bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitating undergraduate interprofessional learning in healthcare: comparing classroom and clinical learning for nursing and medical students
Authors: Morison Sue , Boohan Mairead , Jenkins John , Moutray Marianne 
Published: May 2003

AbstractThere has been increasing emphasis on the important role that interprofessional education (IPE) must play in educating and developing present and future healthcare professionals. However, clarity is urgently needed regarding appropriate strategies for its timing, content, delivery and assessment. This study focuses on the development of an undergraduate IPE programme for medical and nursing students. It compares learning opportunities in classroom and clinical areas and identifies suitable pedagogical strategies and subject areas. The programme consisted of 2 weeks of classroom‐based learning for all 130 participating students, followed by 6 weeks on shared placement for 35 of the 113 medical and all 17 nursing students. A triangulation of data‐collection methods was used to help strengthen reliability and validity and provide a more comprehensive analysis. In both classroom and clinical areas, successful methods of delivery for IPE were those that enabled exchanges of perspectives. Ward‐based IPE was regarded as particularly effective in encouraging students to begin to feel part of a clinical team. In contrast, classroom‐based learning enabled them to know about teamwork, but not to experience it. Practical issues of shift and timetable incompatibility were the most significant barriers to successful placement‐shared learning. Developments in this area will need to focus on those elements of clinical practice which bring students together for collaborative involvement in activities that maximize the benefits resulting from the investment of time and effort involved. We conclude that undergraduate IPE opportunities have an important role to play in enabling students to learn about the roles and responsibilities of others and the impact of this on their own practice. It should be the first step towards developing practitioners who, whilst retaining their own unique professional identity, are able to understand and respect the roles of other healthcare professionals and work collaboratively to improve patient care.
Do Perceived Attitudes of Physicians and Hospital Staff Affect Breastfeeding Decisions?
Authors: DiGirolamo Ann M. , Grummer‐Strawn Laurence M. , Fein Sara B. 
Published: May 2003

ABSTRACT:  Background: In the United States, since a substantial percentage of mothers are not breastfeeding, research is needed to assess important influences on breastfeeding. The current study assessed the impact on breastfeeding of the perceived attitudes of health care providers about infant feeding.Methods: A longitudinal mail survey (1993–1994) was administered to 1620 women prenatally through 12 months postpartum; the current study focused on the prenatal and neonatal periods (66% response rate). The outcome variable was failure to breastfeed beyond 6 weeks. Predictor variables were the mother's perceptions of her prenatal physician's and hospital staff's attitudes on infant feeding. Analysis controlled for mother's prenatal breastfeeding intentions, father's feeding preference, and demographic and psychosocial variables.Results: Forty‐one percent of the mothers were not breastfeeding at 6 weeks postpartum. Substantial percentages of mothers reported that physicians and hospital staff expressed a preference for breastfeeding (38% and 57%, respectively), or expressed no preference (61% and 42%, respectively), whereas few favored formula feeding. Adjusted analyses indicated that “no preference” by hospital staff was a significant risk factor for failure to breastfeed beyond 6 weeks. “No preference” by physicians did not significantly influence breastfeeding outcome in these analyses. Further analyses indicated that the effects of perceived hospital staff attitudes were only present for mothers who intended prenatally to breastfeed for 2 months or less.Conclusions: Many women did not report receiving positive breastfeeding messages from their health caregivers and hospital staff. A perceived neutral attitude from the hospital staff is related to not breastfeeding beyond 6 weeks, especially among mothers who prenatally intended to breastfeed for only a short time. (BIRTH 30:2 June 2003)
A Simplified Predictive Index for the Detection of Women at Risk for Postnatal Depression
Authors: Webster Joan , Pritchard Margo A. , Creedy Debra , East Chris 
Published: May 2003

