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PubMed2005

Involving women with breast cancer in the development of a patient information leaflet for anticipatory nausea and vomiting.

As chemotherapy regimens increase in toxicity and changes in service provision move towards a more ambulatory outpatient basis, patients are often coping with side effects of treatment in isolation. Despite advances in pharmacological control, for some patients nausea and vomiting can be problematic. For some this can develop into anticipatory nausea and vomiting (ANV), which can severely effect the patients physical and psychological well-being. It is well recognised that the giving of realistic and understandable information is paramount to empower patients in their individual coping. A plethora of literature supports the use of Patient Information Leaflets as a means to educate and empower patients within their treatment trajectory. This paper discusses the authors' experiences in developing a Patient Information Leaflet, designed to assist breast cancer patients in understanding and coping with the symptoms of ANV. The patient's needs were sought to add clarity to the development and design of the leaflet. The authors conclude that developing a Patient Information Leaflet was a major undertaking in terms of time and resources.

Breast Neoplasms↗
PubMed2024

Dynamics of antibiotic resistance genes during manure composting: Reduction in herbivores manure and accumulation in carnivores.

The elevated levels of antibiotic resistance genes (ARGs) in livestock manure represent a significant threat to both the environment and human health. Composting has been recognized as an effective strategy to mitigate the abundance of ARGs in manure. However, notable rebounds in ARGs abundance have been observed during this process. This study explored the changes in ARGs abundance and the underlying influencing factors during the composting of carnivore (chicken and pig) and herbivore (sheep and cow) manures, along with mushroom residues. The findings revealed that the total relative abundance of ARGs increased by 6.96 and 10.94 folds in chicken and pig manure composts, respectively, whereas it decreased by a remarkable 91.72% and 98.37% in sheep and cow manure composts. Nitrogen content emerged as the primary physicochemical factors governing the abundance of ARGs in chicken and pig manure composts. Conversely, carbon content played a pivotal role in determining ARGs abundance in chicken and pig manure composts. Furthermore, the presence of dominant hosts, such as Corynebacterium, Bacillus, and Clostridium, along with emerging bacteria like Thermobifida, Saccharomonospora, and Actinomadura, contributed significantly to the enrichment of total ARGs, including tetG, tetO, tetX, and sul2, in chicken and pig manure composts. The coexistence of these genes with mobile genetic elements and a plethora of host bacteria, coupled with their high abundance, renders them particularly high-risk ARGs. On the other hand, the observed decrease in the abundance of total ARGs in sheep and cow manure composts can be attributed to the decline in the population of host bacteria, specifically Atopostipes, Psychrobacter, and Corynebacterium. Collectively, these results provide crucial insights into the management of ARGs risks and offer essential theoretical support for enhancing the safe utilization of organic fertilizer in agriculture.

Manure↗
PubMed2006

Quaternary benzo[c]phenathridine alkaloids sanguinarine and chelerythrine do not affect transcriptional activity of aryl hydrocarbon receptor: analyses in rat hepatoma cell line H4IIE.luc.

Quaternary benzo[c]phenanthridine alkaloids (QBAs) sanguinarine and chelerythrine exert a plethora of biological activities. Nevertheless, the specific cellular target for these alkaloids within the cell was not identified as far. Several literary data indicate that biological effects of QBAs could be associated with aryl hydrocarbon receptor (AhR) signaling pathway, including cytochrome P450 CYP1A, however, available information are controversial. In this work we analyzed the effects of sanguinarine and chelerythrine on AhR activity in rat hepatoma cells HII4E.luc stably transfected with dioxin responsive element fused to luciferase gene (DRE-LUC). Studied QBAs were tested in submicromolar concentration range (0.0001-1 microM) and in incubation times 6, 24 and 48 h. Transcriptional activity of AhR was monitored by chemiluminiscence measurement of luciferase catalytic activity. Sanguinarine and chelerythrine did not activated AhR in any time or dose tested. Chelerythrine (1 microM) but not sanguinarine caused moderate inhibition of AhR activation by 10 picomolar dioxin (exponential phase of receptor activation). In contrast, AhR activation by 2.5 nM dioxin (saturated receptor) was not affected by either alkaloid tested. In conclusion, the findings presented here favor rather for inactivity or modest inhibitory effect of QBAs on AhR signaling pathways in vitro than for the activation of the receptor. Regarding the concentrations of QBAs occurring in vivo, the use of products containing sanguinarine and/or chelerythrine has low toxicological potential in terms of the interactions with AhR signaling pathways.

Alkaloids↗
PubMed2004

Yeast activator proteins and stress response: an overview.

