The diathermy scratch pad: A cheap and efficient tool for chemical and explosion-related burns

The burn center in our hospital is a national and regional (Southeast Asia) center. Of all admissions, 10% are related to blast explosions, and 8% due to chemical burns. In the acute burn management protocol of Singapore General Hospital, early surgical debridement is advocated for all acute partial-thickness burns. The aim of early surgical debridement is to remove all debris and unhealthy tissue, preventing wound infection and thereby expediting wound healing. In chemical burns, there can be stubborn eschars that are resistant to traditional debridement. We would like to present a novel technique using the diathermy scratch pad as a cheap and efficient tool for the dual purpose of surgical debridement and dermabrasion

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction

Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure–activity relationships. Significant correlations were observed between the number of −OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3′,4′-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents

InVERT molding for scalable control of tissue microarchitecture

Complex tissues contain multiple cell types that are hierarchically organized within morphologically and functionally distinct compartments. Construction of engineered tissues with optimized tissue architecture has been limited by tissue fabrication techniques, which do not enable versatile microscale organization of multiple cell types in tissues of size adequate for physiological studies and tissue therapies. Here we present an ‘Intaglio-Void/Embed-Relief Topographic molding’ method for microscale organization of many cell types, including induced pluripotent stem cell-derived progeny, within a variety of synthetic and natural extracellular matrices and across tissues of sizes appropriate for in vitro, pre-clinical, and clinical studies. We demonstrate that compartmental placement of non-parenchymal cells relative to primary or induced pluripotent stem cell-derived hepatocytes, compartment microstructure, and cellular composition modulate hepatic functions. Configurations found to sustain physiological function in vitro also result in survival and function in mice for at least 4 weeks, demonstrating the importance of architectural optimization before implantation.National Institutes of Health (U.S.) (EB008396)National Institutes of Health (U.S.) (DK56966)National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (1F32DK091007)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (1F32DK095529)National Science Foundation (U.S.). Graduate Research Fellowship Program (1122374

Identification of Genes with Allelic Imbalance on 6p Associated with Nasopharyngeal Carcinoma in Southern Chinese

Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC. In total, 360 subjects and 360 healthy controls were included, and 233 single nucleotide polymorphisms (SNPs) on 6p were examined. Significant single-marker associations were found for SNPs rs2267633 (p = 4.49×10−5), rs2076483 (most significant, p = 3.36×10−5), and rs29230 (p = 1.43×10−4). The highly associated genes were the gamma-amino butyric acid B receptor 1 (GABBR1), human leukocyte antigen (HLA-A), and HLA complex group 9 (HCG9). Haplotypic associations were found for haplotypes AAA (located within GABBR1, p-value  = 6.46×10−5) and TT (located within HLA-A, p = 0.0014). Further investigation of the homozygous genotype frequencies between cases and controls suggested that micro-deletion regions occur in GABBR1 and neural precursor cell expressed developmentally down-regulated 9 (NEDD9). Quantitative real-time polymerase chain reaction (qPCR) using 11 pairs of NPC biopsy samples confirmed the significant decline in GABBR1 and NEDD9 mRNA expression in the cancer tissues compared to the adjacent non-tumor tissue (p<0.05). Our study demonstrates that multiple chromosome 6p susceptibility loci contribute to the risk of NPC, possibly though GABBR1 and NEDD9 loss of function

Structural Analysis of the UBA Domain of X-linked Inhibitor of Apoptosis Protein Reveals Different Surfaces for Ubiquitin-Binding and Self-Association

BACKGROUND: Inhibitor of apoptosis proteins (IAPs) belong to a pivotal antiapoptotic protein family that plays a crucial role in tumorigenesis, cancer progression, chemoresistance and poor patient-survival. X-linked inhibitor of apoptosis protein (XIAP) is a prominent member of IAPs attracting intense research because it has been demonstrated to be a physiological inhibitor of caspases and apoptosis. Recently, an evolutionarily conserved ubiquitin-associated (UBA) domain was identified in XIAP and a number of RING domain-bearing IAPs. This has placed the IAPs in the group of ubiquitin binding proteins. Here, we explore the three-dimensional structure of the XIAP UBA domain (XIAP-UBA) and how it interacts with mono-ubiquitin and diubiquitin conjugates. PRINCIPAL FINDINGS: The solution structure of the XIAP-UBA domain was determined by NMR spectroscopy. XIAP-UBA adopts a typical UBA domain fold of three tightly packed alpha-helices but with an additional N-terminal 3(10) helix. The XIAP-UBA binds mono-ubiquitin as well as Lys48-linked and linear-linked diubiquitins at low-micromolar affinities. NMR analysis of the XIAP-UBA-ubiquitin interaction reveals that it involves the classical hydrophobic patches surrounding Ile44 of ubiquitin and the conserved MGF/LV motif surfaces on XIAP-UBA. Furthermore, dimerization of XIAP-UBA was observed. Mapping of the self-association surface of XIAP-UBA reveals that the dimerization interface is formed by residues in the N-terminal 3(10) helix, helix alpha1 and helix alpha2, separate from the ubiquitin-binding surface. CONCLUSION: Our results provide the first structural information of XIAP-UBA and map its interaction with mono-ubiquitin, Lys48-linked and linear-linked diubiquitins. The notion that XIAP-UBA uses different surfaces for ubiquitin-binding and self-association provides a plausible model to explain the reported selectivity of XIAP in binding polyubiquitin chains with different linkages.published_or_final_versio

Mentoring in palliative medicine in the time of covid-19: a systematic scoping review : Mentoring programs during COVID-19.

