bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with prevalence of anxiety disorder among nurses working in Covid-19 isolation centers in Lagos, Nigeria.
Authors:   Department of Nursing Science, Babcock University., Rasheed Olusegun , Aina Oyeniyi ,   Department of Nursing Science, Babcock University.
Published: January 2024

The unprecedented demands for services offered by nurses emerging from the COVID-19 pandemic placed much mental health pressure and physical exhaustion on nurses in the various isolation centers. This study estimated prevalence of anxiety disorder and examined associated factors among nurses working in COVID-19 isolation centers in Lagos, Nigeria. A cross-sectional study design was adopted with purposive sampling method selecting two isolation centers in Lagos of total enumeration sample size of 75 nurses was conducted. Data was collected with a validated structured questionnaire and analyzed with IBM SPSS version 25. Fisher’s Exact Test and multivariate logistic regressions were conducted to determine the predictors of anxiety disorders at 5% level of significance and 95% CI. The results showed the mean age of nurses m=37.6 + 10.2 years, while 39.7% of nurses reported having mild to severe anxiety disorder. The age, gender, marital status and living with vulnerable persons were not significantly associated with the anxiety disorder with p > 0.05. The odds of anxiety disorder were 2.3 times more likely for nurses having regular contact with COVID-19 patients with symptoms compared to nurses who did not (OR=2.3, 95% CI= 4.338 to 41.962, p=0.010). In conclusion, more than one-third of nurses developed mild to severe anxiety disorder. A psychological intervention program is recommended to support the affected nurses. Keywords: anxiety disorder, coronavirus, isolation center, nurse, prevalence.
Determinants of Healthcare-Seeking Behavior for Work-related Musculoskeletal Disorders among Artisans in Alimosho Local Government Area Lagos State, Nigeria
Authors:   Department of Public Health, Babcock University., Adeoye Oluwabukola , Dangana Jonathan ,   Department of Public Health, Babcock University.
Published: January 2024

Musculoskeletal disorders are work-related injuries that affect artisans in their working years. Studies have established the healthcare-seeking behavior of artisans as poor and associated factors understudied. Understanding the factors that determine healthcare-seeking behavior of this population would help improve their productivity, quality of life and skilled healthcare-seeking behavior. This study therefore investigated factors associated with healthcare-seeking behavior of artisans in Alimosho LGA, Lagos State. A cross-sectional study design using multi-stage sampling was utilized, 427 respondents were selected purposively. A validated, structured and interviewer--administered questionnaire with Cronbach alpha coefficient of 0.79 was used in data collection. Data was analyzed using IBM SPSS 23.0 to generate descriptive and inferential statistics at P < 0.05 level of significance. The mean age of respondents was 38.5 ± 11.18 years. A high level of predisposing factors, low levels of reinforcing factor, enabling factor and poor healthcare-seeking behavior (16.95 ± 2.94, 5.86 ± 2.64, 6.39 ± 3.40 and 7.34 ± 2.40 respectively) was observed among them. There was a significant relationship (p = 0.000) between each independent variable and healthcare-seeking behavior (r = 0.20, 0.26, and 0.30). The most significant predictor of healthcare seeking behavior of the artisans was the enabling factor (ß = 0.16; t = 4.66). The predisposing, reinforcing and enabling factors were determinants of healthcare-seeking behavior among the artisans in this study. It is recommended that these factors be employed in the campaign of health improvement by public health professionals in order to improve healthcare-seeking behavior of artisans. Keywords: Work-related musculoskeletal disorders, Determinants, Artisans, Healthcare-seeking behaviour, Alimosho.
Homeschooling – the idea and one of its forms of realization on the example of the activities of the ParoKrok Foundation
Authors: Sobczak Anna
Published: January 2024

Wprowadzenie. Edukacja domowa stanowi alternatywę dla kształcenia szkolnego. Jej fundamentalnym założeniem jest nieuczęszczanie dzieci na lekcje w szkole i nauczanie ich przez rodziców w domu. Obecnie można wskazać na szeroki wachlarz możliwości realizowania edukacji domowej. Cel. Celem artykułu jest zwrócenie uwagi na różnorodne formy, jakie dzisiaj może przybierać edukacja domowa dzieci, i opisanie działalności edukacyjnej jednej z poznańskich fundacji, która w ramach tworzonych „mikroklas” prowadzi zajęcia dla dzieci realizujących obowiązek szkolny poza szkołą. Materiał i metody. W pracy wykorzystano metodę analizy oraz syntezy źródeł literaturowych. Wyniki. Idea edukacji poza szkołą zyskuje wśród rodziców na popularności, a postęp technologiczny oraz zmiany społeczne pozwalają na różnorodne formy jej realizowania. Doskonałym przykładem jest działalność Fundacji ParoKrok, która prowadzi zajęcia dla dzieci w edukacji domowej na poziomie szkoły podstawowej zgodnie z podstawą programową Ministerstwa Edukacji i Nauki. Organizacja ta realizuje edukację przygotowującą dzieci do rocznych egzaminów klasyfikacyjnych, wykorzystując metodę projektową, polegającą na łączeniu elementów różnych przedmiotów. Stawia także na relacje i rozwój zainteresowań uczniów. Wnioski. Edukacja domowa, na którą coraz częściej decydują się rodzice, może przynieść wiele korzyści, szczególnie dla dzieci i ich osiągnięć. Dlatego też warto poszerzać społeczny
i polityczny dyskurs o edukacji domowej. Organizacje pozarządowe i ich odpowiednie działania mogą być wsparciem dla rodzin w edukacji domowej. Projekt edukacyjny Fundacji ParoKrok, skierowany do uczniów w edukacji domowej, stanowi tego ciekawy i wartościowy przykład.
Narratives in family transmission. Threads of verbal folklore in regional literature on the example of one of the volumes of the series "Jako downi bywało"
Authors: Przybyła-Dumin Agnieszka
Published: January 2024