Yeast, and especially Saccharomyces cerevisiae, are continuously exposed to rapid and drastic changes in their external milieu. Therefore, cells must maintain their homeostasis, which is achieved through a highly coordinated gene expression involving a plethora of transcription factors, each of them performing specific functions. Here, we discuss recent advances in our understanding of the function of the yeast activator protein family of eight basic-leucine zipper trans-activators that have been implicated in various forms of stress response.

Amino Acid Sequence↗
PubMed2005

Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells.

Extracellular HSP70 has been found to participate in both innate and adaptive immune responses. However, little is known about the molecular mechanisms that mediate this process. Previous reports suggest that HSP70 interacts with antigen presenting cells (APC) through a plethora of surface receptors. In this study, we have examined the relative binding of potential HSP70 receptors and found high affinity binding to LOX-1 but not other structures with a role in HSP70-APC interactions such as LRP/CD91, CD40, TLR2, TLR4 or another c-type lectin family member (DC-SIGN) closely related to LOX-1. In addition to APC, HSP70 can avidly bind to non-APC cell lines, especially those from epithelial or endothelial background.

Animals↗
PubMed2004

Protein secretion in Legionella pneumophila and its relation to virulence.

Protein secretion is a universal process of fundamental importance for various aspects of cell physiology including the infection of a host organism by a bacterial pathogen. Many Gram-negative pathogens export virulence-associated proteins across one or two cell membranes to their place of action using a wide plethora of secretory pathways with the objective of infecting the host. For Legionella pneumophila, a facultative intracellular, human pathogen which is ubiquitously found in natural and artificial aquatic environments, two major secretory pathways known to be involved in virulence have been described. These are the PilD-dependent Lsp type II secretion pathway and the type IV secretion system encoded by the dot/icm genes. In addition, a second type IV system, with high sequence similarity to the Agrobacterium tumefaciens VirB system for conjugal transfer of oncogenic DNA, is present. Albeit dispensable for intracellular growth, this type IV system is important for efficient host cell infection at lower temperatures. Further more, evidence exists for the presence of at least one type I secretion system in L. pneumophila as well as for the presence of a twin arginine dependent translocation (Tat) pathway. This is a recently detected, signal peptide-dependent, secretion pathway complementary to the well-known Sec-dependent pathway for protein transport across the cytoplasmic membrane.

Bacterial Proteins↗
PubMed2004

Expression of stress response genes in wine strains with different fermentative behavior.

The response to adverse growth conditions in yeast depends on the activation of signal transduction pathways which result in transcriptional changes and synthesis of protective molecules. During wine production, yeast cells are affected by a plethora of stress situations. In this work we have analyzed the fermentative behavior in synthetic must for six different wine yeast strains. In addition, we followed the expression of several stress response genes during the first half of the vinification. Our results indicate that common patterns of stress response are found among all the strains, but also that a subset of genes are differentially expressed according to the fermentative behavior of the various strains. Particularly, in the strains with the most severe fermentative problems, higher (and in some cases maintained) mRNA levels of many genes were found. The relevance of an equilibrium between stress response and growth efficiency during wine fermentation is discussed.

Carbohydrate Metabolism↗
PubMed2004

A novel method for displaying gait and clinical movement analysis data.

Plotting kinematic and kinetic data of a patient's movement patterns relative to normative values (i.e., mean and +/-1 S.D.) is a common method used by clinicians to visually assess deviations and interpret the patient's gait analysis data. This method of data interpretation is often time consuming and complex, especially when the process requires the inspection of a plethora of line graphs for numerous variables that are displayed across several report pages. In this paper we propose an alternate method for displaying movement pattern deviations relative to normative data by color-coding the magnitude and the direction of the deviation. An advantage of this approach is that a single page summary of all the deviation magnitudes can be displayed simultaneously, in a manner that is concise, visually effective and reduces complexity. The purpose of this paper is to describe the algorithmic development of the color-coding method.

Algorithms↗
PubMed2005

Flower development and evolution: gene duplication, diversification and redeployment.

Gene duplication and diversification can provide the raw material for the evolution of new morphologies. In plants, the numbers of MADS-box genes have multiplied considerably, resulting in a plethora of these transcriptional regulators in the angiosperms (flowering plants). MADS-box genes have been implicated in the regulation of a variety of flower developmental processes; therefore, understanding the functional consequences of duplication and diversification in this gene family can shed light on the evolution of different floral forms. Recent functional analyses of MADS-box gene lineages have demonstrated that in various instances these genes have swapped roles, acquired novel roles, or retained ancestral roles. These studies underscore the idea that gene function cannot be extrapolated from structural orthology.

Evolution, Molecular↗
PubMed2005

MicroRNAs as oncogenes.

MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Originally discovered in Caenorhabditis elegans, this group of tiny RNAs has moved to the forefront of biology. With over 300 miRNA genes identified in the human genome, and a plethora of predicted mRNA targets, it is believed that these small RNAs have a central role in diverse cellular and developmental processes. Concordant with this, aberrant expression of miRNA genes could lead to human disease, including cancer. Although the connection of miRNAs with cancer has been suspected for several years, four recent studies have confirmed the suspicion that miRNAs regulate cell proliferation and apoptosis, and play a role in cancer.

Animals↗
PubMed2006

Development and evolution of the migratory neural crest: a gene regulatory perspective.

The neural crest, a uniquely vertebrate characteristic, gives rise to pigment cells, much of the peripheral nervous system, the craniofacial skeleton, and a plethora of other cell types. Classical embryological studies have revealed important details about the migratory pathways followed by these cells, and their subsequent differentiation into diverse derivatives. More recently, many aspects of the molecular cascade of events involved in neural crest induction and generation of these migratory cells have been revealed. Formation of the neural crest appears to involve a network of interactions whereby signaling molecules initiate the induction and, subsequently, the establishment of the neural plate border, which is marked by expression of a characteristic set of transcription factors designated as neural plate border-specifiers. These in turn regulate other transcription factors termed neural crest-specifiers, which control genes involved in neural crest delamination, the generation of migratory cells and ultimately the acquisition of appropriate fates.

Animals↗
PubMed2004

RJLs: a new family of Ras-related GTP-binding proteins.

The Ras superfamily of GTP binding proteins encompasses several gene families that regulate a plethora of events in the eukaryotic cell. Here we describe a novel branch of this superfamily which we have named RJLs. These are present in many unicellular organisms and also in deuterostomes but apparently missing in some intermediary phyla, suggesting an intriguing possibility of lateral gene transference between lower and higher eukaryotes. RJLs lack classical membrane targeting signals and the conserved glutamine residue that coordinates GTP hydrolysis in other proteins from the Ras superfamily. Interestingly, chordate orthologues are chimeras fused to "J" domains in their C-terminal, suggesting that these proteins recruit Hsc70 to specific sites in the cell. Expression analysis of RJLs from chordates suggests predominant expression in nervous tissues, possibly reflecting a role for RJLs in the development or maintenance of the sophisticated chordate nervous system.

Amino Acid Sequence↗
PubMedDate not supplied

Belief in an afterlife, spiritual well-being and end-of-life despair in patients with advanced cancer.

Despite the plethora of research linking spirituality, religiosity and psychological well-being among people living with medical illnesses, the role of afterlife beliefs on psychological functioning has been virtually ignored. The present investigation assessed afterlife beliefs, spiritual well-being and psychological functioning at the end of life among 276 terminally ill cancer patients. Results indicated that belief in an afterlife was associated with lower levels of end-of-life despair (desire for death, hopelessness and suicidal ideation) but was not associated with levels of depression or anxiety. Further analyses indicated that when spirituality levels were controlled for, the effect of afterlife beliefs disappeared. The authors concluded that spirituality has a much more powerful effect on psychological functioning than beliefs held about an afterlife. Treatment implications are discussed.

Adaptation, Psychological↗
PubMed2025

Distinct rates of VUS reclassification are observed when subclassifying VUS by evidence level.

PURPOSE: Genetic testing commonly yields a plethora of variants of uncertain significance (VUS) that can lead to ongoing uncertainty for patients and their caregivers. Although all VUS hold uncertainty, some VUS have more evidence in support of pathogenicity, whereas others have more evidence of a benign role. Sharing these nuances can help guide the investment in follow-up clinical and research investigations and may, at times, influence medical decision making despite appreciated uncertainty. METHODS: Four clinical laboratories have been subclassifying VUS to help prioritize investigation and guide reporting decisions. Each laboratory developed a distinct approach for how these subclasses are used in their laboratories and, in some cases, displayed on reports. We examined the composition of each laboratory's VUS subclasses and the likelihood variants from each subclass were reclassified toward pathogenic or benign. RESULTS: We found that variants in the lowest subclass of VUS were never reclassified as likely pathogenic or pathogenic, whereas those in the highest subclass were much more likely to be reclassified as pathogenic or likely pathogenic. CONCLUSION: Given that forthcoming professional guidance in variant classification will advise the use of VUS subclasses, the experience of our laboratories in using VUS subclasses can inform future practices.

Humans↗
PubMed2004

GLUT1 endothelial reactivity distinguishes hepatic infantile hemangioma from congenital hepatic vascular malformation with associated capillary proliferation.

