PR-Set7 is Degraded in a Conditional Cul4A Transgenic Mouse Model of Lung Cancer.

BackgroundMaintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage.MethodsWe developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC.ResultsThe level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre.ConclusionsPR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model

A report on an exploratory study on visual conditions of older people living in public housing

HOPE worldwide (HWW) has been a chartered charity organization in Hong Kong since 1993, with its focus on organizing service programmes in China and Hong Kong. Volunteers for Seniors Day (formerly Hope for Seniors Day) is one of the many programmes initiated by HWW to meet the urgent needs of the growing ageing population in Hong Kong. Starting in 1996, volunteers from corporations and social organizations have been recruited for Volunteers for Seniors Days on an annual basis. Since 2000, the programme has been jointly organized with the Housing Authority to provide cleaning and painting services to single elderly tenants living in public housing estates. It also helps to build relationships between the volunteers and the elderly people in the community. Over the past nine years, the programme has served over 5,300 single elderly people and mobilized more than 20,000 volunteers to participate. In the survey conducted by HWW during Volunteers for Seniors Day 2004, we found that there were up to 40.1% and 49.6% of the single elderly living in public housing estates suffering from various kinds of eye diseases and poor eyesight respectively. The prevalence of eye diseases and poor eyesight would result in a high percentage of falls and thereby affect their functional activities of daily living (ADL). In fact, most of the eye diseases are curable with early detection and treatment, and elderly people with poor eyesight may need minor home adaptation e.g. handrails or night lights to prevent home accidents. According to a study by the Department of Orthopaedics & Traumatology of Chinese University, exercise is important to the elderly and can strengthen their low-limb and upper-limb muscles, which in turn prevents falls at home or on the street. Due to the above findings, HWW cooperated with Housing Authority to initiate a pilot programme to help identify the eye diseases as well as provide public health education to the elderly in 30 public estates in the second half of 2004. Health care professionals provided training to 150 volunteers on eye care knowledge and simple eye screening tests that could be carried out in road shows in shopping arcades of public housing estates. In addition, experienced ophthalmologists or optometrists were present to answer elderly participants’ inquiries on eye health and delivered health information during the kick-off ceremony and road shows in the shopping arcades. The programme had the following objectives: To enhance the awareness of eye health and eye diseases of the elderly through 30 public eye screenings at public housing arcades; To carry out a survey on the visual conditions of elderly living in public housing; and To foster partnership between government, NGO and business sectors in promoting the health of the elderly in the community

International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) - the propagation of knowledge in ultrasound for the improvement of OB/GYN care worldwide: experience of basic ultrasound training in Oman.

BACKGROUND: The aim of this study is to evaluate effectiveness of a new ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) Outreach Teaching and Training Program delivered in Muscat, Oman. METHODS: Quantitative assessments to evaluate knowledge and practical skills were administered before and after an ultrasound course for sonologists attending the ISUOG Outreach Course, which took place in November, 2017, in Oman. Trainees were selected from each region of the country following a national vetting process conducted by the Oman Ministry of Health. Twenty-eight of the participants were included in the analysis. Pre- and post-training practical and theoretical scores were evaluated and compared. RESULTS: Participants achieved statistically significant improvements, on average by 47% (p < 0.001), in both theoretical knowledge and practical skills. Specifically, the mean score in the theoretical knowledge test significantly increased from 55.6% (± 14.0%) to 81.6% (± 8.2%), while in the practical test, the mean score increased from 44.6% (± 19.5%) to 65.7% (± 23.0%) (p < 0.001). Performance was improved post-course among 27/28 participants (96.4%) in the theoretical test (range: 14 to 200%) and among 24/28 (85.7%) trainees in the practical skills test (range: 5 to 217%). CONCLUSION: Application of the ISUOG Basic Training Curriculum and Outreach Teaching and Training Course improved the theoretical knowledge and practical skills of local health personnel. Long-term re-evaluation is, however, considered imperative to ascertain and ensure knowledge retention