Cel. Celem niniejszego artykułu jest omówienie wybranych wątków folkloru słownego wykorzystanego w opracowaniu mieszkanki Górnego Śląska opublikowanym w ramach serii wydawniczej „Jako downi bywało” przez muzeum „Górnośląski Park Etnograficzny w Chorzowie”. W opracowaniu zaprezentowane zostały wybrane gatunki, okoliczności, w jakich są wywoływane, oraz funkcje, jakie pełnią.
Materiały i metody. Analiza tekstu źródłowego – publikacji z serii „Jako downi bywało” pt. Najmilsze zimowe wieczory. Piyrzi furgało, berōw sie słuchało autorstwa Anny Stronczek. Wyniki i wnioski. Książka Najmilsze zimowe wieczory stanowi istotny wkład w zachowanie niematerialnego dziedzictwa kulturowego Górnego Śląska. Opisy tradycji kultywowanych we wspólnocie, do której należy autorka, oraz znajdujący się w przekazie folklor słowny są istotnym wyrazem ich światopoglądu, samo zaś dzieło jest dla badaczy cennym źródłem treści kultury regionalnej. Stanowi też interesujące i wartościowe źródło do projektowania scenariuszy z zakresu edukacji regionalnej czy też wsparcie dla przekazu rodzinnego w sytuacji braku starszego pokolenia lub zanikającej z innych przyczyn trans-misji. Folklor stanowi istotny czynnik budujący obraz świata i człowieka, niesie wartości podzielane przez zbiorowość i społecznie pożądany model człowieka, przez co daje możliwość kształtowania osobowości członków wspólnoty. Dodatkowy walor w postaci prezentacji wątków daje wgląd w ich „naturalny” przekaz i wpisuje je we właściwy kontekst, co przyczynia się do wzbogacenia ich treści o pozawerbalnie znaczenia.
Single-cell data revealed CD14-type and FCGR3A-type macrophages and relevant prognostic factors for predicting immunotherapy and prognosis in stomach adenocarcinoma
Authors: Li Mengling , Lu Ming , Li Jun , Gui Qingqing , Xia Yibin , Lu Chao , Shu Hongchun
Published: January 2024

Background

Stomach adenocarcinoma (STAD) exhibits profound tumor heterogeneity and represents a great therapeutic challenge. Single-cell sequencing technology is a powerful tool to identify characteristic cell types.

Methods

Single-cell sequencing data (scRNA-seq) GSE167297 and bulk RNA-seq data from TCGA, GTEx, GSE26901 and GSE15459 database were included in this study. By downscaling and annotating the cellular data in scRNA-seq, critical cell types in tumor progression were identified by AUCell score. Relevant gene modules were then identified by weighted gene co-expression network analysis (WGCNA). A prognostic scoring system was constructed by identifying prognostic factors in STAD by Least absolute shrinkage and selection operator (LASSO) COX model. The prognosis and model performance in the RiskScore groups were measured by Kaplan-Meier (K-M) curves and Receiver operating characteristic (ROC) curves. Nomogram was drawn based on RiskScore and prognosis-related clinical factors. In addition, we evaluated patient’s feedback on immunotherapy in the RiskScore groups by TIMER, ESTIMATE and TIDE analysis. Finally, the expression levels of prognostic factors were verified in gastric cancer cell lines (MKN7 and MKN28) and human normal gastric mucosal epithelial cells (GES-1), and the effects of prognostic factors on the viability of gastric cancer cells were examined by the CCK8 assay and cell cycle.

Results

scRNA-seq analysis revealed that 11 cell types were identified, and macrophages exhibited relatively higher AUCell scores and specifically expressed CD14 and FCGR3A. High macrophage scores worsened the prognosis of STAD patients. We intersected the specifically expressed genes in macrophages subgroups (670) and macrophage module genes (2,360) obtained from WGCNA analysis. Among 86 common genes, seven prognostic factors (RGS2, GNAI2, ANXA5, MARCKS, CD36, NRP1 and PDE4A) were identified and composed a RiskScore model. Patients in low Risk group showed a better survival advantage. Nomogram also provided a favorable prediction for survival at 1, 3 and 5 years in STAD patients. Besides, we found positive feedback to immunotherapy in patients with low RiskScore. The expression tendency of the seven prognostic factors in MKN7 and MKN28 was consistent with that in the RNA-seq data in addition to comparison of protein expression levels in the public HPA (The Human Protein Atlas) database. Further functional exploration disclosed that MARCKS was an important prognostic factor in regulating cell viability in STAD.