Background: Many women who suffer from postnatal depression are never diagnosed or treated. The objective of this study was to develop an index for use in maternity settings that identifies women who may be at risk for postnatal depression.Methods: Women (n = 1762) attending the ‘‘booking‐in’’ clinic were screened for antenatal risk factors for postnatal depression. On the third postnatal day eligible women were screened for postnatal risk factors. The Edinburgh Postnatal Depression Scale was mailed to participants16 weeks after the birth. A predictive index was developed, based on the mean Edinburgh Postnatal Depression Scale scores for each risk factor. The sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the diagnostic value of the index.Results: Seven hundred and twenty‐three (50.1%) of the eligible women completed all phases of the study. Of this group, 93 (12.2%) women scored higher than 12 on the Edinburgh Postnatal Depression Scale. At a cutoff of 6, the index had positive predictive value of 39.8 percent for postnatal depression, a threefold improvement over the base rate.Conclusion: The Brisbane Postnatal Depression Index provides a clinically useful method for identifying women at risk for developing postnatal depression. It has applications for early intervention or to identify high‐risk groups for research purposes. (BIRTH 30:2 June 2003)
Structural Basis for Distinctions between Substrate and Inhibitor Specificities for Feline Immunodeficiency Virus and Human Immunodeficiency Virus Proteases
Authors: Lin Ying-Chuan , Beck Zachary , Morris Garrett M. , Olson Arthur J. , Elder John H. 
Published: May 2003

ABSTRACTWe used feline immunodeficiency virus (FIV) protease (PR) as a mutational framework to define determinants for the observed substrate and inhibitor specificity distinctions between FIV and human immunodeficiency virus (HIV) PRs. Multiple-substitution mutants were constructed by replacing the residues in and around the active site of FIV PR with the structurally equivalent residues of HIV-1 PR. Mutants included combinations of three critical regions (FIV numbering, with equivalent HIV numbering in superscript): I3732V in the active core region; N5546M, M5647I, and V5950I in the flap region; and L9780T, I9881P, Q9982V, P10083N, and L10184I in the 90s loop region. Significant alterations in specificity were observed, consistent with the involvement of these residues in determining the substrate-inhibitor specificity distinctions between FIV and HIV PRs. Two previously identified residues, I35 and I57 of FIV PR, were intolerant to substitution and yielded inactive PRs. Therefore, we attempted to recover the activity by introducing secondary mutations. The addition of G6253F and K6354I, located at the top of the flap and outside the active site, compensated for the activity lost in the I5748G substitution mutants. An additional two substitutions, D10588N and N8874T, facilitated recovery of activity in mutants that included the I3530D substitution. Determination ofKivalues of potent HIV-1 PR inhibitors against these mutants showed that inhibitor specificity paralleled that of HIV-1 PR. The findings indicate that maintenance of both substrate and inhibitor specificity is a function of interactions between residues both inside and outside the active site. Thus, mutations apparently peripheral to the active site can have a dramatic influence on inhibitor efficacy.
Genome Replication, Virion Secretion, and e Antigen Expression of Naturally Occurring Hepatitis B Virus Core Promoter Mutants
Authors: Parekh Sameer , Zoulim Fabien , Ahn Sang Hoon , Tsai Adrienne , Li Jisu , Kawai Shigenobu , Khan Nasser , Trépo Christian , Wands Jack , Tong Shuping 
Published: May 2003

ABSTRACT

The core promoter mutants of hepatitis B virus (HBV) emerge as the dominant viral population at the late HBeAg and the anti-HBe stages of HBV infection, with the A1762T/G1764A substitutions as the hotspot mutations. The double core promoter mutations were found by many investigators to moderately enhance viral genome replication and reduce hepatitis B e antigen (HBeAg) expression. A much higher replication capacity was reported for a naturally occurring core promoter mutant implicated in the outbreak of fulminant hepatitis, which was caused by the neighboring C1766T/T1768A mutations instead. To systemically study the biological properties of naturally occurring core promoter mutants, we amplified full-length HBV genomes by PCR from sera of HBeAg
+
individuals infected with genotype A. All 12 HBV genomes derived from highly viremic sera (5 × 10
9
to 5.7 × 10
9
copies of viral genome/ml) harbored wild-type core promoter sequence, whereas 37 of 43 clones from low-viremia samples (0.2 × 10
7
to 4.6 × 10
7
copies/ml) were core promoter mutants. Of the 11 wild-type genomes and 14 core promoter mutants analyzed by transfection experiments in human hepatoma cell lines, 6 core promoter mutants but none of the wild-type genomes replicated at high levels. All had 1762/1764 mutations and an additional substitution at position 1753 (T to C), at position 1766 (C to T), or both. Moreover, these HBV clones varied greatly in their ability to secrete enveloped viral particles irrespective of the presence of core promoter mutations. High-replication clones with 1762/1764/1766 or 1753/1762/1764/1766 mutations expressed very low levels of HBeAg, whereas high-replication clones with 1753/1762/1764 triple mutations expressed high levels of HBeAg. Experiments with site-directed mutants revealed that both 1762/1764/1766 and 1753/1762/1764/1766 mutations conferred significantly higher viral replication and lower HBeAg expression than 1762/1764 mutations alone, whereas the 1753/1762/1764 triple mutant displayed only mild reduction in HBeAg expression similar to the 1762/1764 mutant. Thus, core promoter mutations other than those at positions 1762 and 1764 can have major impact on viral DNA replication and HBeAg expression.
Complete Sequence and Genomic Analysis of Rhesus Cytomegalovirus
Authors: Hansen Scott G. , Strelow Lisa I. , Franchi David C. , Anders David G. , Wong Scott W. 
Published: May 2003

