Skeletal muscle transcriptomics of sheep acclimated to cold desert and tropical regions identifies genes and pathways accentuating their diversity.

The current study attempts to investigate the differences in gene expression in longissimus thoracis muscles between sheep breeds acclimated to diverse environments. Changthangi sheep inhabits the cold arid plateau of Ladakh, at an altitude above 3000 m with prevalence of rarefied atmosphere. Muzzafarnagri sheep, on the other hand is found in the sub-tropical hot and humid plains at an altitude of about 250 m. Comparative transcriptomics was used to provide a molecular perspective of the differential adaptation of the two breeds. RNA sequencing data was generated from four biological replicates of the longissimus thoracis muscles from both breeds. The common genes expressed in both breeds were involved in muscle contraction and muscle fibre organization. The most significant pathways enriched in Changthangi muscles were glycogen metabolism, reduction of cytosolic Ca++ levels and NFE2L2 regulating anti-oxidant, while those in Muzzafarnagri were extracellular matrix organization and collagen formation. The hub genes identified in Changthangi were involved in hematopoiesis and HIF signaling pathway, suggesting the molecular acclimatization of Changthangi to the high altitude cold desert of Ladakh. The nodal genes discovered in Muzzafarnagri sheep were associated with the extracellular matrix which accentuates its significance in the development, growth and repair of muscles. The observed transcriptomic differences underscore the morphological and adaptive disparity between the two breeds. The candidate genes and pathways identified in this study will form the basis for future research on adaptation to high altitude and body size in small ruminants.

"We Need More Practice": Evaluating the Role of Virtual Mock OSCES in the Undergraduate Programme During the COVID Pandemic.

Background: Feedback collated at University College London Medical School (UCLMS) during the COVID pandemic identified how many students felt unprepared for their summative Objective Structured Clinical Examinations (OSCEs) despite attending mock face-to-face OSCEs. The aim of this study was to explore the role of virtual mock OSCES for improving student's sense of preparedness and confidence levels for their summative OSCEs. Methods: All Year 5 students (n=354) were eligible to participate in the virtual mock OSCEs and were sent a pre- and post-survey for completion. Hosted on Zoom in June 2021, each circuit comprised six stations, assessing history taking and communication skills only, in Care of the Older Person, Dermatology, Gynaecology, Paediatrics, Psychiatry and Urology. Results: Two hundred and sixty-six Year 5 students (n=354) participated in the virtual mock OSCEs, with 84 (32%) students completing both surveys. While a statistically significant increase in preparedness was demonstrated, there was no difference in overall confidence levels. In contrast, between specialties, a statistically significant increase in confidence levels was seen in all specialties barring Psychiatry. Despite half of the participants highlighting how the format did not sufficiently represent the summative OSCEs, all expressed interest in having virtual mock OSCEs incorporated into the undergraduate programme. Conclusion: The findings of this study suggest that virtual mock OSCEs have a role in preparing medical students for their summative exams. While this was not reflected in their overall confidence levels, this may be due to a lack of clinical exposure and higher anxiety levels among this cohort of students. Although virtual OSCEs cannot replicate the "in-person" experience, considering the logistical advantages, further research is required on how these sessions can be developed, to support the traditional format of face-to-face mock OSCEs within the undergraduate programme.

Evolving Role of Magseed in Wireless Localization of Breast Lesions: Systematic Review and Pooled Analysis of 1,559 Procedures.

BACKGROUND/AIM: Wire-guided localisation (WGL) remains the most widely used technique for the localisation of non-palpable breast lesions; however, recent technological advances have resulted in non-wire, non-radioactive alternatives, such as magnetic seeds (Magseeds). The aim of this pooled analysis was to determine whether Magseeds are an effective tool for localising non-palpable breast lesions. MATERIALS AND METHODS: Various databases were searched for publications which reported data on the localisation and placement rates of Magseed. Data on re-excision rates under use of Magseed and WGL were also collected. RESULTS: Sixteen studies, spanning the insertion of 1,559 Magseeds, were analysed. The pooled analysis showed a successful placement rate of 94.42% and a successful localisation rate of 99.86%. Four studies were analysed in a separate pooled analysis and showed no statistically significant difference between re-excision rates using Magseeds and WGL. CONCLUSION: The use of Magseeds is an effective, non-inferior alternative to WGL that overcomes many of the limitations of the latter.