Conclusion

This study preliminary uncovered a single cell atlas for STAD patients, and Macrophages relevant gene signature and nomogram displayed favorable immunotherapy and prognostic prediction ability. Collectively, our work provides a new insight into the molecular mechanisms and therapeutic approach for LUAD patients.
Caracterización biomecánica del proceso de NETosis en suspensión
Authors:   , Morales Camilo Nicole
Published: January 2024

Las NETs son fibras de cromatina descondensada que forman una red compuesta mayoritariamente por ADN e histonas y proteínas antimicrobiales, consecuencia del mecanismo de muerte celular programada llamada NETosis, para la generación de una barrera física que previene la diseminación de patógenos. La NETosis es un proceso dinámico que implica transformaciones significativas en el citoesqueleto y el núcleo celular, y con ello, cambios significativos en las propiedades mecánicas celulares; sin embargo, la caracterización de este proceso en un contexto cercano al fisiológico no ha sido abordado. Este trabajo busca estudiar la biomecánica del proceso de NETosis en suspensión utilizando una aproximación interdisciplinaria. Para medir los cambios morforeológicos del proceso de NETosis en flujo se adaptó la metodología de RT-DC y determinó el módulo de Young (elasticidad) de los neutrófilos estimulados. El RT-DC corroboró que la NETosis inducida por PMA es independiente al proceso de adhesión, en condiciones de flujo. Así también, el análisis de los gráficos área versus deformación obtenidos por el RT-DC, permitió la clasificación y caracterización de subpoblaciones celulares, y comprobar la generación de NETs en suspensión. Finalmente, la caracterización morforeológica de estos neutrófilos muestran un aumento significativo en su tamaño celular (>30 µm2) y cambios de elasticidad con una fase inicial “rápida” de aumento en la rigidez y luego una fase “lenta” de disminución de la rigidez. Este estudio proporcionó evidencia necesaria para relacionar las características biomecánicas de la NETosis con el mecanismo molecular y la temporalidad descrita para este proceso, en un contexto cercano al fisiológico.
Principales dudas en torno a la vacunación de población chilena reticente a la vacunación según nivel educacional
Authors:   , Hetreau Bernardita
Published: January 2024

Introducción: En los últimos años ha crecido exponencialmente la cantidad de personas en el mundo y en Chile que se identifican como antivacunas o reticentes a la vacunación, lo que constituye un peligro para la salud pública. Para hacer frente a este problema y evitar la proliferación de grupos antivacunas en Chile es necesario comprender a cabalidad cuáles son los principales argumentos de personas antivacunas o reticentes a la vacunación para no desear vacunarse, así como cómo se distribuye este pensamiento en distintos segmentos de la población, considerando que esta no es una población homogénea. Objetivos: Identificar las principales dudas en torno a la vacunación de población reticente a la vacunación chilena según nivel educacional. Material y métodos: Estudio cualitativo en el cual se realizaron 3 grupos de discusión con población residente en Chile que se identifique como antivacuna o reticente a la vacunación. Los segmentos en los que se dividen los grupos de discusión son: Educación escolar incompleta; Educación media completa, técnica incompleta o completa o educación universitaria incompleta; y Educación universitaria completa y/o con estudios de postgrado. Resultados: Existen argumentos transversales a todos los diferentes niveles educacionales. Los argumentos para rechazar la vacunación más esgrimidos en los grupos con más años de escolaridad son los referidos a que sea una vacuna nueva y experimental, la efectividad de la vacuna y la relevancia del sistema inmune. En el grupo con menos años de escolaridad tuvieron más relevancia los argumentos de referencia a autoridades, desorden en la implementación de la vacuna, vacuna creada artificialmente y las malas experiencias en salud. También se encontró que existe en esta población un grado diverso de aceptación a vacunas que no son para el Covid-19, que hay distintos procesos de búsqueda de información según los años de escolaridad y que en algunos hay un fuerte grado de identificación identitaria con el movimiento de rechazo a la vacunación. Discusión y Conclusiones: El nivel educacional incide en los argumentos para rechazar la vacunación en Chile, por lo que es necesario elaborar estrategias comunicativas dirigidas específicamente a cada grupo para que sean más efectivas. Es importante responder las dudas sobre la vacunación de algunas personas antes de que su pensamiento evolucione hacia uno más extremo. Además, hay que considerar la influencia de factores no relacionados a la lógica como lo pueden ser los elementos identitarios que pueden operar al momento de adscribir a un movimiento que rechaza la vacunación. También hay que formar a los profesionales de la salud para mejorar la comunicación sobre las vacunas con los pacientes.
No more Frayed Ends – A Technique for Trimming the Uneven Ends of Ruptured Flexor Tendons Prior to Repair
Authors: WATTS A. M. I. , HERAS-PALOU C.
Published: June 2003

We describe a technique for the accurate and conservative debridement of the ends of divided flexor tendons. We have found this technique particularly useful for the secondary repair of tendons after re-rupture.
The minimum variance hedge and the bankruptcy risk of the firm
Authors: Hahnenstein Lutz , Röder Klaus
Published: June 2003

In this paper, we analyze the influence of hedging with forward contracts on the firm's probability of bankruptcy (POB). The minimization of this probability can serve as a substitute for the maximization of shareholders' wealth. It is shown that the popular minimum variance hedge is generally neither necessary nor sufficient for the minimization of the firm's POB. Moreover, our model suggests a correction of the widespread view that a reduction in the variance of the future value of the firm is inevitably accompanied by a reduction in its default risk. We derive an analytical solution for the variance‐minimizing hedge ratio of a firm exposed to both input and output price uncertainty that takes into account the issue of correlation. Based on this solution, we provide a graphical analysis to prove our claim that there is a fundamental difference between hedging policies focused on bankruptcy risk and those following conventional wisdom even if positive correlation constitutes a “natural” hedge.
Heparan Sulfate Proteoglycans Initiate Dengue Virus Infection of Hepatocytes
Authors: Hilgard Philip , Stockert Richard
Published: June 2003