ABSTRACT
The complete DNA sequence of rhesus cytomegalovirus (RhCMV) strain 68-1 was determined with the whole-genome shotgun approach on virion DNA. The RhCMV genome is 221,459 bp in length and possesses a 49% G+C base composition. The genome contains 230 potential open reading frames (ORFs) of 100 or more codons that are arranged colinearly with counterparts of previously sequenced betaherpesviruses such as human cytomegalovirus (HCMV). Of the 230 RhCMV ORFs, 138 (60%) are homologous to known HCMV proteins. The conserved ORFs include the structural, replicative, and transcriptional regulatory proteins, immune evasion elements, G protein-coupled receptors, and immunoglobulin homologues. Interestingly, the RhCMV genome also contains sequences with homology to cyclooxygenase-2, an enzyme associated with inflammatory processes. Closer examination identified a series of candidate exons with the capacity to encode a full-length cyclooxygenase-2 protein. Counterparts of cyclooxygenase-2 have not been found in other sequenced herpesviruses. The availability of the complete RhCMV sequence along with the ability to grow RhCMV in vitro will facilitate the construction of recombinant viral strains for identifying viral determinants of CMV pathogenicity in the experimentally infected rhesus macaque and to the development of CMV as a vaccine vector.
Cytolysis by CCR5-Using Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Is Dependent on Membrane Fusion and Can Be Inhibited by High Levels of CD4 Expression
Authors: LaBonte Jason A. , Madani Navid , Sodroski Joseph 
Published: May 2003

ABSTRACTT-tropic (X4) and dualtropic (R5X4) human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins kill primary and immortalized CD4+CXCR4+T cells by mechanisms involving membrane fusion. However, because much of HIV-1 infection in vivo is mediated by M-tropic (R5) viruses whose envelope glycoproteins use CCR5 as a coreceptor, we tested a panel of R5 and R5X4 envelope glycoproteins for their ability to lyse CCR5+target cells. As is the case for CXCR4+target cells, HIV-1 envelope glycoproteins expressed by single-round HIV-1 vectors killed transduced CD4+CCR5+cells in a membrane fusion-dependent manner. Furthermore, a CD4-independent R5 HIV-1 envelope glycoprotein was able to kill CD4-negative target cells expressing CCR5, demonstrating that CD4 is not intrinsically required for the induction of death. Interestingly, high levels of CD4 expression protected cells from lysis and syncytium formation mediated by the HIV-1 envelope glycoproteins. Immunoprecipitation experiments showed that high levels of CD4 coexpression inhibited proteolytic processing of the HIV-1 envelope glycoprotein precursor gp160. This inhibition could be overcome by decreasing the CD4 binding ability of gp120. Studies were also undertaken to investigate the ability of virion-bound HIV-1 envelope glycoproteins to kill primary CD4+T cells. However, neither X4 nor R5X4 envelope glycoproteins on noninfectious virions caused death in primary CD4+T cells. These results demonstrate that the interaction of CCR5 with R5 HIV-1 envelope glycoproteins capable of inducing membrane fusion leads to cell lysis; overexpression of CD4 can inhibit cell killing by limiting envelope glycoprotein processing.
Varicella-Zoster Virus Gene 66 Transcription and Translation in Latently Infected Human Ganglia
Authors: Cohrs Randall J. , Gilden Donald H. , Kinchington Paul R. , Grinfeld Esther , Kennedy Peter G. E. 
Published: May 2003

