bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of stature from percutaneous length of tibia in the population of Birgunj, Nepal
Authors: Sah Rajendra Prasad , Shrestha Iju
Published: October 2014

Background: Stature estimation is one of the important parameters in establishment of the identity of a person. As said “Identification is an individual’s birth right”, stature of an individual is an inherent character. Mass disasters like aircrash, terrorist attacks etc. are quite frequent these days because of which dismembered body parts are being frequently brought to the medico-legal experts for generating data for identification.Objective: The objective of this study is to estimate the stature from percutaneous tibia length (PCTL).Methods: This prospective study consisted of 150 males and 150 females between the age group of 20 to 30 years, born and brought up in Nepal. The duration of study is one year from October 2012 to October 2013. The parameters measured were stature and percutaneous tibia length. To find out the correlation of percutaneous tibial length with that of the height and to evolve a regression equation formula necessary statistical evaluation has been done on the data obtained from 300 adult participants comprising of 150 males and 150 females. By using the regression equation formula so derived the height of an individual can be calculated by the help of percutaneous tibial length. The data were analysed using Statistical Package for Social Sciences (SPSS) version 11. P value less than 0.05 was considered as a significant.Results: It was found that a significant positive correlation existed between the stature and percutaneous tibial length with a correlation coefficient (r) of 0.562 in males and 0.71 in females and p value <0.001. Stature was estimated from PCTL using simple regression analysis Stature (cm) = 88.898+2.027 * PCTL (cm) for males and Stature (cm) = 75.954+2.253 * PCTL (cm) for females.Conclusion: A highly significant correlation of stature was observed with percutaneous length in both sexes. The result of this study would be useful for anthropologists and forensic medicine experts. Stature can be estimated from PCTL using simple regression analysis.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11227Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page : 58-62
Double J stenting compared with ureteral catheterization in percutaneous Nephrolithotomy
Authors: Joshi Robin , Sharma Aakriti Sharma , Dongol Uday Man Singh , Singh Deepak Raj
Published: October 2014

Background:Nephrolithiasis represents a large portion in the field of Urological pathology. Minimal invasive and non-invasive therapies have become more accessible and efficient in the treatment of nephrolithiasis. Percutaneous nephrolithotomy (PCNL) is an effective minimal invasive modality of treating kidney stones.Objectives: To evaluate the outcome of standard percutaneous nephrolithotomy (PCNL) using two different stenting techniques i.e. externalized ureteral catheter placement compared with Double-J stent placement.Methods: This is a prospective study conducted from January 2012 to June 2013 at Kathmandu Medical College Teaching Hospital among patients undergoing percutaneous nephrolithotomy (PCNL). Fifty patients who underwent PCNL were divided into two equal groups: Group 1 (PCNL with Double-J stent placement) and Group 2 (PCNL with externalized ureteral catheter placement). Factors evaluated included stent-related symptoms, postoperative morbidity, and the cost. Morbidity was classified according to the Modified Clavien classification. SPSS 20 was used for statistical evaluation. P value less than 0.05 was considered significant.Results: Stent related morbidity were fever, dysuria, hematuria, burning micturition. Total of 16 stent related complications were seen in group 1 with four of the patients needing early surgical intervention to remove the Double J stent and injectable antibiotics for urinary tract complication due to in dwelling stent. In Group 2, seven patients experienced postoperative complications, out of which six were managed conservatively and one patient had grade III A dysuria and hematuria, who underwent immediate stent removal and received injectable antibiotics. There was no reported sepsis and mortality in both groups. Stent was removed in 3-4 weeks’ time in group 1 and 3-4 days in group 2. In Group 1, patients had to come one day prior for stent removal. Cost for DJ stent was significantly higher in group I than group II.Conclusion: Standard PCNL with externalized ureteral catheter is as feasible as Double-J stenting. Less cost can be a huge relief to the patients in the third world developing country.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11228Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page : 63-67
Anthropometric study of cephalic index among medical students in Nepal
Authors: Timsina Ram Prasad , Gogoi Paramananda
Published: October 2014

Background: Cephalic index is the ratio of the maximum breadth of head to its maximum length that is expressed as a percentage. Anthropometric measurements, especially craniofacial measurements, are important for determining various head and face shapes. These anthropometric studies are conducted on the age, sex and racial/ethnic groups in certain geographical zones.Objectives: The objectives of this study were to find out racial classification and their differences in Nepalese medical students anthropologically and to compare these with the data from other ethnic caste for use in anthropometric and forensic studies.Method: This is a descriptive and cross sectional study on 940 undergraduate medical students of age 17 to 27 years, with 455 males and 485 females from the three different medical colleges of Nepal. The head length (cm) and breadth (cm) were measured by spreading calliper. The height (cm) and weight of the participants were recorded. All the collected data were summarized using statistical package for social sciences (SPSS) 16.0 versions and their significance was tested by student t-test.Results: The mean cephalic index of 455 males and 485 females were 80.99% and 83.34% respectively. The cephalic index varied from the range of 71.20 to 97.40 in female and 72.08 to 96.77 in male. The dominant type of head shape in our study was mesocephalic (50.76%) followed by brachycephalic (32.74%).Conclusion: This study showed the head type of Nepalese was brachycephalic predominant but with the tendency to mesocephalic and hyperbrachycephalic.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11229Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page: 68-71
Dentists' perspective on preference for direct restorative materials for different tooth cavities: A study from two colleges in Kathmandu, Nepal
Authors: Poudel Keshav Raj , Gautam Suman , Pokhrel Prenit , Raghubanshi Bijendra Raj , Shrestha Amshuman , Raut Binod
Published: October 2014