Dengue viruses (DEN) cause a broad spectrum of clinical manifestations including potentially life–threatening conditions such as hemorrhagic shock syndrome and less frequently acute hepatitis with liver failure and encephalopathy. In addition, dengue viruses provide a potential model to understand the initiation of hepatocyte infection by the structurally closely related hepatitis C virus (HCV), because this virus at present cannot be grown in cell culture. Although the initial steps of viral infection are a critical determinant of tissue tropism and therefore pathogenesis, little is known about the molecular basis of binding and endocytic trafficking of DEN or of any other flavivirus. Our studies revealed that binding of radiolabeled DEN to the human hepatoma cell line HuH–7 was strictly pH dependent and substantially inhibitable by the glycosaminoglycan heparin. Ligand–blot analysis, performed as a viral overlay assay, showed two heparan sulfate (HS) containing cell–surface binding proteins resolving at 33 and 37 kd. Based on the sensitivity of unprotected virus and the viral binding site on the cell surface to trypsin, viral internalization was quantified as an increase in trypsin protected virus over time. Virus trafficking to the site of degradation was inhibited by pH dissociation of the clathrin coat and dependent on IP3–mediated homotypic endosomal fusion. These findings confirm the hypothesis that binding and internalization of DEN by hepatocytes are mediated primarily by HS containing proteoglycans and suggest that flaviviruses traffic the major clathrin–dependent endocytic pathway during infection.
Association of Amino Acid Sequence in the Pkr–Eif2 Phosphorylation Homology Domain and Response to Interferon Therapy
Authors: Chayama Kazuaki , Suzuki Fumitaka , Tsubota Akihito , Kobayashi Masahiro , Arase Yasuji , Saitoh Satoshi , Suzuki Yoshiyuki , Murashima Naoya , Ikeda Kenji , Takahashi Norihiko , Kinoshita Moritoshi , Kumada Hiromitsu
Published: June 2003

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are well known predictive factors of poor response to interferon (IFN) therapy. In addition, a sparsity of amino acid substitutions in the interferon sensitivity determining region (ISDR) is also predictive of a poor response to IFN in patients with genotype 1b, although this issue is still controversial. Recently, a 12 amino acid domain in the E2 protein of HCV (PKR–eIF2 α phosphorylation homology domain [PePHD]) has been reported to bind with and block the virus replication inhibition ability of PKR, suggesting that the interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of IFN. To clarify the significance of amino–acid sequences in this domain in predicting the effect of IFN therapy, we analyzed 82 patients with genotype 1b. Eleven patients (13.4%) responded to treatment whereas the remaining 71 patients (86.6%) were nonresponders. Multivariate analysis showed that only HCV load and amino–acid substitutions in the ISDR were predictive of sustained response to IFN. Amino–acid substitutions in the PePHD were detected in only eight of 82 patients (9.8%), and did not correlate with the therapeutic effect of IFN. However, amino–acid-sequence analyses of quasispecies before and after 1 week of IFN therapy showed elimination of clones with substitutions in this domain. Our results suggest that amino–acid sequences of the PePHD domain may be related to viral resistance to IFN but do not predict the outcome of IFN therapy as amino–acid substitutions in this domain are rare.
Utility of standard nutritional parameters in detecting body cell mass depletion in patients with end-stage liver disease
Authors: Figueiredo Fatima A. , Dickson Rolland E. , Pasha Tousif M. , Porayko Michael K. , Therneau Terry M. , Malinchoc Michael , DiCecco Sara R. , Francisco-Ziller Nickie M. , Kasparova Pavla , Charlton Michael R.
Published: June 2003

Protein-calorie malnutrition, best measured by body cell mass (BCM) depletion, has been associated with adverse outcomes in patients with end-stage liver disease. We prospectively measured BCM and multiple standard nutritional parameters in patients with end-stage liver disease to determine which, if any, of the traditionally measured nutritional parameters correlate with BCM. A detailed nutritional assessment, including BCM analysis, subjective global assessment, anthropometry, handgrip dynamometry, laboratory tests, and body composition measured by dual-energy X-ray absorptiometry was performed in 69 sequential patients awaiting liver transplantation. The frequency of abnormalities of specific parameters of nutritional status varied between 19% and 99%. Most of the commonly measured parameters of nutritional status correlated poorly with BCM. Patients with depleted BCM (lowest quartile for sex) had midarm circumference (P < .01), arm-muscle circumference (P < .001), handgrip strength (P < .001), blood urea nitrogen (P < .01), and creatinine (P < .01) values less than those for patients with greater BCM (highest 3 quartiles for sex). In multivariate analysis, arm-muscle circumference and handgrip strength were the best predictors of BCM. The combined criteria of handgrip strength less than 30 kg and arm-muscle circumference less than 23 cm have a sensitivity of 94% and a negative predictive value of 97% in identifying patients with depleted BCM. Although abnormalities of nutritional parameters are highly prevalent among patients with end-stage liver disease, most parameters of nutritional status do not correlate with BCM. In patients with end-stage liver disease, arm-muscle circumference and handgrip strength are the most sensitive markers of BCM depletion.
Spontaneous clearance of hepatitis C virus infection post-liver transplantation is associated with rapidly changing quasispecies: A single case report
Authors: Doughty Alison L. , Zekry Amany , Spencer Jenean D. , Turhan Seven , Painter Dorothy , McCaughan Geoffrey W.
Published: June 2003