Hepatic vascular lesions in pediatric patients have overlapping definitions and a plethora of confusing terminology. The so-called hepatic infantile hemangioendothelioma (IHE) frequently coexists and shares some biological features with cutaneous juvenile hemangioma (CJH). To clarify the nature of hepatic vascular lesions in pediatric patients and to investigate the association between IHE and CJH, we reviewed the clinical features, imaging findings and histopathology of 19 cases of hepatic vascular lesions diagnosed at our institution over the last 33 years. Immunohistochemical stains for a battery of endothelial markers, including GLUT1, were performed. Our results indicate that there are two fundamentally different hepatic vascular lesions in infants and young children: GLUT1-positive hepatic infantile hemangioma (HIH) and GLUT1-negative hepatic vascular malformation with capillary proliferation (HVMCP). The finding of consistent GLUT1 immunoreactivity of endothelial cells in HIH not only offers a powerful tool to distinguish HIH from HVMCP, but also provides immunophenotypic evidence of the similar biological origins of CJH and HIH.

Arteriovenous Malformations↗
PubMed2005

PKC isoforms were reduced by lead in the developing rat brain.

A plethora of protein kinase C (PKC) isoforms play important roles in regulating synaptic plasticity and neurotransmitter release. Even though, most PKC isoforms are involved in Pb-induced neuronal toxicity, its mechanism is still unclear. The current study addresses the effect of Pb on PKC isoforms in different regions of the developing rat brain. Sprague-Dawley (SD) pregnant rats were exposed to 0.1% Pb as lead acetate dissolved in distilled deionized water (DDW) from gestation day 6 through 21 postnatal day (PND). Control rats were allowed to drink DDW. Pups were sacrificed on PND 1, 5, 10 and 45. Rat brain was immediately excised and separated into the brain stem (BS), the cerebellum (CB), the hippocampus (HC) and the frontal cortex (FC). The Pb level in different regions of the brain was determined using an analytical graphite tube atomizer (Varian). Typical PKC (alpha, beta, gamma), novel PKC (epsilon) and atypical PKC (mu) in the above brain regions were enriched by immunoprecipitation and later were assayed by Western blotting. The total, calcium-dependent and -independent PKC activities were determined by the radioactivity of total gamma-32P transferred to histone. The results indicated that on PND 1, Pb reduced the PKC-gamma protein in HC and FC, whereas on PND 5 the proteins of PKC isoforms (alpha, beta, gamma, epsilon, mu) in HC and FC were significantly reduced. These reductions in PKC proteins were higher in membrane fractions than in cytosolic fractions. On PND 10, Pb reduced all PKC isoforms. However, on PND 45, Pb had no significant effect on all PKC isoforms except epsilon. Pb inhibited the total PKC activity by 70% on PND 1 and 5, the bulk of these PKC activities were calcium-dependent. The results suggest that during early stages of the rat brain development, Pb exposure decreased PKC activities and also reduced PKC isoforms including PKC-gamma and epsilon which are reported to have roles in the memory formation and long-term potentiation (LTP).

Age Factors↗
PubMed2005

E-mail communications in primary care: what are patients' expectations for specific test results?

OBJECTIVES: The objectives of this study were to assess patients' willingness to use e-mail to obtain specific test results, assess their expectations regarding response times, and identify any demographic trends. METHODS: A cross-sectional survey of primary care patients was conducted in 19 clinics of a large multi-specialty group practice associated with an 186,000-member Health Maintenance Organization. The outcome measures were proportion of patients with current e-mail access, their willingness to use it for selected general clinical services and to obtain specific test results, and their expectations of timeliness of response. RESULTS: The majority of patients (58.3%) reported having current e-mail access and indicated strong willingness to use it for communication. However, only 5.8% reported having ever used it to communicate with their physician. Patients were most willing to use e-mail to obtain cholesterol and blood sugar test results, but less willing to use it to obtain brain CT scan results. Patients' expectations of timeliness were generally very high, particularly for high-stakes tests such as brain CT scan. Significant differences of willingness and expectations were found by age group, education, and income. CONCLUSIONS: These findings indicate that most patients are willing to use e-mail to communicate with their primary care providers even for specific test results and that patients will hold providers to high standards of timeliness regarding response. The implication is that integration of e-mail communications into primary care ought to assure prompt and accurate patient access to a plethora of specific clinical services.

Adult↗
PubMed2005

Protozoan genomes: gene identification and annotation.

The draft sequence of several complete protozoan genomes is now available and genome projects are ongoing for a number of other species. Different strategies are being implemented to identify and annotate protein coding and RNA genes in these genomes, as well as study their genomic architecture. Since the genomes vary greatly in size, GC-content, nucleotide composition, and degree of repetitiveness, genome structure is often a factor in choosing the methodology utilised for annotation. In addition, the approach taken is dictated, to a greater or lesser extent, by the particular reasons for carrying out genome-wide analyses and the level of funding available for projects. Nevertheless, these projects have provided a plethora of material that will aid in understanding the biology and evolution of these parasites, as well as identifying new targets that can be used to design urgently required drug treatments for the diseases they cause.

Algorithms↗