Background: Restoration of carious teeth is required to preserve anatomy, function and aesthetics of a tooth. Proper restoration of carious teeth is paramount for the prevention of progression of a dental caries so as to obviate the need for root canal treatment. Location, extent, type, duration and cost play the major roles for the selection of a dental filling material.Objective: This study was set to know the preference of dentists for the selection of filling materials for different tooth cavities.Methods: This was cross-sectional observational study carried out at Kantipur Dental College and KIST Medical College for a period of six months. Pre-structured questionnaires were distributed to the dentists who were in dental practice and collected questionnaires were analyzed for the results. Data were compiled, entered and analyzed using Microsoft Excel 2007 and Epi Info 2000. Yates corrected Chi square test was used wherever applicable and level of significance was set at <0.05.Results: Out of 65 questionnaires distributed to the dental practitioners, 57 (87.7%) questionnaires were returned. Composite was the material of choice as the restorative material for all kinds of tooth cavities except for class V for which glass ionomer cement was the main choice (52.6%). After composite, dental amalgam was second most preferred material for posterior tooth restorations. Order of preference for filling materials for posterior restorations were: composite (52.6%), dental amalgam (47.4%), miracle mix (68.3%; P<0.05) and glass ionomer cement (42.1%). Majority of practitioners (78.9%,P<0.05) opined that strength and durability of restorative material is the main guiding factor for the selection of the filling material for posterior tooth restorations. Additionally, dental amalgam had higher (68%, P< 0.05) patient satisfaction with respect to cost and longevity or durability and was associated with less tiring and time consuming procedure (84%; P<0.05) on dentists’ view.Conclusion: Majority of dentists opined that composite is the more preferred filling material for both anterior and posterior tooth restorations. For posterior tooth cavities (mainly for class I, II and VI) after composite, the order preference for filling materials was amalgam, miracle mix and glass ionomer cement.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11230Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page: 72-77
Study of canthal index in Nepalese undergraduate medical students of BPKIHS, Nepal: gender and ethnic differences
Authors: Shah Sandip , Koirala Sarun
Published: October 2014

Background: Craniofacial anthropometry is a technique used in both physical and clinical anthropology comprising precise and systematic measurements of the human skull. It also includes measurement of the medial and lateral canthal distances. People of different genetic background subjected to significantly different environmental influences have different craniofacial morphology.Objectives: To find out effect of gender and ethnicity on Canthal anthropometry.Methods: This descriptive cross-sectional study was carried out to determine and compare canthal anthropometry among 299 undergraduate students (Male=161, Female=138) of different ethnic groups (Indo-Nepalese, indigenous and Tibeto-Nepalese) of age group 19-21 years at BPKIHS. Medial and lateral canthal distances were measured by using straight vernier caliper and canthal index (medial canthal distances / lateral canthal distance × 100) for all three ethnic groups in both sexes were compared.Results: The study has shown that the female students had higher canthal index than male students (27.65±12.35 vs 23.96±5.76). When compared on the basis of ethnicity, Indo-Nepalese had highest value of canthal index followed by Indigenous and Tibeto-Nepalese.Conclusion: In conclusion, genetics and environmental factors are responsible for the variation in canthal indices and other craniofacial indices between and within populations. Therefore, its standard values are largely applicable for clinical assessment of patients with syndrome affecting canthal anatomy.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11231Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page: 78-81
Anomalies of Mullerian ducts
Authors: Padhye Saraswati M
Published: October 2014

Some form of mullerian anomalies occur in one out of 4000 to 5000 females. A girl presenting with primary amenorrhoea, pelvic pain and sub fertility is likely to have some or other form of mullerian anomalies. Here, we present seven cases of mullerian anomalies who were treated at Kathmandu Medical college Teaching hospital in seven years. Absence of vagina usually is not obvious in a female baby at the time of birth. It is only when the secondary sex characters develop; time of menarche is awaited but one does not menstruate that the parents start wondering why her menstruation did not start.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11232Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page: 82-87
Piebaldism: A rare presentation in Nepalese context
Authors: Bhattarai Sabina , Maskey Sandesh , Joshi Aishana
Published: October 2014

Piebaldism is a rare autosomal dominant disorder characterised by a congenital white forelock and multiple symmetrical hypopigmented or depigmented macules. We present a case of an 18 year old male with a typical clinical presentation, followed by a concise review of the literature discussing the genetics, clinical features, diagnosis, and management of the condition. This is the first case of Piebaldism to be reported from Nepal with a good cosmetic surgery outcome.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11233Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page: 88-91
Congenital parameatal cyst: A case report
Authors: Mahato Shyam Kumar , Chaudhary Nagendra , Lama Susana , Bhatia Baldev
Published: October 2014

