Efficacy of plastinated specimens in anatomy education: A systematic review and meta-analysis.

Plastination, a permanent preservation method for human tissues and organs, is increasingly being used in anatomy education. However, there is a paucity of systematic reviews and meta-analyses summarizing the educational efficacy of plastinated specimens. This meta-analysis compared the assessment scores of students exposed to plastinated specimens against those exposed to other common instructional methods. A systematic search was conducted through four databases, from 2000 to July 2022. Titles and abstracts of the retrieved records were screened according to predetermined eligibility criteria. Of the 159 records screened, 18 were subjected to full-text review. Among the 18 studies, five articles reported post-intervention test scores for intervention (plastinated) and control (other modalities) groups. Studies were subjected to GRADE quality assessment, and four studies with moderate to high ratings were included for meta-analysis. Students' perceptions (n = 15 studies) were qualitatively analyzed using an inductive narrative analysis. No significant effect was detected between the intervention (n = 417) and control groups (n = 422) (standardized mean difference = 0.08; 95% CI [-0.36, 0.52]; p = 0.73). Four themes emerged from students' perceptions: ease of use, motivation to study, spatial understanding, and learning preference. Overall, student performance outcomes comparing the use of plastinated specimens versus other instructional modalities are very limited. This meta-analysis suggests that knowledge gained from plastinated specimens is comparable to learning achieved through other modalities; though this outcome should be interpreted with caution as there is currently insufficient evidence for definitive conclusions.

Morphometry of the sural nerve in diabetic neuropathy: a systematic review.

PURPOSE: The aim of this systematic review is to evaluate the usefulness of sural nerve ultrasonography in diagnosing diabetes mellitus (DM) and diabetic polyneuropathy (DPN), the latter of which is a common long-term complication for diabetic patients that frequently involves the sural nerve. METHODOLOGY: A meta-analysis of the cross-sectional areas (CSAs) of sural nerves in healthy individuals and patients with diabetes mellitus based on a total of 32 ultrasonographic-based studies from 2015 to 2023 was performed. Sub-analyses were performed for factors such as geographical location and measurement site. RESULTS: The meta-analysis showed that the mean CSA of the sural nerve was significantly larger in DM patients with DPN only compared to healthy individuals across all regions and when pooled together. An age-dependent increase in the CSA of healthy sural nerves is apparent when comparing the paediatric population with adults. CONCLUSION: Sural nerve ultrasonography can distinguish diabetic adults with DPN from healthy adults based on cross-sectional area measurement. Future studies are needed to clarify the relationships between other parameters, such as body metrics and age, with sural nerve CSAs. Cut-offs for DPN likely need to be specific for different geographical regions.

What is the evidence for biology as the 'heart of eligibility' to study medicine? A retrospective analysis.

The first, sometimes the only, selection tool for entry into undergraduate medicine is prior educational attainment (PEA). This is often further specified to include certain subjects, for example, biology is a prerequisite for entry into medicine in many Asian countries. However, there seems no clear evidence base for this prerequisite. Our aim, therefore, was to carry out a retrospective quantitative study comparing the performances of five cohorts of students (2015-2019 entry; n = 588) with and without biology PEA in Years 1 and 2 Bachelor of Medicine and Bachelor of Surgery (MBBS) integrated written assessments (n = 3) and anatomy practical examinations (APE) (n = 5). The study was conducted at one of Singapore's three medical schools. Data were analyzed using independent t-tests and Mann-Whitney U with p values of less than 0.05 were considered significant. There were no significant differences in performance on any Years 1 or 2 integrated written assessments. Similarly, in one of the APE, a significant difference was found for one cohort (academic year [AY] 2015-2016) out of five assessments. These results suggest that having a prior biology qualification does not make a difference in assessment performance in the early years of medical school. This information may help stakeholders and admissions committees decide whether biology is required for medical school entrance.

Students' learning experiences of three-dimensional printed models and plastinated specimens: a qualitative analysis.

