymers under mild conditions. The labeled block copolymers are ultimately incorporated as constituent elements of the NPs by using a modified nano coprecipitation method. This strategy has been applied in the current work to the preparation of peptide-functionalized NPs with potential applications in drug delivery. According to the measurements of particle size and zeta potential, the radiolabeling process did not result in a statistically significant alteration of the physicochemical properties of the NPs. Moreover, radiochemical stability studies showed no detachment of the radioactivity from NPs even at 12 h after preparation. The radiolabeled NPs enabled the in vivo quantification of the biodistribution data in rats using a combination of imaging techniques, namely, PET and computerized tomography (CT). Low accumulation of the nanoparticles in the liver and their elimination mainly via urine was found. The different biodistribution pattern obtained for the "free" radiolabeled polymer suggests chemical and radiochemical integrity of the NPs under investigation. The strategy reported here may be applied to any polymeric NPs containing polymers bearing a nucleophile, and hence our novel strategy may find application for the in vivo and noninvasive investigation of a wide range of NPs.


Isolation and characterization of microsatellite markers in Acca sellowiana (Berg) Burret.
Acca sellowiana has commercial potential because of the quality and the unique flavor of its fruit. Conservation of natural populations and management of breeding programmes would benefit from the availability of molecular markers that could be used to characterize levels and distribution of genetic variability. Thus, 13 microsatellite markers were developed from an enriched genomic library of A. sellowiana. They were characterized using 40 samples. The expected and observed heterozygosities ranged from 0.513 to 0.913 and from 0.200 to 0.889, respectively. These are the first microsatellite loci characterized from A. sellowiana that will contribute to improve researches on the genetic conservation, characterization and breeding.


Average is optimal: an inverted-U relationship between trial-to-trial brain activity and behavioral performance.
It is well known that even under identical task conditions, there is a tremendous amount of trial-to-trial variability in both brain activity and behavioral output. Thus far the vast majority of event-related potential (ERP) studies investigating the relationship between trial-to-trial fluctuations in brain activity and behavioral performance have only tested a monotonic relationship between them. However, it was recently found that across-trial variability can correlate with behavioral performance independent of trial-averaged activity. This finding predicts a U- or inverted-U- shaped relationship between trial-to-trial brain activity and behavioral output, depending on whether larger brain variability is associated with better or worse behavior, respectively. Using a visual stimulus detection task, we provide evidence from human electrocorticography (ECoG) for an inverted-U brain-behavior relationship: When the raw fluctuation in broadband ECoG activity is closer to the across-trial mean, hit rate is higher and reaction times faster. Importantly, we show that this relationship is present not only in the post-stimulus task-evoked brain activity, but also in the pre-stimulus spontaneous brain activity, suggesting anticipatory brain dynamics. Our findings are consistent with the presence of stochastic noise in the brain. They further support attractor network theories, which postulate that the brain settles into a more confined state space under task performance, and proximity to the targeted trajectory is associated with better performance.


A systematic account of the genus Plagiostoma (Gnomoniaceae, Diaporthales) based on morphology, host-associations, and a four-gene phylogeny.
Members of the genus Plagiostoma inhabit leaves, stems, twigs, and branches of woody and herbaceous plants predominantly in the temperate Northern Hemisphere. An account of all known species of Plagiostoma including Cryptodiaporthe is presented based on analyses of morphological, cultural, and DNA sequence data. Multigene phylogenetic analyses of DNA sequences from four genes (β-tubulin, ITS, rpb2, and tef1-α) revealed eight previously undescribed phylogenetic species and an association between a clade composed of 11 species of Plagiostoma and the host family Salicaceae. In this paper these eight new species of Plagiostoma are described, four species are redescribed, and four new combinations are proposed. A key to the 25 accepted species of Plagiostoma based on host, shape, and size of perithecia, perithecial arrangement in the host, and microscopic characteristics of the asci and ascospores is provided. Disposition of additional names in Cryptodiaporthe and Plagiostoma is also discussed.