Parameatal urethral cyst is a benign congenital anomaly which occurs in newborn, children or even in adults. Most area symptomatic and rarely present with urinary complaints. We report a case of an asymptomatic male newborn with congenital parameatal cyst which was recognized just after birth. Complete excision of the cyst with total removal of the epithelium is required for treatment and for prevention of recurrence.DOI: http://dx.doi.org/10.3126/jkmc.v3i2.11235Journal of Kathmandu Medical CollegeVol. 3, No. 2, Issue 8, Apr.-Jun., 2014Page: 92-93
An Unexpected Catalytic Synthesis of Novel and Known Bis(Pyrazolyl) Methanes by the use of α-aryl-N-phenyl Nitrones in Aqueous Media
Authors: Eskandari Khalil , Karami Bahador , Khodabakhshi Saeed
Published: October 2014

Reaction of-aryl- N-phenyl nitrones with 3-methyl-1-phenyl-2-pyrazoline-5-one in the presence of a catalytic amount of silica tungstic acid in EtOH/H2O afforded, unexpectedly, high yields of bis(3-hydroxy-1-phenylpyrazolyl)-arylmethanes instead of the two possible 1,3-addition products. This is the first report of the synthesis of bis(3-hydroxy-1-phenylpyrazolyl)-arylmethanes via the reaction of nitrones and a pyrazolin-5-one. A possible mechanism for the process is suggested.
A Facile Synthesis of Imidazolidine-2,4,5-Trione
Authors: Yang De-Li , Li Jia-Rong , Lu Hong-Yan , Zhang Pan , Shi Da-Xin
Published: October 2014

When glycoluril was oxidised with potassium persulfate, the main product was imidazolidine-2,4,5-trione. The structure of product was confirmed by IR, ESI, 1H NMR and X-ray crystal structure determination.
Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration
Authors: Chen Yan , Williams Vonetta , Filippova Maria , Filippov Valery , Duerksen-Hughes Penelope
Published: October 2014

Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.
A GMM-Based Test for Normal Disturbances of the Heckman Sample Selection Model
Authors: Pfaffermayr Michael
Published: October 2014

The Heckman sample selection model relies on the assumption of normal and homoskedastic disturbances. However, before considering more general, alternative semiparametric models that do not need the normality assumption, it seems useful to test this assumption. Following Meijer and Wansbeek (2007), the present contribution derives a GMM-based pseudo-score LM test on whether the third and fourth moments of the disturbances of the outcome equation of the Heckman model conform to those implied by the truncated normal distribution. The test is easy to calculate and in Monte Carlo simulations it shows good performance for sample sizes of 1000 or larger.
Seasonal Pattern of Decomposition and N, P, and C Dynamics in Leaf litter in a Mongolian Oak Forest and a Korean Pine Plantation
Authors: Sohng Jaeeun , Han Ah , Jeong Mi-Ae , Park Yunmi , Park Byung , Park Pil
Published: October 2014

Distinct seasons and diverse tree species characterize temperate deciduous forests in NE Asia, but large areas of deciduous forests have been converted to conifer plantations. This study was conducted to understand the effects of seasons and tree species on leaf litter decomposition in a temperate forest. Using the litterbag method, the decomposition rate and nitrogen, phosphorous, and carbon dynamics of Mongolian oak (Quercus mongolica), Korean pine (Pinus koraiensis), and their mixed leaf litter were compared for 24 months in a Mongolian oak stand, an adjacent Korean pine plantation, and a Mongolian oak—Korean pine mixed stand. The decomposition rates of all the leaf litter types followed a pattern of distinct seasonal changes: most leaf litter decomposition occurred during the summer. Tree species was less influential on the leaf litter decomposition. The decomposition rates among different leaf litter types within the same stand were not significantly different, indicating no mixed litter effect. The immobilization of leaf litter N and P lasted for 14 months. Mongolian oak leaf litter and Korean pine leaf litter showed different N and P contents and dynamics during the decomposition, and soil P2O5 was highest in the Korean pine plantation, suggesting effects of plantation on soil nutrient budget.
Heparin Assisted Photochemical Synthesis of Gold Nanoparticles and Their Performance as SERS Substrates
Authors: Del Pilar Rodríguez-Torres Maria , Díaz-Torres Luis , Romero-Servin Sergio
Published: October 2014

Reactive and pharmaceutical-grade heparins were used as biologically compatible reducing and stabilizing agents to photochemically synthesize colloidal gold nanoparticles. Aggregates and anisotropic shapes were obtained photochemically under UV black-light lamp irradiation (λ = 366 nm). Heparin-functionalized gold nanoparticles were characterized by Scanning Electron Microscopy and UV-Vis spectroscopy. The negatively charged colloids were used for the Surface Enhanced Raman Spectroscopy (SERS) analysis of differently charged analytes (dyes). Measurements of pH were taken to inspect how the acidity of the medium affects the colloid-analyte interaction. SERS spectra were taken by mixing the dyes and the colloidal solutions without further functionalization or addition of any aggregating agent.
Identification of FactorsInfluencing the Puumala Virus Seroprevalence within Its Reservoir in aMontane Forest Environment
Authors: Thoma Bryan , Müller Jörg , Bässler Claus , Georgi Enrico , Osterberg Anja , Schex Susanne , Bottomley Christian , Essbauer Sandra
Published: October 2014