ABSTRACT
Latent infection with varicella-zoster virus (VZV) is characterized by restricted virus gene expression and the absence of virus production. Of the ∼70 predicted VZV genes, only five (genes 4, 21, 29, 62, and 63) have been shown by multiple techniques to be transcribed during latency. IE62, the protein product of VZV gene 62, is the major immediate-early (IE) virus-encoded transactivator of viral gene transcription and plays a pivotal role in transactivating viral genes during lytic infection. The protein kinase (66-pk) encoded by VZV gene 66 phosphorylates IE62, resulting in cytoplasmic accumulation of IE62 that mitigates nuclear IE62-induced gene activation. Analysis of latently infected human trigeminal ganglia for 66-pk expression by reverse transcriptase-dependent nested PCR, including DNA sequence analysis, in situ hybridization, and immunohistochemistry, revealed VZV open reading frame 66 to be a previously unrecognized latently expressed virus gene and suggests that prevention of IE62 import to the nucleus by VZV 66-pk phosphorylation is one possible mechanism by which VZV latency is maintained.
Replicating Parvoviruses That Target Colon Cancer Cells
Authors: Malerba M. , Daeffler L. , Rommelaere J. , Iggo R. D. 
Published: May 2003

ABSTRACT
The wnt signaling pathway is constitutively activated in colon tumors by mutations in the adenomatous polyposis coli and β-catenin genes. We have modified the minute virus of mice (MVM) P4 promoter to make it responsive to wnt signaling by inserting binding sites for the heterodimeric β-catenin/Tcf transcription factor. In luciferase assays we can see up to 20-fold selectivity of Tcf mutant P4 promoters for cells with activated wnt signaling. Hybrid MVM/H-1 viruses containing Tcf mutant promoters were tested for NS1 expression, viral DNA replication, virus replication, and cytopathic effect on colon, lung, kidney, and cervical cancer cell lines. Activation of the wnt pathway by expression of ΔN-β-catenin increased NS1 expression and viral burst size in 293T and H1299 lung cancer cells, showing that the Tcf mutant P4 promoter can respond to wnt signals in the context of the virus. Compared to the parental virus, the burst size of the Tcf mutant viruses was reduced at least 1,000-fold in H1299, 293T, NB324K, and HeLa cells, which have inactive wnt signaling pathways. The burst size and cytopathic effect of the Tcf viruses was near wild-type levels in SW480 and Isreco1 colon cancer cell lines, which have high Tcf activity. The high specificity of these viruses should permit the development of H-1 virus-based vectors which combine high safety and greater efficacy in cancer therapy.
Monocytes Treated with Human Immunodeficiency Virus Tat Kill Uninfected CD4+Cells by a Tumor Necrosis Factor-Related Apoptosis-Induced Ligand-Mediated Mechanism
Authors: Yang Yida , Tikhonov Ilia , Ruckwardt Tracy J. , Djavani Mahmoud , Zapata Juan Carlos , Pauza C. David , Salvato Maria S. 
Published: May 2003

ABSTRACTThe human immunodeficiency virus (HIV) Tat protein has a critical role in viral transcription, but this study focuses on its additional role as an extracellular effector of lymphocyte cell death. It is well known that Tat induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in peripheral blood mononuclear cells (PBMC), and we show that the majority of TRAIL is produced by the monocyte subset of PBMC. Human monocytes and U937 monoblastoid cells did not take up soluble HIV Tat-86, as T cells did, yet produced more TRAIL than did T cells. TRAIL secretion was induced by Tat and by a cysteine-rich peptide of Tat but not by sulfhydryl-modified Tat toxoid. Although there was only a slight increase in cell surface expression of TRAIL on monocytes, sufficient TRAIL was secreted to be toxic for T cells. The cytotoxicity of Tat-stimulated monocyte medium could be blocked by a TRAIL-neutralizing antibody. T cells treated with Tat did not secrete enough TRAIL to mediate cell death in our assay. Remarkably, uninfected T cells are more susceptible to TRAIL than are HIV-infected T cells. The production of TRAIL by Tat-stimulated monocytes provides a mechanism by which HIV infection can destroy uninfected bystander cells.
Stem-Loop III in the 5′ Untranslated Region Is a
cis
-Acting Element in Bovine Coronavirus Defective Interfering RNA Replication
Authors: Raman Sharmila , Bouma Peter , Williams Gwyn D. , Brian David A. 
Published: May 2003