Identification of upregulated genes in scrapie-infected brain tissue.
The pathogenesis of scrapie, and of neurodegenerative diseases in general, is still insufficiently understood and is therefore being intensely researched. There is abundant evidence that the activation of glial cells precedes neurodegeneration and may thus play an important role in disease development and progression. The identification of genes with altered expression patterns in the diseased brain may provide insight on the molecular level into the process which ultimately leads to neuronal loss. Differentially expressed genes in scrapie-infected brain tissue were enriched by the suppression subtractive hybridization technique, molecularly cloned, and further characterized. Northern blotting and nucleotide sequencing confirmed the identities of 19 upregulated genes, 11 of which were unknown to be affected by scrapie. A considerable number of these 19 genes, namely those encoding interferon-inducible protein 10 (IP-10), 2',5'-oligo(A) synthetase, Mx protein, IIGP protein, major histocompatibility complex classes I and II, complement, and beta(2)-microglobulin, were inducible by interferons (IFNs), suggesting that an IFN response is a possible mechanism of gene activation in scrapie. Among the newly found genes, that coding for 2',5'-oligo(A) synthetase is of special interest because it could contribute to the apoptotic loss of neuronal cells via RNase L activation. In addition, upregulation of the chemokine IP-10 and B-lymphocyte chemoattractant mRNAs was seen at relatively early stages of the disease and was sustained throughout disease development.


Automated gesture tracking in head-fixed mice.
The preparation consisting of a head-fixed mouse on a spherical or cylindrical treadmill offers unique advantages in a variety of experimental contexts. Head fixation provides the mechanical stability necessary for optical and electrophysiological recordings and stimulation. Additionally, it can be combined with virtual environments such as T-mazes, enabling these types of recording during diverse behaviors. In this paper we present a low-cost, easy-to-build acquisition system, along with scalable computational methods to quantitatively measure behavior (locomotion and paws, whiskers, and tail motion patterns) in head-fixed mice locomoting on cylindrical or spherical treadmills. Several custom supervised and unsupervised methods have been developed for measuring behavior in mice. However, to date there is no low-cost, turn-key, general-purpose, and scalable system for acquiring and quantifying behavior in mice. We benchmark our algorithms against ground truth data generated either by manual labeling or by simpler methods of feature extraction. We demonstrate that our algorithms achieve good performance, both in supervised and unsupervised settings. We present a low-cost suite of tools for behavioral quantification, which serve as valuable complements to recording and stimulation technologies being developed for the head-fixed mouse preparation.


Postreplantation management of avulsed teeth: an endodontic literature review.
Today's dental treatment goals are directed at reducing the incidence of root resorption resulting from periodontal ligament devitalization or pulp necrosis. Although the American Association of Endodontists recommends the use of long-term therapy, short-term therapy may be utilized with confidence in well-defined clinical applications. Early final obturation with gutta-percha will increase the long-term prognosis in those cases where patient motivation is questionable or long-term follow-up prior to obturation is not possible. However, where inflammatory resorption is already present, long-term calcium hydroxide therapy is indicated. Long-term post treatment follow-up is imperative in both calcium hydroxide therapies.


[Studies of the discus articularis ulnae by use of arthrography of the wrist joint].
Lesions of the "discus articularis ulnae" (triangular fibrocartilage) are presented. Possible differences between the left and the right hand, as well as possible age and sex-linked differences were statistically analysed. In 22 wrist the disc was removed. The anatomical and pathological findings correlated with the arthrogram in all cases. Due probably to the advanced age of our study material disc lesions were found to be more frequent than in previous studies. The lesion was less frequent in men than in women. No difference could be shown between the left and the right hand. The arthrographic variations of the joint spaces adjoining the wrist were found to be symmetrically distributed. In no case could a communication between the wrist and the distal radioulnar joint be shown.


[Homocarnosine metabolism in brain tissue].
In glial tumors of human brain the content of homocarnosine has been found to be lower than in brain tissue. In experimental animals cranial injury induces an increase of homocarnosine in brain tissue. Stimulation of the nervous system of traumatized animals by phenamin brings the metabolism of homocarnosine back to normal. The results of these studies make us suppose that homocarnosine is a substance involved in brain activity.