Puumala virus (PUUV) is a major cause of mild to moderate haemorrhagic fever with renal syndrome and is transmitted by the bank vole (Myodes glareolus). There has been a high cumulative incidence of recorded human cases in South-eastern Germany since 2004 when the region was first recognized as being endemic for PUUV. As the area is well known for outdoor recreation and the Bavarian Forest National Park (BFNP) is located in the region, the increasing numbers of recorded cases are of concern. To understand the population and environmental effects on the seroprevalence of PUUV in bank voles we trapped small mammals at 23 sites along an elevation gradient from 317 to 1420m above sea level. Generalized linear mixed effects models(GLMEM) were used to explore associations between the seroprevalence of PUUV in bank voles and climate and biotic factors. We found that the seroprevalence of PUUV was low (6%–7%) in 2008 and 2009, and reached 29% in 2010. PUUV seroprevalence was positively associated with the local species diversity and deadwood layer, and negatively associated with mean annual temperature, mean annual solar radiation, and herb layer. Based on these findings, an illustrative risk map for PUUV seroprevalence prediction in bank voles was created for an area of the national park. The map will help when planning infrastructure in the national park (e.g., huts, shelters, and trails).
Room temperature, ppb-level NO2 gas sensing of multiple-networked ZnSe nanowire sensors under UV illumination
Authors: Park Sunghoon , Kim Soohyun , Lee Wan In , Kim Kyoung-Kook , Lee Chongmu
Published: October 2014

Reports of the gas sensing properties of ZnSe are few, presumably because of the decomposition and oxidation of ZnSe at high temperatures. In this study, ZnSe nanowires were synthesized by the thermal evaporation of ZnSe powders and the sensing performance of multiple-networked ZnSe nanowire sensors toward NO2 gas was examined. The results showed that ZnSe might be a promising gas sensor material if it is used at room temperature. The response of the ZnSe nanowires to 50 ppb–5 ppm NO2 at room temperature under dark and UV illumination conditions were 101–102% and 113–234%, respectively. The responses of the ZnSe nanowires to 5 ppm NO2 increased from 102 to 234% with increasing UV illumination intensity from 0 to 1.2 mW/cm2. The response of the ZnSe nanowires was stronger than or comparable to that of typical metal oxide semiconductors reported in the literature, which require higher NO2 concentrations and operate at higher temperatures. The origin of the enhanced response of the ZnSe nanowires towards NO2 under UV illumination is also discussed.
Influencia del cambio climático en el turismo de nieve del Pirineo. Experiencia del proyecto de investigación NIVOPYR
Authors: Pons M. , López Moreno J. I. , Esteban P. , Macià S. , Gavaldà J. , García C. , Rosas-Casals M. , Jover E.
Published: October 2014

En los últimos años multitud de estudios han evidenciado y corroborado la existencia de un cambio climático global. A pesar de la existencia de una gran heterogeneidad regional en el grado y la temporalidad de los posibles impactos del cambio climático, cada vez se conocen mejor cuales pueden ser las tendencias futuras sobre posibles cambios en regímenes de temperatura y precipitaciones y, por lo tanto, en otros impactos indirectos sobre la Biosfera o la Criosfera. En este contexto, las áreas de montaña han sido identificadas como regiones especialmente vulnerables a los efectos del cambio climático y como zonas de gran interés para la detección y evaluación de los posibles impactos. Por otro lado, en las últimas décadas, el turismo de invierno, altamente sensible a los cambios en la meteorología y la disponibilidad de nieve, se ha convertido en una de las principales actividades económicas en muchas zonas de montaña y ha jugado un papel clave y fundamental como fuente de ingresos y desarrollo local. Un claro ejemplo es el caso de los Pirineos, una de las regiones europeas más importantes en lo que se refiere a turismo de invierno después de los Alpes.
La motivación principal del proyecto NIVOPYR, proyecto de investigación multinacional en el marco de la Comunidad de Trabajo de los Pirineos (CTP), es evaluar la posible influencia del cambio climático en la evolución del turismo de nieve, y más específicamente el esquí alpino, en esta región. Así, se han realizado diferentes tareas orientadas a integrar el conocimiento ya existente en los patrones presentes y futuros de las temperaturas, precipitaciones, cubierta de nieve y comportamiento de los esquiadores, desarrollar metodologías de análisis y obtener por primera vez datos objetivos para la región Pirenaica. De este modo, se ha obtenido tres perfiles diferentes de estaciones de esquí dependiendo de su vulnerabilidad frente al cambio climático. Un primer grupo de estaciones, identificado como altamente vulnerables, se vería afectado tanto por un escenario de cambio climático medio como por uno más intensivo y, por lo tanto, deberían contemplar la aplicación de medidas de adaptación estructurales, como una mayor desestacionalización y diversificación de su actividad turística. Las estaciones del segundo grupo, consideradas de climábaja vulnerabilidad, podrían seguir operando con medidas de adaptación técnicas bajo un escenario de cambio climático medio, pero no bajo un escenario de cambio climático más intenso. Finalmente, el tercer grupo, engloba las estaciones consideradas como resilientes. Estas estaciones, debido a una situación geográfica y socioeconómica privilegiada frente al resto de estaciones del Pirineo, se verían poco afectadas tanto por un escenario medio de cambio climático como por uno más intenso.
Improving Novice Programmers' Skills through Playability and Pattern Discovery
Authors: Barcelos Thiago Schumacher , Soto Roberto Muñoz , Silveira Ismar Frango
Published: October 2014

