Exercise and Heat Stress in Well-Healed Burn Survivors:Effects of Cooling Modalities on Thermal and Perceptual Responses

PURPOSE: Burn injuries that require grafting impair thermoregulation, which may dissuade individuals with such injuries from being physically active. We tested the hypothesis that cooling modalities attenuate core temperature elevations and perceptions of heat stress during physical activity in the heat among adults with well-healed burn injuries.METHODS: Adults with no burn injuries (non-burned), 20-40% body surface area burn injuries (moderate burn), and &gt; 40% body surface area burn injuries (large burn) performed 1 hour of moderate intensity exercise (2.5 ± 0.2 mph and 2% grade) on four different occasions in two environmental conditions (30 °C &amp; 39 °C, 40% relative humidity). Within each environmental condition, we applied one of the following cooling modalities, random assigned, for each visit: no cooling (control), fan at 4 m/s (fan), water spray every 5 min (water spray; scaled to burn area size), or a combination of water spray + fan.RESULTS: In 30 °C, perceptual strain index (PeSI) was reduced in the non-burned and moderate burn groups with water spray + fan, whereas PeSI was reduced with all cooling modalities in the large burn group. The cooling modalities did not affect core temperature responses. In the 39 °C environment, water spray and water spray + fan attenuated the elevation in core temperature (p ≤ 0.007) only in the large burn group. In the moderate burn group, PeSI was decreased with water spray + fan (p = 0.017). In the large burn group, both water spray alone and water spray + fan (p ≤ 0.041) lowered PeSI.CONCLUSIONS: For both environments across burn groups, the applied cooling modalities were generally more effective at reducing indices of perceptual strain relative to indices of thermal strain (e.g., core temperature).</p

Development and assessment of a 3D tooth morphology quiz for dental students

Tooth morphology has a pivotal role in the dental curriculum and provides one of the important foundations of clinical practice. To supplement tooth morphology teaching a three‐dimensional (3D) quiz application (app) was developed. The 3D resource enables students to study tooth morphology actively by selecting teeth from an interactive quiz, modify their viewpoint and level of zoom. Additionally, students are able to rotate the tooth to obtain a 3D spatial understanding of the different surfaces of the tooth. A cross‐over study was designed to allow comparison of students’ results after studying with the new application or traditionally with extracted/model teeth. Data show that the app provides an efficient learning tool and that students’ scores improve with usage (18% increase over three weeks, P < 0.001). Data also show that student assessment scores were correlated with scores obtained while using the app but were not influenced by the teaching modality initially accessed (r2 = 0.175, P < 0.01). Comparison of the 2016 and 2017 class performance shows that the class that had access to the app performed significantly better on their final tooth morphology assessment (68.0% ±15.0 vs. 75.3% ±13.4, P < 0.01). Furthermore, students reported that the 3D application was intuitive, provided useful feedback, presented the key features of the teeth, and assisted in learning tooth morphology. The 3D tooth morphology app thus provides students with a useful adjunct teaching tool for learning dental anatomy

Recent advances in the understanding of the aetiology and therapeutic strategies in burning mouth syndrome: Focus on the actions of cannabinoids

Burning mouth syndrome (BMS) is a neuropathic pain disorder associated with a burning sensation on oral mucosal surfaces with frequently reported xerostomia, dysgeusia and tingling or paraesthetic sensations. However, patients present no clinically evident causative lesions. The poor classification of the disorder has resulted in a diagnostic challenge, particularly for the clinician/dentist evaluating these individuals. Major research developments have been made in the BMS field in recent years to address this concern, principally in terms of the pathophysiological mechanisms underlying the disorder, in addition to therapeutic advancements. For the purpose of this review, an update on the pathophysiological mechanisms will be discussed from a neuropathic, immunological, hormonal and psychological perspective. This review will also focus on the many therapeutic strategies that have been explored for BMS, including antidepressants/antipsychotics, nonsteroidal anti-inflammatories, hormone replacement therapies, phytotherapeutic compounds and non-pharmacological interventions, overall highlighting the lack of controlled clinical studies to support the effectiveness of such therapeutic avenues. Particular focus is given to the cannabinoid system, and the potential of cannabis-based therapeutics in managing BMS patients

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species

Comparing mutation calls in fixed tumour samples between the Affymetrix OncoScan® Array and PCR based next-generation sequencing

Background: The importance of accurate and affordable mutation calling in fixed pathology samples is becoming increasingly important as we move into the era of personalised medicine. The Affymetrix OncoScan® Array platform is designed to produce actionable mutation calls in archival material. Methods: We compared calls made using the OncoScan platform with calls made using a custom designed PCR panel followed by next-generation sequencing (NGS), in order to benchmark the sensitivity and specificity of the OncoScan calls in a large cohort of fixed tumour samples. 392 fixed, clinical samples were sequenced, encompassing 641 PCR regions, 403 putative positive calls and 1528 putative negative calls. Results: A small number of mutations could not be validated, either due to large indels or pseudogenes impairing parts of the NGS pipeline. For the remainder, if calls were filtered according to simple quality metrics, both sensitivity and specificity for the OncoScan platform were over 98%. This applied even to samples with poorer sample quality and lower variant allele frequency (5–10%) than product claims indicated. Conclusions: This benchmarking study will be useful to users and potential users of this platform, who wish to compare technologies or interpret their own results

Novel Role of Prostate Apoptosis Response-4 Tumor Suppressor in B-Cell Chronic Lymphocytic Leukemia

Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell-cycle transition. Lack of Par-4 also increased the expression of p21 and delayed CLL growth in Eμ-Tcl1 mice. Par-4 expression in CLL cells required constitutively active B-cell receptor (BCR) signaling, as inhibition of BCR signaling with US Food and Drug Administration (FDA)–approved drugs caused a decrease in Par-4 messenger RNA and protein, and an increase in apoptosis. In particular, activities of Lyn, a Src family kinase, spleen tyrosine kinase, and Bruton tyrosine kinase are required for Par-4 expression in CLL cells, suggesting a novel regulation of Par-4 through BCR signaling. Together, these results suggest that Par-4 may play a novel progrowth rather than proapoptotic role in CLL and could be targeted to enhance the therapeutic effects of BCR-signaling inhibitors