Hepatitis C virus (HCV) clearance post-liver transplantation is uncommon. This is a case report of a patient who, after liver transplantation, developed cholestatic hepatitis characterized by severe graft dysfunction, in conjunction with high viral load. This was, however, followed by viral clearance and normalization of allograft function. The clinical features of this case and the quasispecies patterns during the illness and the clearance periods are described. In addition, management implications in terms of immunosuppressive therapy are discussed.
Cytadherence-Deficient Mutants of
Mycoplasma gallisepticum
Generated by Transposon Mutagenesis
Authors: Mudahi-Orenstein Sigalit , Levisohn Sharon , Geary Steven J. , Yogev David
Published: June 2003

Cytadherence-related molecules of
Mycoplasma gallisepticum
strain R-low were identified by Tn
4001
transposon mutagenesis with the hemadsorption (HA) assay as an indicator for cytadherence. Three Gm
r
HA-negative (HA
−
) colonies displaying a stable HA
−
phenotype through several successive generations in which gentamicin selection was maintained were isolated from four independent transformation experiments and characterized. Southern blot analysis showed that the transposon was inserted as a single copy within the genome of each of the HA
−
mutants, suggesting that the transposon insertion was directly responsible for their inability to attach to erythrocytes. Sequence analysis of the transposon insertion sites revealed that in two mutants, the transposon was inserted at two distinct sites within the
gapA
structural gene. In the third mutant, the insertion was mapped within the
crmA
gene, which is located immediately downstream of the
gapA
gene as part of the same operon. In vitro attachment experiments with the MRC-5 human lung fibroblast cell line showed that the cytadherence capabilities of the HA
−
mutants were less than 25% those of original strain R. Experimental infection of chickens, the natural host of
M
.
gallisepticum
, with each of the three mutants demonstrated significantly impaired colonization and host responses. These data demonstrate conclusively the role of both GapA and CrmA proteins in the adherence of
M
.
gallisepticum
to host cells in model systems and in vivo colonization. Furthermore, these results underscore the relevance of in vitro cytadherence model systems for studying the pathogenesis of natural infections in chickens.
Major Surface Protein 2 of
Anaplasma phagocytophilum
Facilitates Adherence to Granulocytes
Authors: Park Jinho , Choi Kyoung Seong , Dumler J. Stephen
Published: June 2003

Anaplasma phagocytophilum
is an obligate intracellular bacterium that infects myeloid cells in the mammalian host. Msp2 (p44) is the major immunodominant outer-membrane protein of these bacteria. We hypothesized that Msp2 acts as an adhesin for
A. phagocytophilum
entry into granulocytes. This potential role was investigated by blocking binding with Msp2 monoclonal antibodies and by antagonizing binding and propagation with recombinant Msp2 (rMsp2) in vitro. With HL-60 cells, fresh human peripheral blood neutrophils, and a cell line devoid of the fucosylated platelet selectin glycoprotein ligand 1 (PSGL-1) receptor for
A. phagocytophilum
or one that was transfected to express this ligand, Msp2 monoclonal antibody and rMsp2 used as the antagonist caused concentration-dependent reductions in bacterial adhesion (
P
< 0.007 and
P
< 0.02, respectively) and propagation (
P
< 0.05 and
P
< 0.001), although inhibition of adhesion or propagation was moderate and incomplete. Likewise, rMsp2 bound to surfaces of the transfected cell at a level similar to that of extracellular
A. phagocytophilum
and significantly (
P
< 0.05) beyond that of nontransfected cells. Moreover, a dose-dependent reduction (
P
< 0.019) in PSGL-1 monoclonal antibody binding to HL-60 cells was elicited with rMsp2. We conclude that Msp2s of
A. phagocytophilum
are involved in bacterial adhesion to ligands on host myeloid cells before intracellular infection.
Synthesis of Melanin-Like Pigments by
Sporothrix schenckii
In Vitro and during Mammalian Infection
Authors: Morris-Jones Rachael , Youngchim Sirida , Gomez Beatriz L. , Aisen Phil , Hay Roderick J. , Nosanchuk Joshua D. , Casadevall Arturo , Hamilton Andrew J.
Published: June 2003

Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen
Sporothrix schenckii
produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells.
S. schenckii
grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from
S. schenckii
yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with
S. schenckii
contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that
S. schenckii
conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis.
Soluble Extracts fromHelicobacter pyloriInduce Dome Formation in Polarized Intestinal Epithelial Monolayers in a Laminin-Dependent Manner
Authors: Terrés A. M. , Windle H. J. , Ardini E. , Kelleher D. P.
Published: June 2003

