乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Evaluation of a range of hospital replacement mattresses

A combination of physical measurement and clinical testing was used to evaluate a range of pressure-reducing replacement mattresses, which had met tender specifications, in order to reduce the number available for selection in the purchasing process. Factors considered included mattress price and expected life-span. The results presented have supported a purchasing decision to replace mattresses but care should be taken in adopting these findings in a different context from that of a district general hospital. Optimum performance was found in one mattress replacement (Pentaflex).     

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

Nonviral delivery of self-amplifying RNA vaccines

Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.     

Phase 2 of collaborative action around the implementation of virtual hearing aid care: Evaluation of a clinical practice guideline

Rationale

Following the onset of the COVID-19 pandemic, a clinical practice guideline (CPG) around virtual hearing aid practices was developed to fill a knowledge gap within the field of audiology. Details outlining the development and mobilization of this draft guideline were outlined as Phase 1 (described in a paired paper).

Aims and Objectives

This study describes Phase 2 of this project as part of the Knowledge-to-Action Framework, including an evaluation of the methodological quality of the guideline and the resulting tailored version of the document (v2.0).

Method

The Appraisal of Guidelines for Research and Evaluation II instrument was used to assess methodological quality and to guide revisions. Twenty-two clinicians, from a variety of clinical backgrounds, participated in the evaluation.

Results and Conclusion

Findings reported across six domains suggest high mean scores, ranging from 78% to 81%, in order of scope and purpose (highest rated), stakeholder involvement, rigour of development, applicability, clarity of presentation, and editorial independence. Specific recommendations made by in international co-creation team during the evaluation informed the final version of the CPG. Future development and evaluation efforts should aim to include greater representation from nontraditional practice contexts to strengthen global applicability.     

Food label reading and understanding in parts of rural and urban Zimbabwe

Background

Overweight and obesity prevalence is rapidly rising in developing countries. The reading and understanding of nutrition information on food packages has been shown to improve food choices and instill healthy eating habits in individuals.

Objective

The aim of this study was to describe the prevalence of food label usage and understanding among urban and rural adults in Zimbabwe and its association with demographic and socio economic factors.

Methods

A cross sectional study was conducted on 320 adults (147 urban and 173 rural) using a validated questionnaire adapted from previous similar studies. Data were analysed using SPSS-17 statistical software.

Results

A high proportion (77.2%) of the respondents read food labels. Food label reading differed significantly by educational status (p<0.05), employment status (p<0.05) and locality (p<0.05). Only 40.9% of food label readers mostly understood the information on the food labels. More urban shoppers (86.1%) read food labels than their rural counterparts (66.7%). A significant number of participants (80.6%) indicated they would like to be educated on the meaning of food labels and 80.3% preferred the nutrition information on food labels to be simplified.

Conclusion

The study found above average reported reading of nutrition information on food labels with partial understanding. Efforts should be made to determine how all consumers could be made to understand the nutrition information on food labels and use it effectively in decision making.