Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

Background and aimPatient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy.MethodsFirstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise.ResultsConsensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels.ConclusionsWe developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).     

Changes in glial fibrillary acidic protein mRNA expression after corticospinal axotomy in the adult hamster

We examined changes in the expression of glial fibrillary acidic protein (GFAP) mRNA during Wallerian degeneration in the corticospinal system of the adult Golden hamster following axotomy. GFAP is the product of a type III intermediate filament (IF) gene that is expressed specifically in mature astrocytes. A well-studied component of a complex response termed reactive astrogliosis that occurs after various types of CNS injury is the increased production of astrocytic processes filled with GFAP-containing IFs. While increased expression of GFAP during reactive astrogliosis has been well established at the protein level, little is known about whether or not changes in GFAP mRNA levels occur after CNS injury. In the present study we used in situ hybridization methods to examine this issue. A 35S-labeled mouse GFAP cDNA probe was used for in situ hybridizations of sections of the brain stem obtained 2, 7, and 14 days after unilateral transections of the corticospinal tract in the caudal medulla. Film as well as emulsion autoradiography showed a dramatic increase in GFAP mRNA labeling associated with the degenerating corticospinal tract. GFAP mRNA levels were already dramatically increased in the injured corticospinal tract by 2 days post axotomy and remained elevated at 14 days. Interestingly, in addition to the robust increase in GFAP mRNA levels specifically associated with the degenerating tract, a diffuse increase in GFAP mRNA labeling was observed throughout the grey matter of the brain stem at 2 days post-axotomy, but not after this time. Immunoblotting and immunocytochemical experiments verified that the increased GFAP mRNA levels in the degenerating corticospinal system were accompanied by an increased expression of the protein. These results demonstrate that an increase in GFAP mRNA levels occurs during Wallerian degeneration in the CNS and suggest that increased expression of the GFAP gene is a major contributor to CNS scarring that results after direct traumatic injury.     

Presence of beta human papillomaviruses in nonmelanoma skin cancer from organ transplant recipients and immunocompetent patients in the West of Scotland

Background  Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV).
Objectives  We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients.
Methods  One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction–reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes.
Results  In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples ( P  =   0·046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2–8). Tumours from IS patients were from a younger age group (mean age 57·4 years) than IC patients (mean age 73·8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) ( P  <   0·001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin.
Conclusions  A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.     

Detergent fractionation with subsequent subtractive suppression hybridization as a tool for identifying genes coding for plasma membrane proteins

Abstract:  The identification of tumor-specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post-translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane-associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane-associated proteins.     

Comparing histological data from different brains: Sources of error and strategies for minimizing them

The recent development of brain atlases with computer graphics templates, and of huge databases of neurohistochemical data on the internet, has forced a systematic re-examination of errors associated with comparing histological features between adjacent sections of the same brain, between brains treated in the same way, and between brains from groups treated in different ways. The long-term goal is to compare as accurately as possible a broad array of data from experimental brains within the framework of reference atlases. Main sources of error, each of which ideally should be measured and minimized, include intrinsic biological variation, linear and nonlinear distortion of histological sections, plane of section differences between each brain, section alignment problems, and sampling errors. These variables are discussed, along with approaches to error estimation and minimization in terms of a specific example—the distribution of neuroendocrine neurons in the rat paraventricular nucleus. Based on the strategy developed here, the main conclusion is that the best long-term solution is a high-resolution 3D computer graphics model of the brain that can be sliced in any plane and used as the framework for quantitative neuroanatomy, databases, knowledge management systems, and structure–function modeling. However, any approach to the automatic annotation of neuroanatomical data—relating its spatial distribution to a reference atlas—should deal systematically with these sources of error, which reduce localization reliability.     

In vivo electrochemical demonstration of potassium-evoked monoamine release from rat cerebellum

In vivo electrochemical methods were employed to study the potassium (K⁺-evoked release of monoamines from the cerebellum of the chloral hydrate anesthetized rat. K⁺-evoked releases were elicited using micropipette-Nafion-coated graphite epoxy electrode arrays in the granule/Purkenje cell layer, molecular layer, and white matter. These recorded releases were generally found to be reversible, moderately dose-dependent, and reproducible. However, the temporal dynamics of the releases were different for the cell layer versus molecular layer records. Releases were infrequently observed in cerebellar white matter, an area which is relatively devoid of monoamine containing terminals. The signals recorded from the cell and molecular layers were significantly attenuated by pretreatment with nomifensine, a potent catecholamine reuptake blocker, significantly prolonged the K⁺-evoked signals observed in both the granule/Purkenje cell and molecular layers. These data, taken together with earlier reports on the electrophysiological responses to activation of cerebellar noradrenergic inputs, support the conjecture that in vivo electrochemical recording methods have the sensitivity and spatial resolution for studies of functional monoamine release from brain regions that have a diffuse or laminated monoamine innervation.     

我院护士在职教育的体会

本文针对不同层次护理人员制定不同的培训目标和计划,采取岗前培训,岗位培训(专科培训、在职分层培训、护理人才培训),自学等形式,开展护士在职教育,不断扩充更新知识,以适应现代护理工作要求。