Locoregional therapy of the primary tumour in de novo stage IV breast cancer in 216 066 patients: A meta-analysis.

Patients presenting with de novo stage IV metastatic breast cancer have a complex disease which is normally treated with palliative intent and systemic therapy. However, there is mounting evidence that resection of the primary tumour and/or localised radiotherapy (locoregional therapy; LRT) could be associated with overall survival improvements. We aimed to conduct a meta-analysis to inform decision making. Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis were conducted to assess the effect of LRT on overall survival. Studies were analysed for the impact of LRT on survival. All forms of LRT resulted in a significant 31.8% reduction in mortality (N = 42; HR = 0.6823 (95% CI 0.6365; 0.7314)). Surgical resection resulted in a significant 36.2% reduction in mortality (N = 37; HR = 0.6379 (95% CI 0.5974; 0.6811)). The prospective trials reported a 19.23% reduction in mortality which was not statistically significant (N = 3, HR = 0.8077 (95% CI 0.5704; 1.1438). 216 066 patients were included. This is the largest meta-analysis regarding this question to date. Our meta-analysis shows that LRT of the primary tumour seems to improve overall survival in de novo stage IV disease. Therefore, this therapeutic option should be considered in selected patients after a careful multidisciplinary discussion.

The Use of Magnetic Seeds and Radiofrequency Identifier Tags in Breast Surgery for Non-palpable Lesions.

BACKGROUND: Wire-guided localisation (WGL) remains the most widely used technique to guide surgical excision of non-palpable breast lesions worldwide. However, recent technological advances have led to the advent of less invasive radiation-free localisation methods to overcome the limitations of WGL. PATIENTS AND METHODS: This study prospectively evaluated the role of two radiation-free non-wire localisation methods. Magnetic seeds (n=16) and radiofrequency tags (n=6) were deployed under imaging guidance to guide the surgical excision in 19 consecutive patients. RESULTS: The identification/retrieval and migration rates were 100% and 4.5%, respectively. Twenty-one out of 22 (95.5%) cases had clear surgical margins and no complications were observed. All radiologists and the surgeon rated these methods as being much better than wire localisation. Patient satisfaction data were recorded using a linear visual analogue scale (n=10/19). The mean score was 9.7/10 (range=8-10). CONCLUSION: Our study provides further evidence that radiation-free wireless breast localisation is an effective alternative to WGL.

Does Transdermal Testosterone Increase the Risk of Developing Breast Cancer? A Systematic Review.

BACKGROUND/AIM: Hypoactive sexual desire disorder (HSDD) is hypothesised to manifest in postmenopausal women at onset of menopause due to decreased oestrogen levels. Transdermal testosterone is a potential treatment option. This systematic review explores the relationship between the incidence of breast cancer and transdermal testosterone use. MATERIALS AND METHODS: Searches were conducted on the PubMed and Ovid databases. In Ovid, the advanced search function was used: 'transdermal testosterone not male'. In PubMed, the following search terms were used: 'transdermal, testosterone, menopausal, women, breast cancer, women'. Abstracts that fitted our initial criteria were further investigated. RESULTS: A total of 25 publications from PubMed and 192 publications from Ovid were initially assessed. Three randomised control trials were judged to have sufficiently met our inclusion criteria. However, these trials were too heterogeneous for a meta-analysis. A systematic review was deemed the most appropriate analysis of the data available. CONCLUSION: The publications examined in this systematic review suggest that the use of transdermal testosterone to treat HSDD in postmenopausal women does not increase breast cancer incidence. However, further research in the form of adequately powered randomised controlled trials with breast cancer incidence being the primary end point is required in order to confirm this.