Game design and development has already been discussed as a viable, motivating alternative to introduce Computer Science concepts to young students. In this sense, it would be useful to obtain a deeper understanding of which skills could be developed in these activities and how such skills could be useful in future careers. This chapter presents the design and evaluation of a Game Building Workshop aimed at introducing the fundamentals of structured programming to students. The games produced by students during 12 weeks were evaluated and the results confronted with students' questions and comments made along the workshop meetings and a final interview. The results indicate that students explored novel programming concepts in order to add features that were not initially planned for the proposed games. These additional features solve playability issues that are highly influential to the experience of the students as game players. Students also reused previously applied solutions to solve similar problems that appeared in subsequent activities. This is an indication that students developed or exercised analogy and abstraction skills during the workshop activities.
Expanding the Knowledge Capability of Suppliers through Supplier Development Programs
Authors: Wu Chun-I
Published: October 2014

As firms increasingly outsource to focus on their core competencies, effective supplier development has become a major strategic decision in order to maintain a network of competent suppliers. Supplier development can be seen as a capability-enhancing activity that an organization undertakes to improve its suppliers' performance. This study conceptualizes supplier development as a knowledge-intensive and collaborative program, and explores how knowledge creation processes can be facilitated through different supplier development activities. A qualitative inquiry with a thematic analysis that focuses on five companies that are the suppliers of the largest motorcycle firm in Taiwan is presented in order to identify how different supplier development activities facilitate the knowledge creation process through the SECI modes and ba. The results show that these supplier development activities facilitate different types of knowledge conversion processes that can expand the knowledge capability of suppliers in a so-called center-satellite supply chain.
Absence of IFN-γ Increases Brain Pathology in Experimental Autoimmune Encephalomyelitis–Susceptible DRB1*0301.DQ8 HLA Transgenic Mice through Secretion of Proinflammatory Cytokine IL-17 and Induction of Pathogenic Monocytes/Microglia into the Central Nervous System
Authors: Mangalam Ashutosh K. , Luo Ningling , Luckey David , Papke Louisa , Hubbard Alyssa , Wussow Arika , Smart Michele , Giri Shailendra , Rodriguez Moses , David Chella
Published: October 2014

Multiple sclerosis is an inflammatory, demyelinating disease of the CNS of presumed autoimmune origin. Of all the genetic factors linked with multiple sclerosis, MHC class II molecules have the strongest association. Generation of HLA class II transgenic (Tg) mice has helped to elucidate the role of HLA class II genes in chronic inflammatory and demyelinating diseases. We have shown that the human HLA-DRB1*0301 gene predisposes to proteolipid protein (PLP)–induced experimental autoimmune encephalomyelitis (EAE), whereas HLA-DQβ1*0601 (DQ6) was resistant. We also showed that the DQ6 molecule protects from EAE in DRB1*0301.DQ6 double-Tg mice by producing anti-inflammatory IFN-γ. HLA-DQβ1*0302 (DQ8) Tg mice were also resistant to PLP91–110–induced EAE, but production of proinflammatory IL-17 exacerbated disease in DRB1*0301.DQ8 mice. To further confirm the role of IFN-γ in protection, we generated DRB1*0301.DQ8 mice lacking IFN-γ (DRB1*0301.DQ8.IFN-γ−/−). Immunization with PLP91–110 peptide caused atypical EAE in DRB1*0301.DQ8.IFN-γ−/− mice characterized by ataxia, spasticity, and dystonia, hallmarks of brain-specific disease. Severe brain-specific inflammation and demyelination in DRB1*0301.DQ8.IFN-γ−/− mice with minimal spinal cord pathology further confirmed brain-specific pathology. Atypical EAE in DRB1*0301.DQ8.IFN-γ−/− mice was associated with increased encephalitogenicity of CD4 T cells and their ability to produce greater levels of IL-17 and GM-CSF compared with DRB1*0301.DQ8 mice. Further, areas with demyelination showed increased presence of CD68+ inflammatory cells, suggesting an important role for monocytes/microglia in causing brain pathology. Thus, our study supports a protective role for IFN-γ in the demyelination of brain through downregulation of IL-17/GM-CSF and induction of neuroprotective factors in the brain by monocytes/microglial cells.
C4 Deficiency Is a Predisposing Factor for Streptococcus pneumoniae–Induced Autoantibody Production
Authors: Yammani Rama D. , Leyva Marcela A. , Jennings Ryan N. , Haas Karen M.
Published: October 2014