ABSTRACT

Higher-order structures in the 5′ untranslated region (UTR) of plus-strand RNA viruses are known in many cases to function as
cis
-acting elements in RNA translation, replication, or transcription. Here we describe evidence supporting the structure and a
cis
-acting function in defective interfering (DI) RNA replication of stem-loop III, the third of four predicted higher-order structures mapping within the 210-nucleotide (nt) 5′ UTR of the 32-kb bovine coronavirus (BCoV) genome. Stem-loop III maps at nt 97 through 116, has a calculated free energy of −9.1 kcal/mol in the positive strand and −3.0 kcal/mol in the negative strand, and has associated with it beginning at nt 100 an open reading frame (ORF) potentially encoding an 8-amino-acid peptide. Stem-loop III is presumed to function in the positive strand, but its strand of action has not been established. Stem-loop III (i) shows phylogenetic conservation among group 2 coronaviruses and appears to have a homolog in coronavirus groups 1 and 3, (ii) has in all coronaviruses for which sequence is known a closely associated short, AUG-initiated intra-5′ UTR ORF, (iii) is supported by enzyme structure-probing evidence in BCoV RNA, (iv) must maintain stem integrity for DI RNA replication in BCoV DI RNA, and (v) shows a positive correlation between maintenance of the short ORF and maximal DI RNA accumulation in BCoV DI RNA. These results indicate that stem-loop III in the BCoV 5′ UTR is a
cis
-acting element for DI RNA replication and that its associated intra-5′ UTR ORF may function to enhance replication. It is postulated that these two elements function similarly in the virus genome.
Structure-Function Analysis of Herpes Simplex Virus Type 1 gD and gH-gL: Clues from gDgH Chimeras
Authors: Cairns Tina M. , Milne Richard S. B. , Ponce-de-Leon Manuel , Tobin Deanna K. , Cohen Gary H. , Eisenberg Roselyn J. 
Published: May 2003

ABSTRACT
In alphaherpesviruses, glycoprotein B (gB), gD, gH, and gL are essential for virus entry. A replication-competent gL-null pseudorabies virus (PrV) (B. G. Klupp and T. C. Mettenleiter, J. Virol. 73:3014-3022, 1999) was shown to express a gDgH hybrid protein that could replace gD, gH, and gL in cell-cell fusion and null virus complementation assays. To study this phenomenon in herpes simplex virus type 1 (HSV-1), we constructed four gDgH chimeras, joining the first 308 gD amino acids to various gH N-terminal truncations. The chimeras were named for the first amino acid of gH at which each was truncated: 22, 259, 388, and 432. All chimeras were immunoprecipitated with both gD and gH antibodies to conformational epitopes. Normally, transport of gH to the cell surface requires gH-gL complex formation. Chimera 22 contains full-length gH fused to gD308. Unlike PrV gDgH, chimera 22 required gL for transport to the surface of transfected Vero cells. Interestingly, although chimera 259 failed to reach the cell surface, chimeras 388 and 432 exhibited gL-independent transport. To examine gD and gH domain function, each chimera was tested in cell-cell fusion and null virus complementation assays. Unlike PrV gDgH, none of the HSV-1 chimeras substituted for gL for fusion. Only chimera 22 was able to replace gH for fusion and could also replace either gH or gD in the complementation assay. Surprisingly, this chimera performed very poorly as a substitute for gD in the fusion assay despite its ability to complement gD-null virus and bind HSV entry receptors (HveA and nectin-1). Chimeras 388 and 432, which contain the same portion of gD as that in chimera 22, substituted for gD for fusion at 25 to 50% of wild-type levels. However, these chimeras functioned poorly in gD-null virus complementation assays. The results highlight the fact that these two functional assays are measuring two related but distinct processes.