Fos-protein expression in noradrenergic locus coeruleus neurons after unilateral labyrinthectomy in the rat.
c-Fos mRNA and the related Fos-protein are rapidly induced by physiological stimuli and can be used as molecular markers of neural activation and plasticity. In a recent study (14), we found that rats submitted to unilateral labyrinthectomy (UL) displayed an asymmetric increase in the expression of both c-fos and Fos-protein not only in several vestibular, precerebellar and cerebellar structures and the caudate-putamen, but also in the locus coeruleus (LC)-complex, whose neurons integrate labyrinthine signals and are apparently involved in the plastic changes which are at the basis of vestibular compensation. In the present study we investigated the putative noradrenergic nature of the Fos-positive LC neurons observed after UL by combining Fos-protein immunocytochemistry with the immunocytochemical detection of tyrosine hydroxylase (TH), a synthetizing enzyme of noradrenaline. The experiments were performed in rats sacrificed 3, 6 and 24 h after surgical lesion of one labyrinth. The results obtained were in agreement with the previous findings, showing that already 3 h after UL an asymmetric increase of the c-fos and/or Fos-protein expression occurred in the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen. Most interestingly, the Fos-protein expression markedly increased in the LC-complex of both sides, although mainly ipsilaterally to the intact side. It appeared also that several Fos-positive LC-complex neurons were probably noradrenergic in nature, as they could be double-labeled with the Fos/TH technique. These findings were attenuated 6 h after UL and disappeared after 24 h, when partial compensation of the vestibular syndrome had occurred. Thus, UL results in asymmetric functional activation in the LC region of well identified noradrenergic neurons. This finding is attributed to the fact that asymmetric stimulation of labyrinth receptors gives rise to asymmetric changes in firing rate of LC neurons (45). Since these neurons send noradrenergic afferents to several target structures such as the vestibular nuclei, the inferior olive, the cerebellar cortex and the caudate-putamen, we postulated that the asymmetric labyrinthine activation of the noradrenergic LC system, occurring after UL, could increase the Fos-protein expression in the above mentioned brain structures. This possibility could then represent a key factor in determining the plastic changes, which are at the basis of vestibular compensation.


Adherence of the dysphonic teachers in speech therapy.
To study the possible factors associated with adherence to the speech-language pathology treatment of dysphonia in female teachers of municipal schools of Belo Horizonte. This was a retrospective study that analyzed the medical records of 251 teachers treated at the Voice Ambulatory Speech Language Pathology Service, Hospital das Clínicas da Universidade Federal de Minas Gerais (AV-UFMG) from August 2007 to December 2009. The collected data included age, number of scheduled sessions, number of absences, number of children, type of dysphonia, degree of dysphonia, monthly family income, and education. We calculated the distance, in kilometers, of the residence to the place of treatment and the workplace to place of treatment. We also analyzed the social vulnerability index of the workplace. The results of this research indicated that of the 135 records that were included in the study, 89 (65.93%) corresponded to the discharged group and 46 (34.07%) corresponded to the abandonment group. In comparison with all the variables studied, only the number of faults and the type of dysphonia were associated with poor adherence to voice therapy. Results showed that the number of absences in sessions, treatment-related factor, organofuncional dysphonia type, and clinical-related factor were all associated with the abandonment of voice therapy.


Awareness and knowledge of osteoporosis in Vietnamese women.
Vietnamese women are at particular risk of osteoporosis and its complications. This study examined osteoporosis knowledge and awareness among Vietnamese women who have accessed health care. A sample of 217 women, 13 to 76 years of age, who were attending 1 of 2 health care facilities in Da Nang, Vietnam, between November and December 2009 completed a questionnaire assessing their awareness of osteoporosis and measuring their knowledge using a 30-item instrument reflecting 9 knowledge domains (eg, risk factors, diagnosis, prognosis). A majority (81.6%) of the women had heard of osteoporosis. Awareness was associated with education, working in health care, and having a family member with osteoporosis. On average, Vietnamese women answered 49% of the knowledge questions correctly; scores ranged from 0 to 26 questions correct out of 30 (mean = 14.71 ± 5.2, median = 15). Mean knowledge scores were higher among those reporting a family member with osteoporosis, nurses (vs other vocations), and women with a high school education or greater (relative to those who had not completed high school). More than 90% of the women expressed interest in a prevention and treatment program. Vietnamese women may have heard of osteoporosis, yet they would benefit from education targeting prevention and treatment of the disease.