BACKGROUND: Traditional cadaveric dissection is declining whilst plastinated and three-dimensional printed (3DP) models are increasingly popular as substitutes to the conventional anatomy teaching and learning methods. It is unclear about the pros and cons of these new tools and how they impact students' learning experiences of anatomy including humanistic values such as respect, care and empathy.  METHODS: Ninety-six students' views were sought immediately after a randomized cross-over study. Pragmatic design was used to investigate the learning experiences of using plastinated and 3DP models of cardiac (in Phase 1, n = 63) and neck (in Phase 2, n = 33) anatomy. Inductive thematic analysis was conducted based on 278 free text comments (related to strengths, weaknesses, things to improve), and focus group (n = 8) transcriptions in full verbatim about learning anatomy with these tools. RESULTS: Four themes were found: perceived authenticity, basic understanding versus complexity, attitudes towards respect and care, and multimodality and guidance. CONCLUSIONS: Overall, students perceived plastinated specimens as more real and authentic, thus perceived more respect and care than 3DP models; whereas 3DP models were easy to use and prefered for learning basic anatomy.

UDP-glucose dehydrogenase (UGDH) activity is suppressed by peroxide and promoted by PDGF in fibroblast-like synoviocytes: Evidence of a redox control mechanism.

UDP-glucose dehydrogenase (UGDH) generates essential precursors of hyaluronic acid (HA) synthesis, however mechanisms regulating its activity are unclear. We used enzyme histostaining and quantitative image analysis to test whether cytokines that stimulate HA synthesis upregulate UGDH activity. Fibroblast-like synoviocytes (FLS, from N = 6 human donors with knee pain) were cultured, freeze-thawed, and incubated for 1 hour with UDP-glucose, NAD+ and nitroblue tetrazolium (NBT) which allows UGDH to generate NADH, and NADH to reduce NBT to a blue stain. Compared to serum-free medium, FLS treated with PDGF showed 3-fold higher UGDH activity and 6-fold higher HA release, but IL-1beta/TGF-beta1 induced 27-fold higher HA release without enhancing UGDH activity. In selected proliferating cells, UGDH activity was lost in the cytosol, but preserved in the nucleus. Cell-free assays led us to discover that diaphorase, a cytosolic enzyme, or glutathione reductase, a nuclear enzyme, was necessary and sufficient for NADH to reduce NBT to a blue formazan dye in a 1-hour timeframe. Primary synovial fibroblasts and transformed A549 fibroblasts showed constitutive diaphorase/GR staining activity that varied according to supplied NADH levels, with relatively stronger UGDH and diaphorase activity in A549 cells. Unilateral knee injury in New Zealand White rabbits (N = 3) stimulated a coordinated increase in synovial membrane UGDH and diaphorase activity, but higher synovial fluid HA in only 2 out of 3 injured joints. UGDH activity (but not diaphorase) was abolished by N-ethyl maleimide, and inhibited by peroxide or UDP-xylose. Our results do not support the hypothesis that UGDH is a rate-liming enzyme for HA synthesis under catabolic inflammatory conditions that can oxidize and inactivate the UGDH active site cysteine. Our novel data suggest a model where UGDH activity is controlled by a redox switch, where intracellular peroxide inactivates, and high glutathione and diaphorase promote UGDH activity by maintaining the active site cysteine in a reduced state, and by recycling NAD+ from NADH.

A systematic review: normative reference values of the median nerve cross-sectional area using ultrasonography in healthy individuals.