Reductions in C4 levels may predispose individuals to infection with encapsulated bacteria as well as autoimmunity. In this study, we examined the role C4 has in protection against Streptococcus pneumoniae–induced autoimmunity. Mild respiratory infection with serotype 19F pneumococci selectively induced systemic anti-dsDNA IgA production in naive C4−/− mice, but not in C3−/− or wild-type mice. Systemic challenge with virulent serotype 3 pneumococci also induced anti-dsDNA IgA production in immune C4−/− mice. Remarkably, pneumococcal polysaccharide (PPS) vaccination alone induced C4−/− mice to produce increased anti-dsDNA IgA levels that were maintained in some mice for months. These effects were most pronounced in female C4−/− mice. Importantly, immunization-induced increases in anti-dsDNA IgA levels were strongly associated with increased IgA deposition in kidneys. Cross-reactivity between pneumococcal Ags and dsDNA played a partial role in the induction of anti-dsDNA IgA, but a major role for PPS-associated TLR2 agonists was also revealed. Administration of the TLR2/4 antagonist, OxPAPC, at the time of PPS immunization completely blocked the production of anti-dsDNA IgA in C4−/− mice without suppressing PPS-specific Ab production. The TLR2 agonist, Pam3CSK4, similarly induced anti-dsDNA IgA production in C4−/− mice, which OxPAPC also prevented. LPS, a TLR4 agonist, had no effect. Pam3CSK4, but not LPS, also induced dsDNA-specific IgA production by C4−/− splenic IgA+ B cells in vitro, indicating that TLR2 agonists can stimulate autoantibody production via B cell–intrinsic mechanisms. Collectively, our results show an important role for C4 in suppressing autoantibody production elicited by cross-reactive Ags and TLR2 agonists associated with S. pneumoniae.
Adoptive Immunotherapy of Epithelial Ovarian Cancer with Vγ9Vδ2 T Cells, Potentiated by Liposomal Alendronic Acid
Authors: Parente-Pereira Ana C. , Shmeeda Hilary , Whilding Lynsey M. , Zambirinis Constantinos P. , Foster Julie , van der Stegen Sjoukje J. C. , Beatson Richard , Zabinski Tomasz , Brewig Nancy , Sosabowski Jane K. , Mather Stephen , Ghaem-Maghami Sadaf , Gabizon Alberto , Maher John
Published: October 2014

Adoptive immunotherapy using γδ T cells harnesses their natural role in tumor immunosurveillance. The efficacy of this approach is enhanced by aminobisphosphonates such as zoledronic acid and alendronic acid, both of which promote the accumulation of stimulatory phosphoantigens in target cells. However, the inefficient and nonselective uptake of these agents by tumor cells compromises the effective clinical exploitation of this principle. To overcome this, we have encapsulated aminobisphosphonates within liposomes. Expanded Vγ9Vδ2 T cells from patients and healthy donors displayed similar phenotype and destroyed autologous and immortalized ovarian tumor cells, following earlier pulsing with either free or liposome-encapsulated aminobisphosphonates. However, liposomal zoledronic acid proved highly toxic to SCID Beige mice. By contrast, the maximum tolerated dose of liposomal alendronic acid was 150-fold higher, rendering it much more suited to in vivo use. When injected into the peritoneal cavity, free and liposomal alendronic acid were both highly effective as sensitizing agents, enabling infused γδ T cells to promote the regression of established ovarian tumors by over one order of magnitude. Importantly however, liposomal alendronic acid proved markedly superior compared with free drug following i.v. delivery, exploiting the “enhanced permeability and retention effect” to render advanced tumors susceptible to γδ T cell–mediated shrinkage. Although folate targeting of liposomes enhanced the sensitization of folate receptor–α+ ovarian tumor cells in vitro, this did not confer further therapeutic advantage in vivo. These findings support the development of an immunotherapeutic approach for ovarian and other tumors in which adoptively infused γδ T cells are targeted using liposomal alendronic acid.
Co-expression Network Analysis of Human lncRNAs and Cancer Genes
Authors: Cogill Steven B. , Wang Liangjiang
Published: October 2014

We used gene co-expression network analysis to functionally annotate long noncoding RNAs (lncRNAs) and identify their potential cancer associations. The integrated microarray data set from our previous study was used to extract the expression profiles of 1,865 lncRNAs. Known cancer genes were compiled from the Catalogue of Somatic Mutations in Cancer and UniProt databases. Co-expression analysis identified a list of previously uncharacterized lncRNAs that showed significant correlation in expression with core cancer genes. To further annotate the lncRNAs, we performed a weighted gene co-expression network analysis, which resulted in 37 co-expression modules. Three biologically interesting modules were analyzed in depth. Two of the modules showed relatively high expression in blood and brain tissues, whereas the third module was found to be downregulated in blood cells. Hub lncRNA genes and enriched functional annotation terms were identified within the modules. The results suggest the utility of this approach as well as potential roles of uncharacterized lncRNAs in leukemia and neuroblastoma.
The Axis of Progression of Disease
Authors: Tartakoff Alan M. , Wu Di
Published: October 2014

Starting with genetic or environmental perturbations, disease progression can involve a linear sequence of changes within individual cells. More often, however, a labyrinth of branching consequences emanates from the initial events. How can one repair an entity so fine and so complex that its organization and functions are only partially known? How, given the many redundancies of metabolic pathways, can interventions be effective before the last redundant element has been irreversibly damaged? Since progression ultimately proceeds beyond a point of no return, therapeutic goals must target earlier events. A key goal is therefore to identify early changes of functional importance. Moreover, when several distinct genetic or environmental causes converge on a terminal phenotype, therapeutic strategies that focus on the shared features seem unlikely to be useful - precisely because the shared events lie relatively downstream along the axis of progression. We therefore describe experimental strategies that could lead to identification of early events, both for cancer and for other diseases.
The Association of Pre-Existing Left Atrial Fibrosis with Clinical Variables in Patients Referred for Catheter Ablation of Atrial Fibrillation
Authors: Dewire Jane , Khurram Irfan M. , Pashakhanloo Farhad , Spragg David , Marine Joseph E. , Berger Ronald D. , Ashikaga Hiroshi , Rickard John , Zimmerman Stefan L. , Zipunnikov Vadim , Calkins Hugh , Nazarian Saman
Published: October 2014

Introduction

Atrial fibrillation (AF) recurrence after ablation is associated with left atrial (LA) fibrosis on late gadolinium enhanced (LGE) magnetic resonance imaging (MRI). We sought to determine pre-ablation, clinical characteristics that associate with the extent of LA fibrosis in patients undergoing catheter ablation for AF.