Helicobacter pyloricolonizes the stomach at the interface between the mucus layer and the apical pole of gastric epithelial cells. A number of secreted and shed products from the bacteria, such as proteins and lipopolysaccharide, are likely to have a role in the pathogenesis at the epithelial level. To determine the physiological response of transporting polarized epithelia to released soluble factors from the bacterium, we used the T84 cell line. Monolayers of T84 cells were exposed to soluble extracts fromH. pylori.The extracts induced rapid “dome” formation as well as an immediate decrease in transepithelial electrical resistance. Domes are fluid-filled blister-like structures unique to polarized epithelia. Their formation has been linked to sodium-transporting events as well as to diminished adherence of the cells to the substrate.H. pylori-induced dome formation in T84 monolayers was exacerbated by amiloride and inhibited by ouabain. Furthermore, it was associated with changes in the expression of the laminin binding α6β4 integrin and the 67-kDa laminin receptor. Domes formed primarily on laminin-coated filters, rather than on fibronectin or collagen matrices, and their formation was inhibited by preincubating the bacterial extract with soluble laminin. This effect was specific toH. pyloriand independent of the urease, vacA, cagA, and Lewis phenotype of the strains. These data indicate that released elements fromH. pylorican alter the physiological balance and integrity of the epithelium in the absence of an underlying immune response.
Engaging the Abyss: A Mis-Take of Opportunity?
Authors: Mitchell Gail J. , Bunkers Sandra Schmidt
Published: June 2003

There are occasions when persons find themselves faced with a difficult choice to be with one or more persons as they live intense experiences that often involve pain and suffering. It is proposed in this column that the experience of choosing to be with others during these times calls forth a risking of self. That fleeting moment when people choose to engage with others or to turn away from that opportunity is explored through personal experience and as portrayed in poetry and film. The authors use the metaphor of an abyss to explore the lived experience of risking being with the truth of human connectedness. It is suggested that nurses know the abyss and that they have opportunities to be with persons as they live truth in human becoming.
Peripheral targets of centrally located putative accessory neurons of MRO in the isopodLigia exotica
Authors: Hama Noriyuki , Okada Yoshinori , Pollák Edit , Molnár László , Niida Akiyoshi
Published: June 2003

The three centrally located putative accessory neurons of the muscle receptor organ (MRO) of the isopod Ligia exotica were identified to the third segmental nerve (N3) of the thoracic ganglion by backfilling with Lucifer Yellow. These neurons were then studied intracellularly and extracellularly to determine whether they suppressed the stretch-activated responses of thoracic stretch receptors. Intracellular injection of depolarizing currents into these three putative accessory neurons revealed that only neuron #3 had an inhibitory effect, suggesting that it is an inhibitory accessory neuron related to thoracic stretch receptors. We searched for the peripheral targets of neurons #1 and #2 by intracellular filling with Lucifer Yellow or by recording of junctional potentials in extensor muscles,and show that they are motor neurons that innervate the deep extensor and superficial extensor muscles, respectively.
Probing the limits to muscle-powered accelerations: lessons from jumping bullfrogs
Authors: Roberts Thomas J. , Marsh Richard L.
Published: June 2003

The function of many muscles during natural movements is to accelerate a mass. We used a simple model containing the essential elements of this functional system to investigate which musculoskeletal features are important for increasing the mechanical work done in a muscle-powered acceleration. The muscle model consisted of a muscle-like actuator with frog hindlimb muscle properties, operating across a lever to accelerate a load. We tested this model in configurations with and without a series elastic element and with and without a variable mechanical advantage. When total muscle shortening was held constant at 30%, the model produced the most work when the muscle operated with a series elastic element and an effective mechanical advantage that increased throughout the contraction (31 J kg-1 muscle vs26.6 J kg-1 muscle for the non-compliant, constant mechanical advantage configuration). We also compared the model output with the dynamics of jumping bullfrogs, measured by high-speed video analysis, and the length changes of the plantaris muscle, measured by sonomicrometry. This comparison revealed that the length, force and power trajectory of the body of jumping frogs could be accurately replicated by a model of a fully active muscle operating against an inertial load, but only if the model muscle included a series elastic element. Sonomicrometer measurements of the plantaris muscle revealed an unusual, biphasic pattern of shortening, with high muscle velocities early and late in the contraction, separated by a period of slow contraction. The model muscle produced this pattern of shortening only when an elastic element was included.

These results demonstrate that an elastic element can increase the work output in a muscle-powered acceleration. Elastic elements uncouple muscle fiber shortening velocity from body movement to allow the muscle fibers to operate at slower shortening velocities and higher force outputs. A variable muscle mechanical advantage improves the effectiveness of elastic energy storage and recovery by providing an inertial catch mechanism. These results can explain the high power outputs observed in jumping frogs. More generally,our model suggests how the function of non-muscular elements of the musculoskeletal system enhances performance in muscle-powered accelerations.
Regeneration of ultraviolet-sensitive cones in the retinal cone mosaic of thyroxin-challenged post-juvenile rainbow trout (Oncorhynchus mykiss)
Authors: Hawryshyn Craig W. , Martens Garnet , Allison W. Ted , Anholt Bradley R.
Published: June 2003