Median nerve cross-sectional area (CSA) was used for screening and diagnosis of neuropathy, but few studies have suggested reference range. Hence, this systematic review was performed to evaluate a normative values of median nerve CSA at various landmarks of upper limb based on ultrasonography. PubMed and Web of science were used to search relevant articles from 2000 to 2020. Forty-one eligible articles (2504 nerves) were included to access median nerve CSA at different landmarks (mid-arm, elbow, mid-forearm, carpal tunnel (CT) inlet and CT outlet). Data was also stratified based on age, sex, ethnicity, geographical location, and method of measurement. Random effects model was used to calculate pooled weighted mean (95% confidence interval (CI), [upper bound, lower bound]) at mid-arm, elbow, mid-forearm, CT inlet and outlet which found to be 8.81 mm2, CI [8.10, 9.52]; 8.57 mm2 [8.00, 9.14]; 7.07 mm2 [6.41, 7.73]; 8.74 mm2 [8.45, 9.03] and 9.02 mm2 [8.08, 9.95] respectively. Median nerve CSA varies with age, geographical location, and sex at all landmarks. A low (I2 < 25%) to considerable heterogeneity (I2 > 75%) was observed, indicating the variation among the included studies. These findings show that median nerve CSA is varying not only along its course but also in other sub-variables.

A validated instrument measuring students' perceptions on plastinated and three-dimensional printed anatomy tools.

Due to the modernization of the medical curriculum and technological advancements, anatomy education has evolved beyond cadaveric dissection alone. Plastination techniques, three-dimensional (3D) modeling, and 3D printing technologies have progressively gained importance. However, there are limited valid and reliable surveys to evaluate students' perceptions of these new anatomy tools. Hence, this study aimed to develop a validated instrument to measure students' learning satisfaction, self-efficacy, humanistic values, and perceived limitations of plastinated and 3D printed models. A 41-item survey (five-point Likert scale, 1 = strongly disagree to 5 = strongly agree) was administered to Year 1 undergraduate medical students following a randomized controlled crossover study that evaluated plastinated and 3D printed cardiac and neck models. Ninety-six responses were received, and a factor analysis was performed with the Kaiser-Meyer-Olkin sampling adequacy of 0.878. The confirmatory factor analysis yielded a 4-factor, 19 items model that had a good fit with the latent constructs of x 2 (147) = 211.568, P < 0.001, root mean square error of approximation = 0.068, root mean square residual = 0.064, comparative fit index = 0.946, and Tucker Lewis index = 0.937. The Cronbach's alpha for the individual factors ranged from 0.74 to 0.95, indicating good internal consistency. This demonstrated a psychometrically valid and reliable instrument to measure students' perceptions toward plastinated and 3D printed models.

Investigating the effectiveness of three-dimensionally printed anatomical models compared with plastinated human specimens in learning cardiac and neck anatomy: A randomized crossover study.

Three-dimensional printing (3DP) technology has been increasingly applied in health profession education. Yet, 3DP anatomical models compared with the plastinated specimens as learning scaffolds are unclear. A randomized-controlled crossover study was used to evaluate the objective outcomes of 3DP models compared with the plastinated specimens through an introductory lecture and team study for learning relatively simple (cardiac) and complex (neck) anatomies. Given the novel multimaterial and multicolored 3DP models are replicas of the plastinated specimens, it is hypothesized that 3DP models have the same educational benefits to plastinated specimens. This study was conducted in two phases in which participants were randomly assigned to 3DP (n = 31) and plastinated cardiac groups (n = 32) in the first phase, whereas same groups (3DP, n = 15; plastinated, n = 18) used switched materials in the second phase for learning neck anatomy. The pretest, educational activities and posttest were conducted for each phase. Miller's framework was used to assess the cognitive outcomes. There was a significant improvement in students' baseline knowledge by 29.7% and 31.3% for Phase 1; 31.7% and 31.3% for Phase 2 plastinated and 3DP models. Posttest scores for cardiac (plastinated, 3DP mean ± SD: 57.0 ± 13.3 and 60.8 ± 13.6, P = 0.27) and neck (70.3 ± 15.6 and 68.3 ± 9.9, P = 0.68) phases showed no significant difference. In addition, no difference observed when cognitive domains compared for both cases. These results reflect that introductory lecture plus either the plastinated or 3DP modes were effective for learning cardiac and neck anatomy.

Imaging cancer cells with nanostructures: Prospects of nanotechnology driven non-invasive cancer diagnosis.