AI chatbots not yet ready for clinical use

As large language models (LLMs) expand and become more advanced, so do the natural language processing capabilities of conversational AI, or “chatbots”. OpenAI's recent release, ChatGPT, uses a transformer-based model to enable human-like text generation and question-answering on general domain knowledge, while a healthcare-specific Large Language Model (LLM) such as GatorTron has focused on the real-world healthcare domain knowledge. As LLMs advance to achieve near human-level performances on medical question and answering benchmarks, it is probable that Conversational AI will soon be developed for use in healthcare. In this article we discuss the potential and compare the performance of two different approaches to generative pretrained transformers—ChatGPT, the most widely used general conversational LLM, and Foresight, a GPT (generative pretrained transformer) based model focused on modelling patients and disorders. The comparison is conducted on the task of forecasting relevant diagnoses based on clinical vignettes. We also discuss important considerations and limitations of transformer-based chatbots for clinical use

Measurement agreement between a newly developed sensing insole and traditional laboratory-based method for footstrike pattern detection in runners

This study introduced a novel but simple method to continuously measure footstrike patterns in runners using inexpensive force sensors. Two force sensing resistors were firmly affixed at the heel and second toe of both insoles to collect the time signal of foot contact. A total of 109 healthy young adults (42 males and 67 females) were recruited in this study. They ran on an instrumented treadmill at 0˚, +10˚, and -10˚ inclinations and attempted rearfoot, midfoot, and forefoot landings using real time visual biofeedback. Intra-step strike index and onset time difference between two force sensors were measured and analyzed with univariate linear regression. We analyzed 25,655 footfalls and found that onset time difference between two sensors explained 80–84% of variation in the prediction model of strike index (R-squared = 0.799–0.836, p<0.001). However, the time windows to detect footstrike patterns on different surface inclinations were not consistent. These findings may allow laboratory-based gait retraining to be implemented in natural running environments to aid in both injury prevention and performance enhancement

Serial expression analysis of breast tumors during neoadjuvant chemotherapy reveals changes in cell cycle and immune pathways associated with recurrence and response

Abstract Introduction The molecular biology involving neoadjuvant chemotherapy (NAC) response is poorly understood. To elucidate the impact of NAC on the breast cancer transcriptome and its association with clinical outcome, we analyzed gene expression data derived from serial tumor samples of patients with breast cancer who received NAC in the I-SPY 1 TRIAL. Methods Expression data were collected before treatment (T1), 24–96 hours after initiation of chemotherapy (T2) and at surgery (TS). Expression levels between T1 and T2 (T1 vs. T2; n = 36) and between T1 and TS (T1 vs. TS; n = 39) were compared. Subtype was assigned using the PAM50 gene signature. Differences in early gene expression changes (T2 − T1) between responders and nonresponders, as defined by residual cancer burden, were evaluated. Cox proportional hazards modeling was used to identify genes in residual tumors associated with recurrence-free survival (RFS). Pathway analysis was performed with Ingenuity software. Results When we compared expression profiles at T1 vs. T2 and at T1 vs. TS, we detected significantly altered expression of 150 and 59 transcripts, respectively. We observed notable downregulation of proliferation and immune-related genes at T2. Lower concordance in subtype assignment was observed between T1 and TS (62 %) than between T1 and T2 (75 %). Analysis of early gene expression changes (T2 − T1) revealed that decreased expression of cell cycle inhibitors was associated with poor response. Increased interferon signaling (TS − T1) and high expression of cell proliferation genes in residual tumors (TS) were associated with reduced RFS. Conclusions Serial gene expression analysis revealed candidate immune and proliferation pathways associated with response and recurrence. Larger studies incorporating the approach described here are warranted to identify predictive and prognostic biomarkers in the NAC setting for specific targeted therapies. Clinical trial registration ClinicalTrials.gov identifier: NCT00033397 . Registered 9 Apr 2002

Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ.