Scots pine needle surfaces on radial transects across the north boreal area of Finnish Lapland and the Kola Peninsula of Russia.
To gain an understanding of the characteristics of the needle surfaces of naturally regenerated Scots pine (Pinus sylvestris L.) and their geographical distribution, eight physicochemical variables were investigated within the north boreal forest area. The visibly undamaged needles were collected in autumn 1990 from 114 plots (3-5 pines per plot) along radial transects from the Monchegorsk and Nikel smelters, emitting SO2 and heavy metals, on the Kola Peninsula, Russia, to Finnish Lapland. The needles were examined by scanning electron microscopy (SEM) and measured for surface wettability using the droplet contact angle (DCA) method. Significant geographical south-north and west-east patterns could be observed in needle surface characteristics, correlating with emissions from the smelters and to climate. Despite the slightly higher initial DCAs (61.4-87.6 degrees) towards the north, the pine needle surfaces of the northernmost transects exhibited higher annual needle wettability change (ANWC) and wax erosion rate (AWER), expressed as the reduction in DCAs and epistomatal wax tube distribution (WTD) during one year, respectively, but a lower occurrence of particles and fungal hyphae than those of more southern transects. The higher ANWC was related to higher atmospheric SO2 concentration, and to the lower long-term temperature sum, but not clearly to annual precipitation. In the Monchegorsk smelter area, the current needles exhibited, on average, a 15% higher WTD and seven degree larger DCA, resulting in more hydrophobic needle surfaces than in Finnish Lapland, but during their first year, both the AWER and ANWC, were greatly increased. In Finnish Lapland, 30%, of all the epistomatal wax tubes disappeared from the needle surface during the first year, the value being 70% for the pines located 8 km from the smelter. The mineral composition of the particles deposited on the needle surfaces mirrored that of the minerals being produced by the smelters (e.g. FexSx, CuFeS2, NixSx, FexOx). Stomatal densities were in the range of 71.1-141.7 stomata mm(-2). The lower densities of stomata on needles close to the smelters correlated with reduced number of needle age classes of the pines, higher dry weights, higher pollutant accumulation and lower Mn and Zn concentrations in the needles. The AWER and ANWC were able to indicate the most seriously deteriorated needle surfaces on a regional scale, e.g. including the surroundings of both smelters, although the plot-specific relationships between 'needle surface variables' and 'pollution variables' were generally weak. The present study showed that the exposure of pine needles to the combined effects of ambient pollutants and harsh climate led to a deterioration in the physicochemical characteristics of the epicuticular wax, which may have serious ecophysiological consequences in the long term.


Versatile Functionalization of P25 Conjugated ND Nanocomposites for UV-Mediated Free Radical Scavenging and Facilitates Anti-Inflammation Potential in Human Cells.
In this work, we demonstrated that building different linking groups between nanodiamond (ND) and TiO2 (P25) could provide more effective protection under oxidative stress and ultraviolet (UV) light irradiation compared with the use of TiO2 alone. The establishment of ester (-C-O-O-R), amide (-CONH-), and epoxide-amine adduct (-NHCCO-) groups between ND-TiO2 composites was found to be critical in the generation of reactive oxygen species (ROS) by controlling their charge transfer behaviors. We hypothesized that linking groups between the composites dictate the performance of ROS generation from nano-TiO2 under UV-light irradiation due to the differences in linking groups. The results showed that hydroxyl radicals were attenuated by the incorporation of ND. An MTT cell proliferation assay was performed in human cells under the treatment of ND-TiO2 composites to investigate the impacts of composites on cell viability. The results from the luciferase reporter assay suggested they have anti-inflammatory activity and can reduce cellular DNA damage under ROS stimulation. A zebrafish model was also applied with the ND-TiO2 composite treatment to demonstrate the safety aspects of the composites in vivo and their biomedical application potential. Studies exploring ROS generation behaviors in different linking groups suggested that interactive functionalization between nanoparticles might be an ideal antioxidant and anti-inflammatory strategy.