The application of nanostructured materials in medicine is a rapidly evolving area of research that includes both the diagnosis and treatment of various diseases. Metals, metal oxides and carbon-based nanomaterials have shown much promise in medical technological advancements due to their tunable physical, chemical and biological properties. The nanoscale properties, especially the size, shape, surface chemistry and stability makes them highly desirable for diagnosing and treating various diseases, including cancers. Major applications of nanomaterials in cancer diagnosis include in vivo bioimaging and molecular marker detection, mainly as image contrast agents using modalities such as radio, magnetic resonance, and ultrasound imaging. When a suitable targeting ligand is attached on the nanomaterial surface, it can help pinpoint the disease site during imaging. The application of nanostructured materials in cancer diagnosis can help in the early detection, treatment and patient follow-up . This review aims to gather and present the information regarding the application of nanotechnology in cancer diagnosis. We also discuss the challenges and prospects regarding the application of nanomaterials as cancer diagnostic tools.

Labeling and tracking cells with gold nanoparticles.

Gold nanoparticles (AuNPs) have garnered much attention as contrast agents for computerized tomography (CT) because of their facile synthesis and surface functionalization, in addition to their significant X-ray attenuation and minimal cytotoxicity. Cell labeling using AuNPs and tracking of the labeled cells using CT has become a time-efficient and cost-effective method. Actively targeted AuNPs can enhance CT contrast and sensitivity, and further reduce the radiation dosage needed during CT imaging. In this review, we summarize the state-of-the-art use of AuNPs in CT for cell tracking, including the precautionary steps necessary for their use and the difficulty in translating the process into clinical use.

A Review on Occurrence of Pesticides in Environment and Current Technologies for Their Remediation and Management.

Pesticides are the chemicals used to prevent plant diseases, weeds, pests and to enhance the quality of the food products. The uniqueness of their chemical structure, and/or their interactions with the environment characterize the nature of pesticides. In most scenarios, the end users such as farmers and consumers, who know the serious effects of pesticides cannot translate this awareness into their practice. The mobility, bioavailability of pesticides in soils (atmosphere, water bodies) is based upon their absorption and desorption mechanisms from soil particles. Pesticides have harmful effects in the soil ecosystem, and mankind (which affects biological molecules, tissues, and organs resulting in acute or chronic disorders). It affects humans of all ages including prenatal. These pollutants, when released into the water bodies affects the aquatic systems. The water molecules in the river are affected by the accumulation of these toxic contaminants with its alkaline pH and heavy metals which could adversely affect the health of flora and fauna. This article discusses the scientific literature on various remediation technologies available for the safer use of pesticides. The limitations and benefits of chemically polluted soil using microorganisms and other biological methods have been discussed. However, future development measures are still needed to ensure full implementation of these methods to save the environment.

Real-Time and In-Situ Monitoring of H2O2 Release from Living Cells by a Stretchable Electrochemical Biosensor Based on Vertically Aligned Gold Nanowires.

Traditional electrochemical biosensing electrodes (e.g., gold disk, glassy carbon electrode, etc.) can undergo sophisticated design to detect chemicals/biologicals from cells. However, such electrodes are typically rigid and nonstretchable, rendering it challenging to detect cellular activities in real-time and in situ when cells are in mechanically deformed states. Here, we report a new stretchable electrochemical cell-sensing platform based on vertically aligned gold nanowires embedded in PDMS (v-AuNWs/PDMS). Using H2O2 as a model analyte, we show that the v-AuNWs/PDMS electrode can display an excellent sensing performance with a wide linear range, from 40 µM to 15 mM, and a high sensitivity of 250 mA/cm2/M at a potential of -0.3 V. Moreover, living cells can grow directly on our stretchable high-surface area electrodes with strong adhesion, demonstrating their excellent biocompatibility. Further cell stimulation by adding chemicals induced H2O2 generation, which can be detected in real-time and in situ using our v-AuNWs/PDMS platform for both natural and stretched states of cells. Our results indicate the v-AuNWs/PDMS electrochemical biosensor may serve as a general cell-sensing platform for living organisms under deformed states.