Myoepithelial cells play key roles in normal mammary gland development and in limiting pre-invasive to invasive breast tumor progression, yet their differentiation and perturbation in ductal carcinoma in situ (DCIS) are poorly understood. Here, we investigated myoepithelial cells in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls, and in sporadic DCIS. We found that in the normal breast of non-carriers, myoepithelial cells frequently co-express the p63 and TCF7 transcription factors and that p63 and TCF7 show overlapping chromatin peaks associated with differentiated myoepithelium-specific genes. In contrast, in normal breast tissues of BRCA1 mutation carriers the frequency of p63+TCF7+ myoepithelial cells is significantly decreased and p63 and TCF7 chromatin peaks do not overlap. These myoepithelial perturbations in normal breast tissues of BRCA1 germline mutation carriers may play a role in their higher risk of breast cancer. The fraction of p63+TCF7+ myoepithelial cells is also significantly decreased in DCIS, which may be associated with invasive progression

麻雀治療實務手冊

本港人口正急速老化，65歲以上的老年人口將在未來三十年佔總人口的四分之一。如何確保長者的生活質素，以及提升護老者的照顧能力，將會是未來香港社會的挑戰。過去十年，各政府部門、醫管局、大學、專業團體和社會服務機構，都致力發展和研究有關老年健康的課題，藉以提升長者的生理、認知、心理和社交健康。近年，很多從西方引入的治療研究，亦被嘗試應用在不同類型的疾病上，例如：懷緬治療、多感觀治療、音樂治療和認知行為治療等，但應用在華人身上的成效，則有待更多的驗證。 華人社會一向重視家庭和親屬關係，以及勤奮工作的文化。大部份長者的教育水平偏低，年青時都只着重工作，甚少娛樂；跳舞、上戲院、閱讀、攝影只是少部份長者的嗜好，普羅大眾的娱樂文化主要是往茶樓品茗、打麻雀、打天九、看電視和賭博等等。麻雀治療是從長者過往較多接觸的活動中，發展出來的一套具有本土特色而非使用藥物的治療方法，旨意在融入長者的日常生活中，達到既提供娛樂活動，亦同時提升長者的身體、認知、心理和社交功能。 傳統的中國文化，一直流傳著所謂「打麻雀能醫百病」、「打麻雀是一種心靈寄託」、「打麻雀可以使人忘記煩惱、病痛」等說法。而每逢節日和家人團聚，“打幾圈”麻雀已成為一種很普及的娛樂活動。最近，有些報導以及一些醫生均指出打麻雀有助老年人避免患上心理疾病，以及減輕老年痴呆症患者的退化症狀。然而，上述的觀點至今仍未有科學方面的引證。 在2004年，仁濟醫院社會服務部與嶺南大學亞太老年學研究中心,採用科學化的研究方法，於仁濟醫院社會服務部轄下八間老人院舍中，選取121位患有輕度及中度認知能力受損的長者進行麻雀治療的研究。研究的目的是希望引證麻雀治療能否改善患有老年痴呆症長者的身體、認知、心理和社交功能，並找出一套具策劃及有效執行的麻崔治療模式。透過研究的經驗和成果，將麻雀活動發展成為一稱具本土特色的健康治療工具。我們盼望藉此實務手冊，為年長一聚提供多一個非藥物的治療選擇；同時亦希望本手冊能夠發揮拋縛引玉的效果，使各界人士能夠繼續推廣和實行麻雀治療，造福廣大的社群。https://commons.ln.edu.hk/apias_guide/1000/thumbnail.jp

Older women, breast cancer, and social support

One in ten women over the age of 65 will develop breast cancer. Despite this high incidence of breast cancer among older women, social support for them is often inadequate. This paper describes a qualitative study of the impact of a breast cancer diagnosis on older women from racially/ethnically diverse populations and their subsequent need for social support. Forty-seven older African American, Asian American, Caucasian and Latina women between the ages of 65 to 83 participated in a larger study examining the impact of breast cancer on women from racially/ethnically diverse populations and the meaning and nature of social support. The women completed an in-depth qualitative interview on the psychosocial impact of breast cancer and the meaning and nature of social support. The results indicate that there are variations in reactions to a breast cancer diagnosis among older women, and that these reactions impact their experiences with seeking social support at diagnosis and during treatment. Respondents were concerned about their aging bodies, potential dependency on others, and loss of autonomy. At the same time, the severity of cancer treatment and existing co-morbidities often meant they needed to learn to receive support, and to reach out if they had no support. The implications of these findings underscore the older cancer patient’s need to strengthen her supportive networks at the time of diagnosis, during treatment, and post-treatment