IntroductionThe redeployment of mentors and restrictions on in-person face-to-face mentoring meetings during the COVID-19 pandemic has compromised mentoring efforts in Palliative Medicine (PM). Seeking to address these gaps, we evaluate the notion of a combined novice, peer-, near-peer and e-mentoring (CNEP) and interprofessional team-based mentoring (IPT) program.MethodsA Systematic Evidence Based Approach (SEBA) guided systematic scoping review was carried out to study accounts of CNEP and IPT from articles published between 1st January 2000 and 28th February 2021. To enhance trustworthiness, concurrent thematic and content analysis of articles identified from structured database search using terms relating to interprofessional, virtual and peer or near-peer mentoring in medical education were employed to bring together the key elements within included articles.ResultsFifteen thousand one hundred twenty one abstracts were reviewed, 557 full text articles were evaluated, and 92 articles were included. Four themes and categories were identified and combined using the SEBA's Jigsaw and Funnelling Process to reveal 4 domains - characteristics, mentoring stages, assessment methods, and host organizations. These domains suggest that CNEP's structured virtual and near-peer mentoring process complement IPT's accessible and non-hierarchical approach under the oversight of the host organizations to create a robust mentoring program.ConclusionThis systematic scoping review forwards an evidence-based framework to guide a CNEP-IPT program. At the same time, more research into the training and assessment methods of mentors, near peers and mentees, the dynamics of mentoring interactions and the longitudinal support of the mentoring relationships and programs should be carried out

Micro-RNAs as diagnostic or prognostic markers in human epithelial malignancies

Micro-RNAs (miRs) are important regulators of mRNA and protein expression; the ability of miR expression profilings to distinguish different cancer types and classify their sub-types has been well-described. They also represent a novel biological entity with potential value as tumour biomarkers, which can improve diagnosis, prognosis, and monitoring of treatment response for human cancers. This endeavour has been greatly facilitated by the stability of miRs in formalin-fixed paraffin-embedded (FFPE) tissues, and their detection in circulation. This review will summarize some of the key dysregulated miRs described to date in human epithelial malignancies, and their potential value as molecular bio-markers in FFPE tissues and blood samples. There remain many challenges in this domain, however, with the evolution of different platforms, the complexities of normalizing miR profiling data, and the importance of evaluating sufficiently-powered training and validation cohorts. Nonetheless, well-conducted miR profiling studies should contribute important insights into the molecular aberrations driving human cancer development and progression

Differences in the Properties and Mirna Expression Profiles between Side Populations from Hepatic Cancer Cells and Normal Liver Cells

AIMS: Because hepatic cancer stem cells (HCSCs) are believed to derive from the conversion of hepatic normal stem cells (HNSCs), the identification of the differences that distinguish HCSCs from HNSCs is important. METHODS: The HCC model was established in F344 rats by DEN induction. Using FACS analysis, side population cells from HCC (SP-HCCs) were isolated from the epithelial-like cells of HCC tissues, and the side population cells from normal liver (SP-NLCs) were isolated from syngeneic normal liver cells. The expression of stem cell markers was detected in both freshly isolated and amplified subpopulations. After induction with HGF, the differentiation of each subpopulation was analyzed by detection of early and late liver markers. In vivo, the biological characteristics of SP-HCCs and SP-NLCs were analyzed by repairing injured livers or forming tumors in nude mice. In addition, the expression of miRNAs was examined in both populations by miRNA array and QRT-PCR. RESULTS: SP-NLCs and SP-HCCs were 4.30±0.011% and 2.100±0.010% of the whole population, respectively. Both SP-NLCs and SP-HCCs displayed greater expression of stem cell markers (CD133 and EpCAM) than NSP-NLCs and NSP-HCCs, respectively (P<0.01), both after fresh isolation and amplification. Upon HGF induction, SP-NLCs generated many ALB positive cells and few CK-7 positive cells, but NSP-NLCs could generate only ALB positive cells. In contrast, SP-HCCs gave rise to only AFP positive cells. As few as 5 × 10⁵ SP-NLCs were capable of repairing liver injury, while the same number of NSP-NLCs could not repair the liver. Furthermore, only 1 × 10⁴ SP-HCCs were necessary to initiate a tumor, while NSP-HCCs could not form a tumor. Compared to SP-NLCs, 68 up-regulated and 10 down-regulated miRNAs were present in SP-HCCs (P<0.01). CONCLUSION: Based on the decisive roles of some miRNAs in the genesis of HCSCs, miRNAs may contribute to the different characteristics that distinguish SP-HCCs from SP-NLCs