Pellino1 specifically binds to phospho-Thr18 of p53 and is recruited to sites of DNA damage.

Pellino1 is an E3 ubiquitin ligase that plays a key role in positive regulation of innate immunity signaling, specifically required for the production of interferon when induced by viral double-stranded RNA. We report the identification of the tumor suppressor protein, p53, as a binding partner of Pellino1. Their interaction has a Kd of 42 ±â€¯2 µM and requires phosphorylation of Thr18 within p53 and association with the forkhead-associated (FHA) domain of Pellino1. We employed laser micro-irradiation and live cell microscopy to show that Pellino1 is recruited to newly occurring DNA damage sites, via its FHA domain. Mutation of a hitherto unidentified nuclear localization signal within the N-terminus of Pellino1 led to its exclusion from the nucleus. This study provides evidence that Pellino1 translocates to damaged DNA in the nucleus and has a functional role in p53 signaling and the DNA damage response.

Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms.

A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K1 and K2) and the coefficient of viscosity (µ). This difference was more pronounced for cancer cells after 48h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach.

Bioreducible PEI-functionalized glycol chitosan: A novel gene vector with reduced cytotoxicity and improved transfection efficiency.

Non-viral gene delivery has been well recognised as a potential way to address the main safety limitations of viral gene carriers. A new redox-responsive PEI derivative was designed, synthesized and evaluated for non-viral delivery applications of GFP DNA. Glycol chitosan was covalently attached to highly branched LMW PEI via bio-cleavable disulfide bonds to synthesize a new redox-responsive gene carrier (GCS-ss-PEI). Results showed the enhanced buffering capacity of GCS-ss-PEI, 43.1%, compared to the buffering capacities of both LMW PEI and HMW PEI, 23.2% and 31.5%, respectively, indicating more likely endosomal escape of the entrapped gene for GCS-ss-PEI. Moreover, electrophoretic gel retardation assay, performed to investigate the binding strength of GCS-ss-PEI to GFP DNA, showed stronger complexation with GFP DNA in GCS-ss-PEI at non-GSH condition. Employing GCS and incorporation of disulfide bonds in the structure of the PEI-based gene carrier resulted in improved redox-responsivity, reduced toxicity, enhanced endosomal escape and GFP DNA transfection. The facilitated intracellular gene release along with excellent redox-responsive characteristics and dropped cytotoxicity suggests the potential of GCS-ss-PEI as a candidate for developing highly efficient and safe gene vectors.

Tumor cell-specific photothermal killing by SELEX-derived DNA aptamer-targeted gold nanorods.

Despite widespread availability of cytotoxic chemotherapeutic agents, the killing of tumour cells without affecting healthy surrounding tissue remains elusive, although recent developments in terms of plasmonic nanoparticles capable of photothermal killing have some promise. Here we describe novel DNA aptamer-tethered gold nanorods (GNRs) that act as efficient photothermal therapeutics against tumour cells, but not their isogenic normal cell counterparts. A modified Cell-SELEX process was developed to select a novel DNA aptamer (KW16-13) that specifically recognised and was internalised by cells of the MCF10CA1h human breast ductal carcinoma line but not by those of its isogenic normal counterpart (MCF10A). GNRs conjugated to KW16-13 were readily internalized by the MCF10CA1h tumour cells with minimal uptake by MCF10A normal cells. Upon near infrared (NIR) light irradiation, tumour cell death of >96%, could be effected, compared to <1% in the normal cells or cells incubated with GNRs alone, our KW16-13 aptamer-targeted GNRs thus showing >71-fold tumor cell death than GNRs-targeted with a previously described aptamer. This demonstrates the significant potential for aptamer functionalised-GNRs to be used effective and above all selective anti-cancer photothermal therapeutics.

Dimerization of flavivirus NS4B protein.

