Tangible effects of the COVID-19 pandemic: A fall in dexterity amongst surgical trainees?

BACKGROUND: The coronavirus pandemic has had an indisputable impact on surgical training. The qualitative effect on the perceived confidence and capability of trainees has been widely reported. In order to fully delineate the scope of the problem, quantitative data is also required. METHODS: This cross-sectional study collected compared data on the laparoscopic skills (pre- and post-pandemic) of first-year urology residents in the United Kingdom, who attended the annual Urology Simulation Boot Camp (USBC) in 2018 and 2019 (pre-pandemic), and 2021 (post-pandemic). RESULTS: Pre-pandemic group performance was significantly better in 2 out of 4 tasks (Task 3 p < 0.001) (Task 4 p = 0.003) during the practice session. During the assessment, pre-pandemic group performance was better (p = 0.017) for Task 2 and significantly faster (p = 003) for Task 4. CONCLUSIONS: Our results provide evidence to support the notion that the coronavirus pandemic has had a tangible and detrimental effect on the technical skills of surgical trainees.

A Low-Cost Synthetic Abdominal Wall Model ("Raj Model") for the Training of Laparoscopic Port Insertion.

OBJECTIVE: To assess the content validity of a low-cost bench-top model ("Raj Model") for the training of laparoscopic port insertion at the Urology Simulation Bootcamp course (USBC). MATERIALS AND METHODS: A low-cost abdominal wall model of 40 × 40 cm was created to simulate laparoscopic port placement. The model was made using different synthetic materials to represent layers (skin-vinyl sheet, subcutaneous fat-10 mm soft foam, anterior rectus sheath and muscle-floor mat, posterior rectus sheath-masking wall tape, peritoneum-sellotape). Each model was used by up to 3 trainees to practise laparoscopic port placement. The model was assessed for content validity by trainees and experts using a 5-point Likert scale. RESULT: In total, 88 trainees and 6 experts participated in the study. For all aspects of the synthetic abdominal wall, good (4) or very good (5) scores ranged from 52.7-69.2%, whereas very poor (1) rating ranged from 0 to 4.3%. There was no significant difference in responses for the content validity of the model between trainees and experts. There was a high intraclass correlation amongst responses from trainees (0.89) and experts (0.79). Approximately 76.3% of trainees and experts felt that the model is suitable for training. CONCLUSION: This is the first validation study of a low-cost abdominal wall model for teaching laparoscopic port placement for trainees. Our study demonstrates that this synthetic model has high content validity and is useful for surgical training.

T-cell signalling and immune system disorders.

T-cell receptor (TCR) engagement initiates intracellular signalling cascades that lead to T-cell proliferation, cytokine production and differentiation into effector cells. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions. The integration of these signals is essential for the normal development, homeostasis and function of T cells. Defects in a single mediator can produce T cells that are unable to participate fully in an immune response and/or that mount an inappropriate response, which leads to immunodeficiency, autoimmunity or leukaemia/lymphomas. This review highlights some of the key players in T-cell signalling and their involvement in the development of various clinical disease states. Some of these immune-specific signalling proteins are attractive potential targets in the development of therapies to augment T-cell responses to antigen or tumours, and to treat immune cell disorders.

An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection.

Positive selection of developing thymocytes is associated with changes in cell function, at least in part caused by alterations in expression of cell surface proteins. Surprisingly, however, few such proteins have been identified. We have analyzed the pattern of gene expression during the early stages of murine thymocyte differentiation. These studies led to identification of a cell surface protein that is a useful marker of positive selection and is a likely regulator of mature lymphocyte and APC function. The protein is a member of the Ig superfamily and contains conserved tyrosine-based signaling motifs. The gene encoding this protein was independently isolated recently and termed B and T lymphocyte attenuator (Btla). We describe in this study anti-BTLA mAbs that demonstrate that the protein is expressed in the bone marrow and thymus on developing B and T cells, respectively. BTLA is also expressed by all mature lymphocytes, splenic macrophages, and mature, but not immature bone marrow-derived dendritic cells. Although mice deficient in BTLA do not show lymphocyte developmental defects, T cells from these animals are hyperresponsive to anti-CD3 Ab stimulation. Conversely, anti-BTLA Ab can inhibit T cell activation. These results implicate BTLA as a negative regulator of the activation and/or function of various hemopoietic cell types.

TOX provides a link between calcineurin activation and CD8 lineage commitment.

T cell development is dependent on the integration of multiple signaling pathways, although few links between signaling cascades and downstream nuclear factors that play a role in thymocyte differentiation have been identified. We show here that expression of the HMG box protein TOX is sufficient to induce changes in coreceptor gene expression associated with beta-selection, including CD8 gene demethylation. TOX expression is also sufficient to initiate positive selection to the CD8 lineage in the absence of MHC-TCR interactions. TOX-mediated positive selection is associated with up-regulation of Runx3, implicating CD4 silencing in the process. Interestingly, a strong T cell receptor-mediated signal can modify this cell fate. We further demonstrate that up-regulation of TOX in double positive thymocytes is calcineurin dependent, linking this critical signaling pathway to nuclear changes during positive selection.

Staging in prostate cancer.

This article reviews the conventional current techniques that are used for staging prostate cancer. The advantages and limitations of each modality are described. Attention is focused on the areas in which progress is rapidly being made and is likely to be developed in the future.

TOX: an HMG box protein implicated in the regulation of thymocyte selection.

In the thymus, pre-T cell receptor (pre-TCR)--mediated signaling and then TCR-mediated signaling initiate changes in gene expression that result in the maturation of CD4 and CD8 lineage T cells from common precursors. Using gene chip technology, we isolated a murine gene, designated Tox, that encodes a member of the HMG (high-mobility group) box family of DNA-binding proteins. TOX expression is up-regulated by both pre-TCR and TCR activation of immature thymocytes but not by TCR activation of mature naïve T cells. Transgenic mice that express TOX show expanded CD8+ and reduced CD4+ single positive thymocyte subpopulations. We present evidence here that this phenotype results from a perturbation in lineage commitment due to reduced sensitivity to TCR-mediated signaling. This molecular marker of thymic selection events may therefore play a role in establishing the activation threshold of developing T cells and patterning changes in gene expression.