Methods and Results

Consecutive patients presenting for catheter ablation of AF were enrolled and underwent LGE-MRI prior to initial AF ablation. The extent of fibrosis as a percentage of total LA myocardium was calculated in all patients prior to ablation. The cohort was divided into quartiles based on the percentage of fibrosis. Of 60 patients enrolled in the cohort, 13 had <5% fibrosis (Group 1), 15 had 5-7% fibrosis (Group 2), 17 had 8-13% fibrosis (Group 3), and 15 had 14-36% fibrosis (Group 4). The extent of LA fibrosis was positively associated with time in continuous AF, and the presence of persistent or longstanding persistent AF. However, no statistically significant difference was observed in the presence of comorbid conditions, age, BMI, LA volume, or family history of AF among the four groups. After adjusting for diabetes and hypertension in a multivariable linear regression model, paroxysmal AF remained independently and negatively associated with the extent of fibrosis (-4.0 ± 1.8, P = 0.034).

Conclusion

The extent of LA fibrosis in patients undergoing AF ablation is associated with AF type and time in continuous AF. Our results suggest that the presence and duration of AF are primary determinants of increased atrial LGE.
Diagnosis and Management of Valvular Aortic Stenosis
Authors: Czarny Matthew J. , Resar Jon R.
Published: October 2014

Valvular aortic stenosis (AS) is a progressive disease that affects 2% of the population aged 65 years or older. The major cause of valvular AS in adults is calcification and fibrosis of a previously normal tricuspid valve or a congenital bicuspid valve, with rheumatic AS being rare in the United States. Once established, the rate of progression of valvular AS is quite variable and impossible to predict for any particular patient. Symptoms of AS are generally insidious at onset, though development of any of the three cardinal symptoms of angina, syncope, or heart failure portends a poor prognosis. Management of symptomatic AS remains primarily surgical, though transcatheter aortic valve replacement (TAVR) is becoming an accepted alternative to surgical aortic valve replacement (SAVR) for patients at high or prohibitive operative risk.
Impact of D-Dimers on the Differential Diagnosis of Acute Chest Pain: Current Aspects besides the Widely Known
Authors: Hahne Kathrin , Lebiedz Pia , Breuckmann Frank
Published: October 2014

D-dimers are cleavage products of fibrin that occur during plasmin-mediated fibrinolysis of blood clots. In the emergency department, D-dimer measurement represents a valuable and cost-effective tool in the differential diagnosis of acute chest pain including the main life-threatening entities: acute coronary syndrome, pulmonary embolism, and acute aortic syndrome. Whereas the diagnostic and prognostic values of D-dimer testing in acute coronary syndrome is of less priority, increases of D-dimers are frequently found in venous thromboembolism and acute aortic syndromes, especially acute aortic dissection. As to the high negative predictive value of D-dimer in those disorders, patients with low to intermediate pretest probability may profit in terms of less necessity of further non-invasive or even invasive imaging, simultaneously reducing potential complications and healthcare-related costs. However, because of the low specificity of the different D-dimer tests in contrast to its frequent usage, adequate interpretation is required. Age-related adjustment of D-dimer levels may be used to increase its diagnostic power.
Insecticides and Bio-insecticides Modulate the Glutathione-related Antioxidant Defense System of Cowpea Storage Bruchid (Callosobruchus maculatus)
Authors: Kolawole Ayodele O. , Kolawole Adejoke N.
Published: October 2014

The possible cellular involvements of cowpea storage bruchid ( Callosobruchus maculatus (Fab.) [Coleoptera: Chrysomelidae]) glutathione and its related enzymes system in the cellular defense against insecticides (Cypermethrin and λ-cyhalothrin) and bio-insecticides (ethanolic extract of Tithonia diversifolia, Cyperus rotundus, Hyptis suavolens leaves, and Jatropha curcas seed) were investigated. The results showed that the effect of insecticides and bio-insecticides on the C. maculatus is a function of oxidative and nitrosative stresses generated in vivo. A significant ( p < 0.05) increase in carbonyl protein (CP) and lipid peroxidation (LPO) contents in bio-insecticides and insecticides exposed groups compared to the control indicates the extent of vital organs damage. These stresses caused similar and significant increase of glutathione peroxidase and glutathione synthetase in response to insecticides and bio-insecticide exposure in a dose-dependent manner. There was no post-translational modification of glutathione transferases expression induced. The alterations of the insect glutathione-dependent antioxidant enzyme activities reflect the presence of a functional defense mechanism against the oxidative and nitrosative stress and are related firmly to the glutathione demands and metabolism but appear inadequate by the significant reduction in glutathione reductase (GR) activity to prevent the damages. Exogenous application of reduced glutathione (GSH), to complement the in vivo demand, could not protect against the onslaught.
Rezensionen
Authors: Schneebeli H. R.
Published: October 2014