UNLABELLED: Flavivirus replication is mediated by a complex machinery that consists of viral enzymes, nonenzymatic viral proteins, and host factors. Many of the nonenzymatic viral proteins, such as NS4B, are associated with the endoplasmic reticulum membrane. How these membrane proteins function in viral replication is poorly understood. Here we report a robust method to express and purify dengue virus (DENV) and West Nile virus NS4B proteins. The NS4B proteins were expressed in Escherichia coli, reconstituted in dodecyl maltoside (DDM) detergent micelles, and purified to >95% homogeneity. The recombinant NS4B proteins dimerized in vitro, as evidenced by gel filtration, chemical cross-linking, and multiangle light scattering experiments. The dimeric form of NS4B was also detected when the protein was expressed alone in cells as well as in cells infected with DENV type 2 (DENV-2). Mutagenesis analysis showed that the cytosolic loop (amino acids 129 to 165) and the C-terminal region (amino acids 166 to 248) are responsible for NS4B dimerization. trans-Complementation experiments showed that (i) two genome-length RNAs containing distinct NS4B lethal mutations could not trans-complement each other, (ii) the replication defect of NS4B mutant RNA could be restored in cells containing DENV-2 replicons, and (iii) expression of wild-type NS4B protein alone was not sufficient to restore the replication of the NS4B mutant RNA. Collectively, the results indicate that trans-complementation of a lethal NS4B mutant RNA requires wild-type NS4B presented from a replication complex. IMPORTANCE: The reported expression and purification system has made it possible to study the biochemistry and structure of flavivirus NS4B proteins. The finding of flavivirus NS4B dimerization and the mapping of regions important for NS4B dimerization provide the possibility to inhibit viral replication through blocking NS4B dimerization. The requirement of NS4B in the context of the replication complex for successful trans-complementation enhances our understanding of NS4B in flavivirus replication.

A crystal structure of the dengue virus non-structural protein 5 (NS5) polymerase delineates interdomain amino acid residues that enhance its thermostability and de novo initiation activities.

The dengue virus (DENV) non-structural protein 5 (NS5) comprises an N-terminal methyltransferase and a C-terminal RNA-dependent RNA polymerase (RdRp) domain. Both enzymatic activities form attractive targets for antiviral development. Available crystal structures of NS5 fragments indicate that residues 263-271 (using the DENV serotype 3 numbering) located between the two globular domains of NS5 could be flexible. We observed that the addition of linker residues to the N-terminal end of the DENV RdRp core domain stabilizes DENV1-4 proteins and improves their de novo polymerase initiation activities by enhancing the turnover of the RNA and NTP substrates. Mutation studies of linker residues also indicate their importance for viral replication. We report the structure at 2.6-Å resolution of an RdRp fragment from DENV3 spanning residues 265-900 that has enhanced catalytic properties compared with the RdRp fragment (residues 272-900) reported previously. This new orthorhombic crystal form (space group P21212) comprises two polymerases molecules arranged as a dimer around a non-crystallographic dyad. The enzyme adopts a closed "preinitiation" conformation similar to the one that was captured previously in space group C2221 with one molecule per asymmetric unit. The structure reveals that residues 269-271 interact with the RdRp domain and suggests that residues 263-268 of the NS5 protein from DENV3 are the major contributors to the flexibility between its methyltransferase and RdRp domains. Together, these results should inform the screening and development of antiviral inhibitors directed against the DENV RdRp.

Structure of human Rack1 protein at a resolution of 2.45†Å.

The crystal structure of human receptor for activated C-kinase 1 (hRack1) protein is reported at 2.45 Šresolution. The crystals belongs to space group P4(1)2(1)2, with three molecules per asymmetric unit. The hRack1 structure features a sevenfold ß-propeller, with each blade housing a sequence motif that contains a strictly conserved Trp, the indole group of which is embedded between adjacent blades. In blades 1-5 the imidazole group of a His residue is wedged between the side chains of a Ser residue and an Asp residue through two hydrogen bonds. The hRack1 crystal structure forms a starting basis for understanding the remarkable scaffolding properties of this protein.