Can Complete Axillary Node Dissection Be Safely Omitted in Patients with Early Breast Cancer When the Sentinel Node Biopsy Is Positive for Malignancy? An Update for Clinical Practice.

The sentinel lymph node biopsy (SLNB) has become the new standard-of-care for patients with clinically node-negative invasive breast cancer. The focused examination of fewer lymph nodes in addition to improvements in histopathological and molecular analysis have increased the rate at which micrometastases and isolated tumor cells are identified. We reviewed the literature and summarized the evidence regarding the need for complete axillary lymph node dissection (ALND) following the finding of a positive sentinel node biopsy through the identification of the most important outcomes and evaluation of quality of evidence. The article focuses on the safe omission of complete ALND when the axillary lymph nodes contain macrometastases and provides an overview of the topic primarily based on level 1 evidence derived from randomized clinical trials with a critical appraisal of the ACOSOG Z0011 trial.

mRNA Expression of CDK2AP1 in Human Breast Cancer: Correlation with Clinical and Pathological Parameters.

BACKGROUND: Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. Our objective was to determine if CDK2AP1 mRNA expression levels were consistent with tumour-suppressive functions in breast cancer. MATERIALS AND METHODS: A total of 134 samples were analysed. CDK2AP1 mRNA levels were measured using quantitative polymerase chain reaction (RT-PCR) and normalised against glyceraldehyde 3-phosphate dehydrogenase mRNA. Levels in breast cancer and adjacent non-cancerous breast tissue were analysed against pathological and clinical parameters (TNM staging, survival over a 10-year follow-up period). RESULTS: Normalised CDK2AP1 expression was 38-fold higher in adjacent non-cancerous breast tissue than in breast cancer. CDK2AP1 expression in disease-free patients at 10 years was more than threefold that of patients who died of breast cancer. However, neither of these differences in expression levels reached statistical significance. CDK2AP1 mRNA levels were higher in TNM1 compared to TNM3 (p=0.016) and with TNM4 (p=0.016). There were no significant associations between CDK2AP1 expression and estrogen receptor status, tumour grade and tumour type. There was no significant difference in overall survival between patients with high and those with low CDK2AP1 mRNA levels after a median follow-up of 10 years (Kaplan-Meier analysis, p=0.872). CONCLUSION: To our knowledge, this is the first study in the literature to examine the mRNA expression of CDK2AP1 in human breast cancer over a long-term follow-up period. A compelling relationship exists between high CDK2AP1 mRNA expression and lower TNM classification of breast cancer, which is consistent with CDK2AP1 having a tumour-suppressive function.

Does the Use of Hair Dyes Increase the Risk of Developing Breast Cancer? A Meta-analysis and Review of the Literature.

BACKGROUND/AIM: Hair dye may contain mutagenic compounds which could be associated with an increased incidence of breast cancer in women who use it. The aim of this study was to examine the association between the personal use of hair dyes and the risk of breast cancer. MATERIALS AND METHODS: We conducted a literature review of epidemiological studies reporting breast cancer-specific risks among hair dye users versus non-users. The data for the incidence of breast cancer following the 'ever' use of hair dye in studies which met the inclusion criteria was analysed using a meta-analysis. The relative risk ratio (RR) and 95% confidence intervals (CI) were determined. RESULTS: A total of eight case-control studies published between 1980 and 2017 met the selection criteria and were included in the meta-analysis. Compared to non-users, using a random effects model and the Duval and Tweedie's trim and fill procedure to adjust for publication bias in the presence of between studies heterogeneity, the adjusted RR for women using hair dyes was 1.1885 (95% CI=1.03228-1.36835). This indicates an 18.8% increased risk of future development of breast cancer among hair dye users. CONCLUSION: Although further work is required to confirm our results and clarify potential mechanisms, our findings suggest that exposure to hair dyes may contribute to an increased breast cancer risk.