Previous studies in our laboratory have examined the loss of ultraviolet-sensitive (UVS) cones and UV sensitivity. This study looks at the question of regeneration of UVS cones and its topographic distribution, along with several other measures of the cone mosaic. Topography of the cone mosaic in rainbow trout smolts (post-metamorphic juveniles) was examined under normal growth conditions and during an exogenous thyroid hormone (TH) challenge. Growth of trout retina was studied over six weeks. Retinas sampled at 0, 3 and 6 weeks were embedded in EPON resin, and thick (1 μm) tangential sections were stained with Richardson's stain. Sites representing central ventral,ventral, temporal, dorsal and nasal retina were sampled. Variables measured were cone densities, mean double cone diameter and mean spacing between cones of the same type. These same variables were compared with those of fish that were challenged with l-thyroxin (T4), and regeneration of UVS cones was assessed. Principal components of the correlation matrix of all photoreceptor measurements were analysed using analysis of variance. Here, we show several interesting effects of thyroxin exposure on post-metamorphic rainbow trout: (1) controls at week 0 have a high density of UVS cones in the temporal and dorsal sampling regions and a high density of blue(short-wavelength)-sensitive (SWS) and double cones across all regions sampled; (2) both control and TH-treated fish had less abundant, larger and less tightly packed SWS and double cones and a lower density of UVS cones in the temporal and dorsal sampling regions three and six weeks into the experiment compared with the starting condition at week 0; (3) fish treated with TH had a higher UVS cone density in the nasal and ventral sampling regions and there were higher densities of SWS and double cones in the central ventral, temporal and ventral regions, but lower densities in the nasal sampling regions, relative to the controls. The regeneration of UVS cones into the ventral retinal hemisphere in post-juvenile salmonids has important implications for visually guided behavior.
Thermoregulation is the pits: use of thermal radiation for retreat site selection by rattlesnakes
Authors: Krochmal Aaron R. , Bakken George S.
Published: June 2003

Pitvipers (Viperidae: Crotalinae) possess unique sensory organs,the facial pits, capable of sensing subtle fluctuations in thermal radiation. Prey acquisition has long been regarded as the sole function of the facial pits. However, the ability to sense thermal radiation could also direct thermoregulatory behavior by remotely sensing nearby surface temperatures. Using a series of behavioral arenas of varying spatial complexity and ecological relevance, we surveyed the ability of the western diamondback rattlesnake Crotalus atrox to direct successful thermoregulatory movements with either functional or disabled facial pits. We found that western diamondback rattlesnakes could base thermoregulatory decisions on thermal radiation cues when their pits were functional, but not when blocked. Our results indicate that the facial pit is part of a generalized sense, and suggest thermoregulation as an alternative hypothesis to prey acquisition for the origin of facial pits.
Maturation of cardiovascular control mechanisms in the embryonic emu(Dromiceius novaehollandiae)
Authors: Crossley Dane A. , Bagatto Brian P. , Dzialowski Edward M. , Burggren Warren W.
Published: June 2003

Our understanding of avian embryonic cardiovascular regulation has been based on studies in chickens. The present study was undertaken to determine if the patterns established in chickens are generally applicable to the emu, a ratite bird species. We studied cardiovascular physiology over the interval from 60% to 90% of the emu's 50-day incubation period. During this period,embryonic emus exhibit a slight fall in resting heart rate (from 171 beats min-1 to 154 beats min-1) and a doubling of mean arterial pressure (from 1.2 kPa to 2.6 kPa). Exposures to 15% or 10%O2 initially decreased heart rate during the first period of emu incubation studied [60% of incubation (60%I)] but increased heart rate in the 90%I group. Arterial pressure responded to hypoxia with an initial depression(-1.6 kPa) at 60%I and 70%I but showed no response during the later periods of incubation (80%I and 90%I). In addition, tonic stimulation of both cholinergic and adrenergic (α and β) receptors was present on heart rate at 70%I, with the cholinergic and β-adrenergic tone increasing in strength by 90%I. Arterial pressure was dependent on a constant β-adrenergic and constant α-adrenergic tone from 60%I to 90%I. A comparison with embryonic white leghorn chickens over a similar window of incubation revealed that emus and white leghorn chickens both possess an adrenergic tone on heart rate and pressure but that only emus possess a cholinergic tone on heart rate. Collectively, these data indicate that the maturation of cardiovascular control systems differs between white leghorn chickens and emus, inviting investigation of additional avian species to determine other patterns.
Struktur‐Wirkungs‐Beziehungen von Oxazolidinonen: Grundlage der Entwicklung von Linezolid
Authors: Barbachyn Michael R. , Ford Charles W.
Published: May 2003

Die zunehmende Resistenz von Bakterien gegen Antibiotika ist gegenwärtig eines der drängendsten Probleme in der Medizin. In dieser Hinsicht besonders bedenklich sind durch mehrfachresistente Gram‐positive Pathogene verursachte Infektionen, die signifikante Krankheits‐ und Sterblichkeitsziffern verursachen. Eine Reihe von Lösungsansätzen wurde zur Bekämpfung der Bakterienresistenz eingeführt. Der am häufigsten angewendete Ansatz beruht auf der Modifizierung existierender Klassen von Antibiotika zur Herstellung neuer Analoga mit verbesserten Eigenschaften. Weitere Strategien sind die Kombination von antibakteriellen mit anderen Wirkstoffen und die Anwendung von Zusatztherapeutika wie Immunmodulatoren. Die größte Bedeutung hat aber zweifellos die Entwicklung neuer Klassen antibakterieller Wirkstoffe mit neuartigen Wirkmechanismen, die sich durch das Fehlen von Kreuzresistenzen mit existierenden antimikrobiellen Wirkstoffen auszeichnen. Dieser Aufsatz schildert die Arbeiten, die zur Entwicklung von Linezolid führten, dem ersten klinisch nutzbaren Oxazolidinon‐Antibiotikum.
Titelbild: Isolation and Structural Proof of the Large Diamond Molecule, Cyclohexamantane (C26H30) (Angew. Chem. 18/2003)
Authors: Dahl Jeremy E. P. , Moldowan J. Michael , Peakman Torren M. , Clardy Jon C. , Lobkovsky Emil , Olmstead Marilyn M. , May Paul W. , Davis Tim J. , Steeds John W. , Peters Ken E. , Pepper Andy , Ekuan Andy , Carlson Robert M. K.
Published: May 2003