Rezension zu:
H. Walser:
Geometrische Miniaturen. Figuren – Muster – Symmetrien
. 98 Seiten, 14.50 EUR. Edition am Gutenbergplatz, Leipzig, 2011, EAGLE 042; ISBN 978-3-937219-42-4.
Use of Instructor-Produced YouTube® Videos to Supplement Manual Skills Training in Occupational Therapy Education
Authors: McAlister Robert B.
Published: October 2014

An ongoing challenge to occupational therapy educators is how to provide resources and strategies that best assist students in learning, retaining, and replicating protocols in clinical manual assessment. This pilot survey study explored how 43 first-year master’s of occupational therapy students enrolled in a kinesiology course perceived the value of implementing instructor-produced YouTube® videos of in-class assessment demonstrations. The videos, taken on a smartphone, were uploaded to a private YouTube URL created by the instructor and then linked to a pre-established Moodle learning platform. By the end of the 6-wk course, students had registered 2,573 views averaging 60 views per student. Postcourse mixed survey results revealed students perceived that the videos improved the quality of the course, increased their level of engagement and learning, and boosted confidence in their manual skills. Survey results also found that students correlated the instructor’s willingness to develop online videos with a commitment to student learning.
Numerical analysis of the primary processes controlling oxygen dynamics on the Louisiana Shelf
Authors: Yu L. , Fennel K. , Laurent A. , Murrell M. C. , Lehrter J. C.
Published: October 2014

Abstract. The Louisiana shelf in the northern Gulf of Mexico receives large amounts of freshwater and nutrients from the Mississippi/Atchafalaya River system. These river inputs contribute to widespread bottom-water hypoxia every summer. In this study, we use a physical-biogeochemical model that explicitly simulates oxygen sources and sinks on the Louisiana shelf to identify the key mechanisms controlling hypoxia development. First, we validate the model simulation against observed dissolved oxygen concentrations, primary production, water column respiration, and sediment oxygen consumption. In the model simulation, heterotrophy is prevalent in shelf waters throughout the year except near the mouths of the Mississippi and Atchafalaya Rivers where primary production exceeds respiratory oxygen consumption during June and July. During this time, efflux of oxygen to the atmosphere, driven by photosynthesis and surface warming, becomes a significant oxygen sink while the well-developed pycnocline isolates autotrophic surface waters from the heterotrophic and hypoxic waters below. A substantial fraction of primary production occurs below the pycnocline in summer. We investigate whether this primary production below the pycnocline is mitigating the development of hypoxic conditions with the help of a sensitivity experiment where we disable biological processes in the water column (i.e. primary production and water column respiration). In this experiment below-pycnocline primary production reduces the spatial extent of hypoxic bottom waters only slightly. Our results suggest that the combination of physical processes and sediment oxygen consumption largely determine the spatial extent and dynamics of hypoxia on the Louisiana shelf.
Audit of the global carbon budget: estimate errors and their impact on uptake uncertainty
Authors: Ballantyne A. P. , Andres R. , Houghton R. , Stocker B. D. , Wanninkhof R. , Anderegg W. , Cooper L. A. , DeGrandpre M. , Tans P. P. , Miller J. C. , Alden C. , White J. W. C.
Published: October 2014

Abstract. Over the last 5 decades monitoring systems have been developed to detect changes in the accumulation of C in the atmosphere, ocean, and land; however, our ability to detect changes in the behavior of the global C cycle is still hindered by measurement and estimate errors. Here we present a rigorous and flexible framework for assessing the temporal and spatial components of estimate error and their impact on uncertainty in net C uptake by the biosphere. We present a novel approach for incorporating temporally correlated random error into the error structure of emission estimates. Based on this approach, we conclude that the 2 σ error of the atmospheric growth rate has decreased from 1.2 Pg C yr−1 in the 1960s to 0.3 Pg C yr−1 in the 2000s, leading to a ~20% reduction in the over-all uncertainty of net global C uptake by the biosphere. While fossil fuel emissions have increased by a factor of 4 over the last 5 decades, 2 σ errors in fossil fuel emissions due to national reporting errors and differences in energy reporting practices have increased from 0.3 Pg C yr−1 in the 1960s to almost 1.0 Pg C yr−1 during the 2000s. At the same time land use emissions have declined slightly over the last 5 decades, but their relative errors remain high. Notably, errors associated with fossil fuel emissions have come to dominate uncertainty in the global C budget and are now comparable to the total emissions from land use, thus efforts to reduce errors in fossil fuel emissions are necessary. Given all the major sources of error in the global C budget that we could identify, we are 93% confident that C uptake has increased and 97% confident that C uptake by the terrestrial biosphere has increased over the last 5 decades. Although the persistence of future C sinks remains unknown and some ecosystem services may be compromised by this continued C uptake (e.g. ocean acidification), it is clear that arguably the greatest ecosystem service currently provided by the biosphere is the continued removal of approximately half of atmospheric CO2 emissions from the atmosphere.