American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer.
To develop a clinical practice guideline for treatment of laryngeal cancer with the intent of preserving the larynx (either the organ itself or its function). This guideline is intended for use by oncologists in the care of patients outside of clinical trials. A multidisciplinary Expert Panel determined the clinical management questions to be addressed and reviewed the literature available through November 2005, with emphasis given to randomized controlled trials of site-specific disease. Survival, rate of larynx preservation, and toxicities were the principal outcomes assessed. The guideline underwent internal review and approval by the Panel, as well as external review by additional experts, members of the American Society of Clinical Oncology (ASCO) Health Services Committee, and the ASCO Board of Directors. Evidence supports the use of larynx-preservation approaches for appropriately selected patients without a compromise in survival; however, no larynx-preservation approach offers a survival advantage compared with total laryngectomy and adjuvant therapy with rehabilitation as indicated. All patients with T1 or T2 laryngeal cancer, with rare exception, should be treated initially with intent to preserve the larynx. For most patients with T3 or T4 disease without tumor invasion through cartilage into soft tissues, a larynx-preservation approach is an appropriate, standard treatment option, and concurrent chemoradiotherapy therapy is the most widely applicable approach. To ensure an optimum outcome, special expertise and a multidisciplinary team are necessary, and the team should fully discuss with the patient the advantages and disadvantages of larynx-preservation options compared with treatments that include total laryngectomy.


Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.
Mantle cell lymphoma (MCL) is typically a very aggressive disease with poor outcomes, but some cases display an indolent behavior that might not necessitate treatment at diagnosis. To define molecular criteria that might permit recognition of such cases, we compared the clinicopathologic features, gene expression, and genomic profile of patients who had indolent or conventional disease (iMCL or cMCL). Patients with iMCL displayed nonnodal leukemic disease with predominantly hypermutated IGVH and noncomplex karyotypes. iMCL and cMCL shared a common gene expression profile that differed from other leukemic lymphoid neoplasms. However, we identified a signature of 13 genes that was highly expressed in cMCL but underexpressed in iMCL. SOX11 was notable in this signature and we confirmed a restriction of SOX11 protein expression to cMCL. To validate the potential use of SOX11 as a biomarker for cMCL, we evaluated SOX11 protein expression in an independent series of 112 cases of MCL. Fifteen patients with SOX11-negative tumors exhibited more frequent nonnodal presentation and better survival compared with 97 patients with SOX11-positive MCL (5-year overall survival of 78% versus 36%, respectively; P = 0.001). In conclusion, we defined nonnodal presentation, predominantly hypermutated IGVH, lack of genomic complexity, and absence of SOX11 expression as qualities of a specific subtype of iMCL with excellent outcomes that might be managed more conservatively than cMCL.


Apparent reinfection of enzootic-pneumonia-free pig herds: search for possible causes.
In a control scheme for enzootic-pneumonia-free herds, run by the Pig Health Control Association, a detailed study was made of 55 herds that developed enzootic pneumonia without a simple explanation. These herds were compared with 57 herds that were still free from enzootic pneumonia in mid-1984. A high standard of precautions against the risk of infection being transferred by people and fomites seemed to confer no obvious benefit. This observation was in keeping with in vitro studies which showed that, although Mycoplasma hyopneumoniae could survive for a long time in favourable liquid medium, it could not be recovered from material such as cloth, once the culture had become dry. Under field conditions, the organism would probably cease to be infective within 48 hours. The organism survived particularly well in rain water at lower temperatures, however, and transmission via moist cold air seemed a possibility. There was a tendency for breakdowns to start in the autumn and winter, particularly in highly secure units, and several farmers associated colder misty conditions with the arrival of infection. One herd was probably infected by an imported boar and the very close proximity of foreign pigs, such as in slaughterhouse transport, seemed the most likely explanation in 15 other herds. One herd was replaced without this danger being attended to and it soon broke down again, whereas the three herds in this category that have survived after replacement all had this risk eliminated. Data was available on 37 of the 39 remaining herds to compare them with the 57 surviving herds, using a risk index based on the proximity of other pig units.(ABSTRACT TRUNCATED AT 250 WORDS)