Ein brillantes Beispiel dafür, welche Schätze Erdöl hervorbringen kann: Das Titelbild zeigt die Überlagerung der Kohlenstoffstruktur des kürzlich isolierten Cyclohexamantans, C26H30, mit einem Diamantgitter. Im äußeren Kreis sieht man Projektionen einzelner Cyclohexamantan‐Moleküle aus unterschiedlichen Perspektiven, unter anderem den (100)‐, (110)‐, (111)‐Ebenen des Diamants entsprechend. Mehr darüber finden Sie in der Zuschrift von J. E. P. Dahl et al. auf S. 2086 ff.
Oxazolidinone Structure–Activity Relationships Leading to Linezolid
Authors: Barbachyn Michael R. , Ford Charles W.
Published: May 2003

The development of bacterial resistance to currently available antibacterial agents is a growing global health problem. Of particular concern are infections caused by multidrug‐resistant Gram‐positive pathogens which are responsible for significant morbidity and mortality in both the hospital and community settings. A number of solutions to the problem of bacterial resistance are possible. The most common approach is to continue modifying existing classes of antibacterial agents to provide new analogues with improved attributes. Other successful strategies are to combine existing antibacterial agents with other drugs as well as the development of improved diagnostic procedures that may lead to rapid identification of the causative pathogen and permit the use of antibacterial agents with a narrow spectrum of activity. Finally, and most importantly, the discovery of novel classes of antibacterial agents employing new mechanisms of action has considerable promise. Such agents would exhibit a lack of cross‐resistance with existing antimicrobial drugs. This review describes the work leading to the discovery of linezolid, the first clinically useful oxazolidinone antibacterial agent.
Catalytic Synthesis of Ammonia—A “Never‐Ending Story”?
Authors: Schlögl Robert
Published: May 2003

Nitrogen atoms are essential for the function of biological molecules and thus are and important component of fertilizers and medicaments. Bonds to nitrogen also find nonbiological uses in dyes, explosives, and resins. The synthesis of all these materials requires ammonia as an activated nitrogen building block. This situation is true for natural processes and the chemical industry. Knowledge of the various techniques for the preparation of ammonia is thus of fundamental importance for chemistry. The Haber–Bosch synthesis was the first heterogeneous catalytic system employed in the chemical industry and is still in use today. Understanding the mechanism and the translation of the knowledge into technical perfection has become a fundamental criterion for scientific development in catalysis research.
Cover Picture: Isolation and Structural Proof of the Large Diamond Molecule, Cyclohexamantane (C26H30) (Angew. Chem. Int. Ed. 18/2003)
Authors: Dahl Jeremy E. P. , Moldowan J. Michael , Peakman Torren M. , Clardy Jon C. , Lobkovsky Emil , Olmstead Marilyn M. , May Paul W. , Davis Tim J. , Steeds John W. , Peters Ken E. , Pepper Andy , Ekuan Andy , Carlson Robert M. K.
Published: May 2003

A brilliant example of the treasures that can be found in petroleum: The cover picture shows the carbon framework structure of the newly identified diamond molecule cyclohexamantane, C26H30, superimposed on a diamond lattice surrounded by individual cyclohexamantane molecules shown from a variety of perspectives, such as their diamond (100), (110), (111) faces. More details are given in the Communication by J. E. P. Dahl et al. on page 2040 ff.
Functional and prognostic relevance of the −173 polymorphism of the macrophage migration inhibitory factor gene in systemic‐onset juvenile idiopathic arthritis
Authors: De Benedetti Fabrizio , Meazza Cristina , Vivarelli Marina , Rossi Federica , Pistorio Angela , Lamb Rebecca , Lunt Mark , Thomson Wendy ,   the British Paediatric Rheumatology Study Group, Ravelli Angelo , Donn Rachelle , Martini Alberto
Published: May 2003

Objective

To address the functional and prognostic relevance of the −173 single‐nucleotide G‐to‐C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic‐onset juvenile idiopathic arthritis (systemic‐onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease.

Methods

A total of 136 patients with systemic‐onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF‐173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme‐linked immunosorbent assay. The evaluation of the association of the MIF‐173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C‐HAQ); and 3) data concerning the treatment regimens during the disease course.

Results

Systemic‐onset JIA patients carrying a MIF‐173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF‐173*C allele than in MIF‐173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF‐173*C allele. At the last visit, the numbers of joints with active arthritis, the C‐HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF‐173*C allele.

Conclusion

Our study shows the functional relevance of the MIF‐173 polymorphism and suggests that the MIF‐173*C allele is a predictor of poor outcome in systemic‐onset JIA.